Endocrinology, Diabetes & Metabolism Research
The Division of Endocrinology, Diabetes, and Metabolism at Upstate Medical University is at the forefront of cutting-edge research, engaging in both clinical and laboratory investigations aimed at advancing our understanding of diabetes mellitus and its related complications. Our researchers put a strong focus on diabetes prevention and management strategies. Our faculty also conducts robust quality improvement projects and studies related to thyroid, pituitary, adrenal, and other endocrine disorders. With a dedicated team of researchers and physicians, the division remains committed to paving the way for improved patient care and outcomes.
Faculty Interested in Research
- Dr. Runa Acharya
- Dr. Oleg Chepurny
- Dr. Tuncay Delibasi
- Dr. Barbara Feuerstein
- Dr. George Holz
- Dr. Rachel Hopkins
- Dr. Roberto Izquierdo
- Dr. Ruth S. Weinstock
- Dr. Malek El Muayed
Publications
Ongoing Clinical Research
The Endocrine and Diabetes Clinical Research Center at Upstate Institute for Human Performance is active in numerous clinical research studies related to the prevention and management of type 1 and type 2 diabetes in addition to its complications in children and adults. For more information call (315) 464-9012.
Through these research studies, University Endocrinologists are able to offer individuals with diabetes the advantage of the latest investigational and new pharmacologic treatments, state-of-the-art medical procedures and testing, and close, specialized medical attention. In addition, these services are often provided free to study volunteers. The conduct of research trials can also provide you with more information and a better understanding of your medical condition.
Clinical Research Team
- Ruth Weinstock, MD, PhD
- Suzan Bzdick, RN, CDE, CCRC, Supervisor, Endocrine Research Team
- Sri Laxmi Veerapaneni MD, MSc, Clinical Research Coordinator
- Lynn Agostini, Clinical Research Coordinator
- Jane Bulger, MS, CCRC, Clinical Research Coordinator
- Sarah Doolittle, BS, CCRC, Clinical Research Coordinator
- David Hansen, MD, MPH
- Roberto E Izquierdo, MD
- Angela P Mojica Sanabria, MD
- Dr. Malek El Muayed
- Dr. Tuncay Delibasi
Being a Volunteer
Find a Study: Diabetes Clinical Trials
Volunteering to participate in a clinical research study is one of the best ways you can contribute to the understanding of diseases that affect people and the development of new therapies. As a volunteer, you are the most critical link in a long chain of research and testing in the development of new medications.
Clinical Research Trial
Each year, thousands of people volunteer to participate in clinical drug studies. Benefits as a volunteer may include:
- Receiving medical care from physicians during a study.
- Learning new information about your condition.
- Participation in clinical trials may lead to new therapies.
- Compensation is often offered for time and travel.
Volunteering to participate in a clinical drug study is one of the best ways YOU can contribute to the understanding of diseases that affect people and the development of new therapies.
Ongoing Laboratory Research
The Islet Biology group is comprised of the laboratories of Dr. George G. Holz, Dr. Tuncay Delibasi, and Dr. Malek El Muayed, located at the Institute for Human Performance. Ongoing studies seek to identify processes of pancreatic beta-cell insulin secretion, differentiation, proliferation, and survival that are under the control of nutrients, incretin hormones, or pharmaceuticals. Translational research activities include a small molecule drug discovery program that should facilitate the treatment of type 2 diabetes mellitus in humans.
Selected Publications of Dr. Holz
2023
- A peptide triple agonist of GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors promotes glycemic control and weight loss.
Scientific Reports, 2023
This study performed in collaboration with the Doyle laboratory at Syracuse University evaluated the pharmacological properties of a novel unimolecular triple agonist that reduces blood glucose and body weight by simultaneously stimulating GLP-1, NPY1R, and NPY2R receptors. - Excess pancreatic elastase alters acinar-beta-cell communication by impairing the mechano-signaling and the PAR2 pathways.
Cell Metabol., 2023
This study performed in collaboration with the Kulkarni laboratory at the Joslin Diabetes Center in Boston established a novel Protease-Activated Receptor-2 (PAR2) mediated form of intra-pancreatic communication in which elastase secreted from pancreatic acinar cells influences the growth, survival, and function of pancreatic beta cells. - Corrination mitigates peptide aggregation as exemplified by Glucagon.
Peptides, 2023
This study performed in collaboration with the Doyle laboratory at Syracuse University established that the physiochemical properties of glucagon are stabilized by its covalent modification (corrination) with the Vitamin B12 precursor cobinamide (cbi), thereby conferring enhanced solubility and thermostability to glucagon. Potentially, corrination will be a broadly applicable chemistry with which to enhance the actions of numerous systemically administered hormones and neuropeptides.
2022
- Intra-islet glucagon confers beta-cell glucose competence for first-phase insulin secretion and favors GLP-1R stimulation by exogenous glucagon.
J. Biol. Chem., 2022
This was a collaborative study of the Holz lab with Dr. Over Cabrera of Eli Lilly Inc. and Frank Schwede of Biolog Life Sci. using islet perifusion technology developed by Felipe Echeverri and co-workers at Biorep Technologies. The study is noteworthy in that we reported that defective intra-islet glucagon action most likely contributes to the characteristic loss of first-phase insulin secretion measured in an intravenous glucose tolerance test (IVGTT) that is predictive of type 2 diabetes in the clinical setting. - The alpha-7 nicotinic acetylcholine receptor agonist GTS-21 engages the glucagon-like peptide-1 incretin hormone axis to lower levels of blood glucose in db/db mice.
Diabetes, Obesity and Metabolism, 2022.
This R01 funded joint project of the SUNY Upstate G.G. Holz and R.N. Cooney laboratories led to the discovery of novel in vivo blood glucose-lowering properties of the alpha-7 nAChR agonist GTS-1 that stimulates GLP-1 release from intestinal enteroendocrine cells. - Nonpeptide Z360-analogs tagged with trivalent radiometals as anti-CCKR cancer theranostic agents: a preclinical study.
Pharmaceutics, 2022.
This collaborative nuclear medicine study with Professor Theodosia Maina of the University of Athens, Greece led to optimization a theranostics strategy that targets tumors in which there is high-level aberrant expression of the cholecystokinin subtype-2 receptor isoform (CCK2R). - GTS-21, a selective alpha7 nicotinic acetylcholine receptor agonist, ameliorates diabeteic nephropathy in Lepr db/db mice.
Scientific Reports, 2022.
This R01 funded study of the Holz and Cooney labs at SUNY led to our discovery of a beneficial action of GTS-21 to counteract diabetic nephropathy, as studied in obese hyperglycemic mice with defective leptin receptor signaling.
2021
- Design and evaluation of peptide dual-agonists of GLP-1 and NPY2 receptors for glucoregulation and weight loss with mitigated nausea and emesis.
J. Med. Chem., 2021
This study achieved optimization of synthetic hybrid peptides with dual agonist activity at GLP-1 and NPY2 receptors. Blood glucose-lowering and appetite suppressing effects of a newly synthesized GEP44 were measurable in vivo, with increased potency relative to the original lead compound EP45. Synthesis and characterization of GEP44 constituted doctoral thesis work of Brandon T. Milliken working in the laboratory of Dr. Robert P. Doyle at Syracuse University, in collaboration with Drs. Holz and Chepurny at SUNY Upstate. - Synthesis, optimization, and biological evaluation of corrinated conjugates of the GLP-1 agonist exendin-4.
J. Med. Chem., 2021
This study identified a dicyanocobinamide (Cbi) conjugate of the GLP-1R agonist exendin-4 that lowers levels of blood glucose, and that exhibits improved binding and agonist activity at the GLP-1R, while also retaining a preferential biodistribution in the peripheral circulation, but not in the brain. Thus, Cbi-exendin-4 is an attractive option for use in the treatment of type-2 diabetes, without the undersirable side effects of nausea and vomiting. Synthesis and characterization of Cbi-exendin-4 derivatives constituted doctoral thesis work of Ian C. Tinsley working in the laboratory of Dr. Robert P. Doyle at Syracuse University, in collaboration with Drs. Holz and Chepurny at SUNY Upstate. - Cyclic AMP-dependent activation of ERK via GLP-1 receptor signalling requires the neuroendocrine cell-specific guanine nucleotide exchanger NCS-RapGEF2.
J. Neuroendocrinol., 2021
Our collaboration with Drs. Lee E. Eiden and Andrew C. Emery of the Section of Molecular Neuroscience, National Institute of Mental Health, led to the unexpected discovery that NCS-RapGEF2 mediates GLP-1R stimulated activity of the Extracellular Signal-Regulated Kinase (ERK; a.k.a. MAPKK) in an insulin secreting beta-cell line (INS-1). This finding expands the downstream targets of GLP-1 and cAMP to not only PKA and Epac2, but also NCS-RapGEF2. - Synthesis, in vitro biological investigation, and molecular dynamics simulations of thiazolopyrimidine based compounds as corticotrophin releasing factor receptor-1 antagonists.
Bioorganic Chem., 2021
This drug discovery research concerning new small molecule CRFR1 antagonists resulted from the Holz laboratory’s ongoing medicinal chemistry collaborations with an international team of investigators located in Cairo, Sadat City, Alexandria, Athens, and Heraklion.
2020
- FRET assays for cAMP and calcium in a 96-well format using genetically encoded biosensors expressed in living cells.
Bio-protocol, 2020
This protocol provides details concerning FRET assay technology developed by Dr. Oleg G. Chepurny in the Holz laboratory. Graduate student Brandon Milliken in the Doyle laboratory at Syracuse University created two embedded videos in this protocol’s PDF file that explain how to program a Flexstation 3 for FRET assays. - Corrination of a GLP-1 receptor agonist for glycemic control without emesis.
Cell Reports, 2020
This is a study of the Holz and Doyle labs with Dr. Matthew R. Hayes and colleagues at the University of Pennsylvania. It concerns a novel conjugation chemistry that is tailored to direct a GLP-1 analog to the peripheral circulation to stimulate insulin secretion, but not to the central nervous system so that the side effects of nausea and vomiting are minimized. - [99mTc]Tc-DGA1, a promising CCK2R‑ antagonist-based tracer for tumor diagnosis with single-photon emission computed tomography.
Molecular Pharmaceutics, 2020
This collaborative study organized by Prof. Theodosia Maina of the University of Athens, Greece allowed the Holz laboratory to exploit its expertise in molecular pharmacology to validate the
GPCR activating properties of a novel CCK2R antagonist for use in tumor detection using SPECT. - Therapeutic potential of α7 nicotinic acetylcholine receptor agonists to combat obesity, diabetes, and inflammation.
Reviews in Endocrine and Metabolic Disorders, 2020
Based on our own studies and also published literature, the Holz and Cooney laboratories at Upstate advanced a novel hypothesis concerning the etiology of the metabolic syndrome in which defective vagovagal reflexes are a principal driving factor. - Discovery of a stable tripeptide targeting the N-domain of CRF1 receptor.
Amino Acids, 2020.
Collaborative teamwork led by Drs. George Liapakis and Thomas Mavromoustakos allowed discovery of the novel orthosteric CRF1 receptor antagonist (R)-LMI comprised of a Leu, Met, Ilu tripeptide targeting the N-domain of CRF1 receptors. This discovery offers a new pharmacological approach to treating CRF1 receptor-related diseases.
2019
- A-kinase regulator runs amok to provide a paradigm shift in cAMP signaling.
Journal of Biological Chemistry, 2019
This is an Editor's Pick Highlight concerning the published JBC paper of Adame-Garcia et al. (2019) for which the Holz laboratory provided a commissioned commentary. - Nonconventional glucagon and GLP-1 receptor agonist and antagonist interplay at the GLP-1 receptor revealed in high-throughput assays for cAMP.
Journal of Biological Chemistry, 2019
This collaborative study using computational molecular modeling and FRET-based assays for cAMP revealed the promiscuous nature of glucagon and GLP-1 receptor agonist and antagonist action at family B GPCRs.
2018
- A Vitamin B12 Conjugate of Exendin-4 Improves Glucose Tolerance Without Associated Nausea or Hypophagia in Rodents.
Diabetes Obesity Metabolism, 2018
This study reveals that the GLP-1 receptor agonist Exendin-4 can be conjugated to vitamin B12 so that its bioavailability favors a glucoregulatory effect at the pancreas rather than a C.N.S. mediated effect to induce nausea. This is an important finding because nausea is commonly observed in T2DM patients administered unconjugated Exendin-4. Evidently, B12 conjugation reduces the ability of Exendin-4 to penetrate the blood-brain barrier, thereby limiting its access to the C.N.S. This study originated as an inter-institutional collaboration of Dr. Holz with the laboratories of Drs. Robert P. Doyle (Syracuse University), Christian L. Roth (University of Washington) and Matthew R. Hayes (University of Pennsylvania). - Chimeric Peptide EP45 as a Dual Agonist at GLP-1 and NPY2R Receptors.
Scientific Reports, 2018
Reported here are “dual agonist” GPCR-activating properties of the chimeric peptide EP45 that incorporates amino acid motifs found within the blood glucose-lowering agent GLP-1 and the appetite-suppressing agent Peptide YY. Such dual-agonist properties of EP45 were validated in a new FRET assay developed at the Holz laboratory by Dr. Oleg G. Chepurny working in collaboration with Dr. Robert P. Doyle of the Syracuse University Chemistry Department. EP45 was designed by Dr. Doyle working with Syracuse University graduate student Ron L. Bonaccorso. Chimeric peptides such as EP45 are predicted to be of use for simultaneous treatment of diabetes and obesity. - a7 Nicotinic Acetylcholine Receptor Regulates the Function and Viability of L Cells
Endocrinology, 2018
This study was a collaboration with the laboratory of Dr. Robert N. Cooney of the Department of Surgery at SUNY Upstate in which the Holz laboratory participated in the discovery that the a7 nicotinic acetylcholine receptor is a pentameric cation channel that mediates stimulatory effects of GTS-21 on enteroendocrine L-cell GLP-1 release. - Restoration of Glucose-Stimulated Cdc42-Pak1 Activation and Insulin Secretion by a Selective Epac Activator in Type 2 Diabetic Human Islets.
Diabetes, 2018
Reported here are collaborative studies of the Holz and Thurmond labs working with Dr. Frank Schwede of the BIOLOG Life Sciences Institute to establish that in human islets from T2DM donors, the Epac selective cAMP analog 8-pCPT-2’-O-Me-cAMP-AM enables F-acting cytoskeletal remodeling so that insulin secretion is restored. - High-Throuput Assays For cAMP Enable GPCR Agonist Drug Discovery
G.G. Holz Seminar Presentation at the IMBB-FORTH Institute of Molecular Biology and Biotechnolgy, Heraklion, Crete, Hellas; By the Invitation of Professor George Liapakis.
2017
- High-Throughput FRET Assays for cAMP Using the Epac1-based Biosensor H188 Enable GPCR Agonist Drug Discovery.
Journal of General Physiology, 149(9):6A 2017
Holz laboratory methodology concerning high-throughput FRET assays in a 96-well format are included in these Abstract and Poster presentations for the 71st Annual Meeting of the Society of General Physiologists "The Optical Revolution in Physiology: From Membrane to Brain" held at Woods Hole, MA in the fall of 2017.
research/laboratory-research/Holz_SGP_Poster_20171.pptx
2016
- Modeling Analysis of Inositol 1,4,5-Trisphosphate Receptor-Mediated Ca2+ Mobilization Under The Control Of Glucagon-Like Peptide-1 In Mouse Pancreatic Beta-Cells.
Amer. J. Physiol. Cell Physiol. 2016
This mathematical modeling paper concerns a collaboration of the Holz laboratory with Japanese investigators Yukari Takeda, Takao Shimayoshi, and Akinori Noma. The mathematical simulation studies provide insight concerning the findings originally reported by Kang, Holz, and co-workers in their 2005 paper published in the Journal of Physiology (A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic beta cells) when the Holz laboratory was based at New York University School of Medicine. - GPR119 Agonist AS1269574 Activates TRPA1 Cation Channels To Stimulate GLP-1 Secretion.
Molecular Endocrinology,2016
In studies of enteroendocrine cell lines, we find that the GPR119 agonist AS1269574 stimulates GLP-1 secretion in a surprisingly TRPA1 cation channel-mediated manner. However, AS1269574 also acts via GPR119 to stimulate proglucagon gene expression. Therefore, AS1269574 possesses unique “dual agonist” properties so that it promotes both GLP-1 release and GLP-1 biosynthesis. - Solution Structure and Constrained Molecular Dynamics Study of Vitamin B12 Conjugates of the Anorectic Peptide PYY(3-36).
ChemMedChem, 2016
This paper provides detailed structural and functional information concerning a Vitamin B12 conjugate of PYY(3-36) that was synthesized in the laboratory of Prof. Robert P. Doyle at the Syracuse University Department of Chemistry. The paper completes the thesis project of Syracuse University graduate Kelly E. Henry who spent time working in the Holz lab to validate this peptide's receptor activating properties. - PI3 Kinases p110alpha And PI3K-C2beta Negatively Regulate cAMP Via PDE3/8 To Control Insulin Secretion In Mouse And Human Islets.
Molecular Metabolism, 2016
This paper highlights our use of the new cAMP antagonist Rp-8-Br-cAMPS-pAB to demonstrate that cAMP-dependent insulin secretion is under the inhibitory control of phosphatidylinositol 3-kinase in pancreatic beta cells. The project was a collaboration with the laboratory of Dr. Patrick E. MacDonald of the University of Alberta, Canada. - Synthetic Small Molecule GLP-1 Secretagogues Prepared By Means Of A Three-Component Indole Annulation Strategy.
Scientific Reports, 2016
In a collaboration with Dr. Jimmy Wu of the Dartmouth College Chemistry Department, we identified the cycloalka[b]indole JWU-A021 to be a potent GLP-1 secretagogue with TRPA1 cation channel activating properties in the intestinal L-cells. The chemistry underlying the synthesis of JWU-A021 provides a new approach to combinatorial small molecule library construction for drug discovery efforts. - George G Holz Model of Beta-Cell Stimulus-Secretion Coupling Version 2
Research Gate, 2016
Illustrated is Version 2 of the Holz laboratory model of pancreatic beta-cell stimulus-secretion coupling. Incorporated into Version 2 are two new features: 1) the role of soluble adenylyl cyclase (sAC) as a mediator of glucose metabolism-stimulated cAMP production, and 2) the role of cAMP as a stimulus for Cdc42-Pak1 activation and cortical F-actin remodeling with consequent mobilization of a reserve pool (RP) of secretory granules to the plasma membrane for insulin exocytosis. Additional abbreviations: RRP, readily-releasable pool; GK, glucokinase; CA, carbonic anhydrase; GLP-1, glucagon-like peptide-1; G pro., G protein; tmAC, transmembrane adenylyl cyclase; Epac2, type 2 isoform of the guanine nucleotide exchange factor directly activated by cAMP; PKA, cAMP-dependent protein kinase; PDE, cyclic nucleotide phosphodiesterase; K-ATP, ATP-sensitive potassium channel; VDCC, voltage-dependent calcium channel; NSCC, non-selective cation channel; Kv, voltage-activated potassium channel; Kca; calcium-activated potassium channel; SERCA, sarcoendoplasmic reticulum calcium transporter; IP3R, inositol trisphosphate receptor; RYR, ryanodine receptor.
All rights reserved:
GGHolz Beta Cell GSIS Version2
DOI:10.13140/RG.2.2.35500.46724 11/2016, DOI: 10.13140/RG.2.2.35500.46724 - George G Holz High Throughput FRET Assays for Detection of cAMP
Research Gate, 2016
Illustrated is Version 2 for Holz Lab Protocols concerning high throughput FRET-based detection of cAMP in a 96-well format. The assay uses the 4th generation Epac1 biosensor H188 invented by the Jalink lab (Klarenbeek 2015; PLOS One). HEK293 cell clones stably expressing this biosensor were created in the Holz lab by Dr. Oleg G. Chepurny. The assay takes advantage of cAMP analogs provided by Dr. Frank Schwede of the Biolog Life Science Institute. Specific details of the assay are to be found in: Holz GG, Leech CA, Roe MW, Chepurny OG. High-throughput FRET assays for fast time-dependent detection of cyclic AMP in pancreatic beta cells. "Cyclic Nucleotide Signaling". Xiaodong Cheng, ed. Taylor and Francis Group. CRC Press, 2015; 35-60.
All rights reserved:
GGHolz High Throughput FRET cAMP Version2
DOI: 10.13140/RG.2.2.35097.42088 11/2016,DOI: 10.13140/RG.2.2.35097.42088
2015
- Molecular Basis of cAMP Signaling in Pancreatic Beta Cells
Chapter 25, Islets of Langerhans, 2nd Edition, 2015
This review commissioned by Springer is Chapter 25 of the Second Edition of the Islets of Langerhans with Md. Shahidul Islam of the Karolinska Institute serving as Editor. - Vitamin B12 Conjugation of Peptide-YY(3-36) Decreases Food Intake Compared to Native Peptide-YY(3-36) Upon Subcutaneous Administration in Male Rats
Endocrinology, 2015
This paper concerns a collaboration of the Holz laboratory with Dr. Robert P. Doyle of Syracuse University's Department of Chemistry and it is the first to demonstrate that increased bioavailability of a subcutaneously administered peptide can be achieved through the use of Vitamin B12 conjugation chemistry. The published findings are the basis of a PhD thesis project of Syracuse University graduate student Kelly E. Henry. - High-Throughput FRET Assays for Fast Time-Dependent Detection of cAMP in Pancreatic Beta Cells
Chapter 3, Cyclic Nucleotide Signaling, 2015
This review describes the details of a novel FRET-based assay for use in the detection of cAMP that was developed starting in 2009 (Chepurny et al. JBC, 2009) in the Holz laboratory for use in studies of GPCR activation. - Rp-cAMPS Prodrugs Reveal the cAMP-Dependence of First-Phase Glucose-Stimulated Insulin Secretion
Molecular Endocrinology, 2015
This research paper describes the synthesis and characterization of highly membrane permeable cAMP analogs that are bioactivatable prodrugs and that act as potent antagonists of PKA and Epac signaling in living cells. In studies of human and rat islets of Langerhans, one such antagonist (Rp-8-Br-cAMPS-pAB) is shown to be a selective inhibitor of first-phase glucose-stimulated insulin secretion. This finding resolves a 40-year debate concerning whether or not cAMP signaling is essential in order for glucose alone to stimulate insulin secretion. - Enhanced Peptide Stability Against Protease Digestion Induced by Intrinsic Factor Binding of a Vitamin B12 Conjugate of Exendin-4.
Molecular Pharmaceutics, 2015
Intrinsic factor (IF) is secreted by parietal cells of the stomach, and it mediates intestinal absorption of dietary Vitamin B12. Potentially, a B12-Exendin-4 conjugate would be an orally administrable GLP-1 receptor agonist by virtue of its ability to bind IF so that intestinal absorption would be facilitated. However, proteolytic digestion of Exendin-4 within the intestine might lead to inactivation of the conjugate. This paper revealed that binding of B12-Exendin-4 to IF conferred a protective effect against protease digestion. The published findings are the basis of a PhD thesis project of Syracuse University graduate student Ron L. Bonaccorso.
2014
- New Insights Concerning the Molecular Basis for Defective Glucoregulation in Soluble Adenylyl Cyclase Knockout Mice
Biochimica et Biophysica Acta Molecular Basis of Disease 2014
This review is one chapter of a Special Issue of BBA organized by Drs. Lonny Levin and Jochen Buck of Cornell University serving as guest Editors. - Regulation of glucose homeostasis by GLP-1
Progress in Molecular Biology and Translational Science 2014
This review summarizes the current state of knowledge regarding how GLP-1 influences systemic glucose homeostasis in humans with type 2 diabetes and in various animal models of type 2 diabetes. Also provided is an update concerning GLP-1 based drug development strategies that target the GLP-1 receptor or DPP-IV in order to lower levels of blood glucose.
2013
- Identification and characterization of small molecules as potent and specific EPAC2 antagonists.
Journal of Medicinal Chemistry 2013
This paper describes the synthesis and properties of novel small molecule Epac2 antagonists including HJC0350. The specificity of these antagonists was evaluated by the Holz lab in FRET-based assays of Epac2 activation. The work was a collaboration of the Holz laboratory with Drs. Chen, Tsalkova, Mei, Cheng, and Zhou of the University of Texas Medical Branch in Galveston, TX. - Synthesis, characterization and pharmacodynamics of vitamin-B12-conjugated glucagon-like peptide-1.
Chem Med Chem 2013
Vitamin B12 conjugates of GLP-1 are under investigation as orally administrable blood glucose-lowering agents. These conjugates bind to gastric instrinsic factor and undergo intestinal absorption using the body's own B12 uptake mechanism. For this study, the Holz laboratory collaborated with Dr. Robert P. Doyle of the Syracuse University Department of Chemistry in a thesis project of SU graduate student Susan Clardy-James. - Epac2 makes a new impact in beta-cell biology.
Diabetes 2013
This invited Commentary summarizes findings demonstrating that under conditions of insulin resistance induced by a high fat diet, the global knockout of Epac2 gene expression leads to beta-cell decompensation that is measurable as defective glucose-stimulated insulin secretion in mice. The Commentary concerns findings published by the laboratory of Dr. Mehboob A. Hussain at Johns Hopkins University School of Medicine (Song et al., Diabetes, 2013). - Stimulation of proglucagon gene expression by human GPR119 in enteroendocrine L-cell line GLUTag.
Molecular Endocrinology 2013
The Holz laboratory collaborated with the laboratories of Dr. Friedrich W. Herberg (Kassel, Germany) and Xiaodong Cheng (Galveston, TX) in order to demonstrate that the fatty acid amide receptor GPR119 stimulates proglucagon gene expression, a necessary first step in GLP-1 biosynthesis. In this study, a new 6-Bn-cAMP-AM analog developed by the BIOLOG Life Sci. Inst. (Bremen, Germany) was also demonstrated to be a selective activator of proglucagon gene expression under the control of RII alpha/beta regulatory subunits of PKA. - Carbon dioxide/bicarbonate and calcium-regulated soluble adenylyl cyclase as a physiological ATP sensor.
Journal of Biological Chemistry 2013
Soluble adenylyl cyclase (sAC) expressed in pancreatic beta cells can generate cAMP in response to an elevation of blood glucose concentration. The glucose-dependence of sAC activity is explained by its coordinate activation in response to glucose-derived metabolic coupling factors (bicarbonate ion, calcium, ATP). We also find that sAC is an intermediary linking beta-cell glucose metabolism to islet insulin secretion. This paper constituted a collaboration of the Holz laboratory with the laboratories of Drs. Lonny Levin, Jochen Buck, and Geoffrey W.G. Sharp of Cornell University. - Leptin-stimulated K-ATP channel trafficking: a new paradigm for beta-cell stimulus-secretion coupling?
Islets 2013
Park et al. (PNAS 2013) find that leptin stimulates AMPK in order to promote K-ATP channel trafficking from cytosolic vesicles to the plasma membrane of beta cells. Such findings provide an unexpected explanation for the earlier report of Kieffer et al. (Diabetes 1997) demonstrating increased K-ATP channel current and reduced insulin secretion in response to leptin. Conceivably, K-ATP channel trafficking can operate in a reverse mode in order to promote depolarization-induced insulin secretion. For example, high concentrations of glucose may suppress AMPK activity, thereby reducing K-ATP channel density and current in the plasma membrane.
2012
- Role of phospholipase C-epsilon in physiological phosphoinositide signaling networks,
Cellular Signaling 2012
This review concerning PLC-epsilon was a collaboration of Drs. Alan V. Smrcka, Joan Heller Brown, and George G. Holz. Summarized are current concepts regarding how Epac signals through Rap in order to control PLC-epsilon activity, thereby influencing Ca2+ handling, excitation-contraction coupling, and exocytosis in various cell types. - cAMP Sensor Epac and Gastrointestinal Function,
Physiology of the Gastrointestinal Tract, Fifth Edition 2012
Summarized in this handbook chapter are the surprisingly diverse roles Epac proteins play in gastrointestinal function. The work was a collaboration of the Holz laboratory with Dr. Xiaodong Cheng of the University of Texas Medical Branch in Galveston, TX. - Isoform-specific antagonists of exchange proteins directly activated by cAMP,
Proceedings of the National Academy of Sciences 2012
A major breakthrough for the field of signal transduction research was the discovery by Dr. Xiaodong Cheng of small molecule compounds (ESI-05, ESI-07) that specifically inhibit Epac2 while leaving Epac1 and PKA unaffected. The specificity of ESI-05 and ESI-07 was validated in FRET-based assays of Epac or PKA activation, as performed in the Holz laboratory by Drs. Oleg G. Chepurny and Colin A. Leech.
2011
- Phospholipase C-epsilon links Epac2 activation to the potentiation of glucose-stimulated insulin secretion from mouse islets of Langerhans,
Islets 2011
This report provided the first evidence that a novel Epac2 and Rap1 -regulated PLC-epsilon mediates the action of cAMP to potentiate glucose-stimulated insulin secretion from mouse islets. Consistent with this concept, the insulin secretagogue action of an Epac activator (8-pCPT-2'-O-Me-cAMP-AM) was found to be diminished in islets of Epac2 and PLC-epsilon KO mice. The study was a collaboration of the Holz laboratory with Dr. Youming Lu who provided the Epac2 KO mice, and Dr. Alan V. Smrcka who provided the PLC-epsilon KO mice. - Molecular physiology of glucagon-like peptide-1 insulin secretagogue action in pancreatic beta cells,
Progress in Biophysics and Molecular Biology 2011
This review provided an update concerning the molecular basis for incretin hormone action, as it pertains to insulin secretion under the control of GLP-1. New findings reported in this review included the discovery of Dr. Igor Dzhura that an Epac activator (8-pCPT-2 '-O-Me-cAMP-AM) initiated electrical "bursting" activity in mouse islets. This bursting activity was comprised of action potentials, and it occurred in synchrony with oscillations of cytosolic [Ca2+] that are known to "trigger" pulsatile insulin secretion.
2010
- PKA-dependent potentiation of glucose-stimulated insulin secretion by Epac activator 8-pCPT-2'-O-Me-cAMP-AM in human islets of Langerhans,
American Journal of Physiology 2010
This paper established the efficacy of Epac activator 8-pCPT-2 '-O-Me-cAMP-AM as a stimulator of insulin secretion from human pancreatic islets. Surprisingly, protein kinase A (PKA) activity was found to be permissive in order for the Epac activator to exert its effect. Based on this finding, our view is that Epac participates in beta-cell stimulus-secretion coupling at an "early" step upstream of PKA-dependent secretory granule exocytosis. For example, our studies demonstrate that Epac facilitates glucose-dependent K-ATP channel closure, Ca2+ influx, and Ca2+ mobilization. - Facilitation of beta-cell K-ATP channel sulfonylurea sensitivity by a cAMP analog selective for the cAMP-regulated guanine nucleotide exchange factor Epac,
Islets 2010
Clinical studies demonstrate that there is an increased risk of hypoglycemia in patients administered a sulfonylurea and a GLP-1 receptor agonist. Our 2010 paper published in Islets provided evidence that this clinical observation can be explained by the synergistic interaction of sulfonylureas and GLP-1 receptor agonists to promote beta-cell K-ATP channel closure. - Epac2-dependent mobilization of intracellular Ca2+ by glucagon-like peptide-1 receptor agonist exendin-4 is disrupted in beta cells of phospholipase C-epsilon knockout mice,
Journal of Physiology 2010
Epac2 is an activator of the small GTPase Rap1, and Rap1 is know to participate in the stimulation of insulin secretion by cAMP-elevating agents such as GLP-1. This 2010 paper provided the first evidence that the Ca2+ dependent exocytosis of insulin might be stimulated as a consequence of the Epac2 and Rap1 mediated activation of a novel phosphoinositide-specific phospholipase C-epsilon. The study was a collaboration of the Holz laboratory with the laboratory of Dr. Alan V. Smrcka of the University of Rochester School of Medicine. - Epac2-dependent Rap1 activation and the control of islet insulin secretion by glucagon-like peptide-1,
Vitamins and Hormones 2010
This review summarized current concepts regarding the relative contributions of Epac2 and PKA to the control of islet insulin secretion by GLP-1 receptor agonists. An overview was provided concerning which steps of beta-cell stimulus-secretion coupling are under the control of Epac2 and/or PKA.
2009
- Enhanced Rap1 activation and insulin secretagogue properties of an acetoxymethyl ester of an Epac-selective cyclic AMP analog in rat INS-1 cells: studies with 8-pCPT-2'-O-Me-cAMP-AM,
The Journal of Biological Chemistry 2009
Soon after the Holz laboratory moved from NYU School of Medicine to SUNY Upstate Medical University, we collaborated with the BIOLOG Life Science Institute in order to demonstrate the potent insulin secretagogue action of a novel AM-ester of an Epac-selective cAMP analog (ESCA). Such AM-esters of ESCAs are powerful new tools with which to study Epac signal transduction since these compounds have especially high membrane permeability. - Glucose-dependent potentiation of mouse islet insulin secretion by Epac activator 8-pCPT-2'-O-Me-cAMP-AM,
Islets 2009
Working with Dr. Grant G. Kelley of SUNY Upstate, the Holz laboratory was the first to document that the AM-ester of 8-pCPT-2 '-O-Me-cAMP exerted a powerful stimulatory action in mouse islets to potentiate first and second phase glucose-stimulated insulin secretion (GSIS). These findings resolved a long-standing discrepancy in the literature in which the non-AM ester of this Epac activator was reported to either stimulate, or not stimulate, islet insulin secretion. - Glucagon-like peptide-1 induced signaling and insulin secretion do not drive fuel and energy metabolism in primary rodent pancreatic beta-cells,
PLoS One 2009
This collaborative study of the Holz (SUNY), Prentki (University of Montreal), and Heart (MBL) labs re-examined whether GLP-1 renders beta-cells "glucose competent" by upregulating oxidative glucose metabolism in the beta cells. Surprisingly, and in contrast to findings of Tsuboi et al. 2003 for insulin-secreting MIN6 cells, no such action of GLP-1 was measurable in isolated human or mouse islets.
2008
- Role of the cAMP sensor Epac as a determinant of K-ATP channel ATP-sensitivity in human pancreatic beta cells and rat INS-1 cells,
Journal of Physiology 2008
This paper was the first to demonstrate that an Epac-selective cAMP analog has the capacity to render beta-cell K-ATP channels more sensitive to the inhibitory action of ATP. This finding provides one possible explanation for how cAMP-elevating hormone GLP-1 acts as a beta-cell glucose sensitizer to enhance insulin secretion. - Cytosolic adenylate kinases regulate K-ATP channel activity in human beta-cells,
Biochemical and Biophysical Research Communications 2008
Reported in this paper are new findings concerning the role of adenylate kinases as intermediaries linking intracellular glucose metabolism to the closure of K-ATP channels in human beta cells. - Epac-selective cAMP analogs: New tools with which to evaluate the signal transduction properties of cAMP-regulated guanine nucleotide exchange factors,
Cellular Signaling 2008
This review constitutes a collaboration of the Holz lab with Dr. Frank Schwede of the BIOLOG Life Science Institute. Summarized is an account of research that led to the generation of Epac-selective cAMP analogs (ESCAs). Also summarized are the structural and pharmacological properties of these ESCAs. - Synchronizing Ca2+ and cAMP oscillations in pancreatic beta cells: a role for glucose metabolism and GLP-1 receptors?
American Journal of Physiology, Cell Physiology 2008
This commentary provides a summary of our understanding as to how beta-cell glucose metabolism and GLP-1 signal transduction interact to generate oscillations of Ca2+ and cAMP that are in-phase, and that stimulate pulsatile insulin secretion. The paper represents a collaboration of the Holz lab with Dr. Emma Heart of the Marine Biological Laboratory, Woods Hole, MA.
2007
- A novel cyclic adenosine monophosphate-responsive luciferase reporter incorporating a nonpalindromic cyclic adenosine monophosphate response element provides optimal performance for use in G protein-coupled receptor drug discovery efforts,
Journal of Biomolecular Screening 2007
This paper describes the invention of a luciferase reporter that is cAMP responsive, and that is useful for screening of cell lines that express G protein-coupled receptors. New ligands that activate these receptors can be identified, or ligands with known structures can be evaluated in order to determine their efficacies or potencies.
2006
- Cell physiology of cAMP sensor Epac, The Journal of Physiology Topical Review 2006
This Topical review highlights the emerging role of cAMP sensor Epac as a central player in multiple aspects of cell physiology. The novel pharmacological properties and physiological actions of Epac-selective cAMP analogs (ESCAs) are also updated. - Simultaneous Optical Measurements of Cytosolic Ca2+ and cAMP in Single Cells,
Science's STKE 2006
Our collaboration with the laboratory of Dr. Michael W. Roe at the University of Chicago has generated this ground-breaking technology that allows for the very first time, the simultaneous digital imaging of cAMP and calcium concentrations in single living cells. The detailed protocols described here are an extension of the prior study of the Roe, Lohse, and Holz labs (Landa et al. 2005, see below). - cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic ß cells and rat INS-1 cells,
Journal of Physiology 2006
This research paper describes a novel form of ion channel modulation in which the activity of pancreatic beta cell ATP-sensitive potassium channels is shown to be be inhibited by Epac-selective cAMP analogs. The significance of this finding is that it establishes Epac, a cAMP-regulated guanine nucleotide exchange factor (cAMP-GEF), to be a likely target for pharmacological intervention in the treatment of type 2 diabetes mellitus.
2005
- Diabetes Outfoxed by GLP-1?,
Science's STKE 2005
This perspective published originally at Science magazine's STKE web site provides our view of how GLP-1 influences pancreatic beta cell growth and differentiation. - A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic ß cells,
Journal of Physiology 2005
This research paper is the first to establish the phenomenon of Second Messenger Coincidence Detection as a key cellular signaling event underlying the ability of a GLP-1 receptor agonist (Exendin-4, also known as Byetta) to stimulate pancreatic beta cell function. - Interplay of Ca2+ and cAMP Signaling in the Insulin-secreting MIN6 ß-Cell Line,
Journal of Biological Chemistry 2005
This research paper is the first to demonstrate that a newly-developed Epac-based FRET reporter can be activated as a consequence of GLP-1 receptor stimulation in pancreatic beta cells. The significance of this finding is that it establishes the cAMP-binding domain of Epac to be sensitive to the increase of cytosolic cAMP concentration that results upon stimulation of beta cells with Exendin-4. This report is an outgrowth of collaborative studies with the laboratory of Dr. Michael Roe of the University of Chicago.
2004
- New Insights Concerning the Glucose-dependent Insulin Secretagogue Action of Glucagon-like Peptide-1 in Pancreatic ß-Cells,
Hormone and Metabolic Research 2004
This review summarizes our view of how GLP-1 and glucose metabolism interact to stimulate the secretion of insulin from pancreatic beta cells. - Epac: A New cAMP-Binding Protein in Support of Glucagon-Like Peptide-1 Receptor-Mediated Signal Transduction in the Pancreatic ß-Cell,
Diabetes 2004
This perspective highlights the potential role of cAMP-binding protein Epac as a determinant of GLP-1 signal transduction in the pancreatic beta cell.
2003
- Glucagon-Like Peptide-1 Synthetic Analogs: New Therapeutic Agents for Use in the Treatment of Diabetes Mellitus,
Current Medicinal Chemistry 2003
This review summarizes current efforts directed at the generation of GLP-1 analogs that have an extended duration of action and which are useful for treatment of type 2 diabetes mellitus. - Epac-selective cAMP Analog 8-pCPT-2'-O-Me-cAMP as a Stimulus for Ca2+-induced Ca2+ Release and Exocytosis in Pancreatic ß-Cells,
Journal of Biological Chemistry 2003
This paper describes the pharmacological properties of a newly developed cAMP analog that activates Epac and which stimulates calcium signaling and exocytosis in pancreatic beta cells. - Glucagon-like peptide-1 mobilizes intracellular Ca2+ and stimulates mitochondrial ATP synthesis in pancreatic MIN6 ß-cells,
Biochemical Journal 2003
This paper describes collaborative studies with the laboratory of Dr. G. Rutter in which stimulatory effects of GLP-1 on mitochondrial ATP production were documented. - Amplification of exocytosis by Ca2+-induced Ca2+ release in INS-1 pancreatic ß cells,
Journal of Physiology 2003
This paper was the first to demonstrate that GLP-1 receptor agonist Exendin-4 stimulates exocytosis by mobilizing an intracellular source of calcium.
2002
- Exendin-4 as a Stimulator of Rat Insulin I Gene Promoter Activity via bZIP/CRE Interactions Sensitive to Serine/Threonine Protein Kinase Inhibitor Ro 31-8220,
Endocrinology 2002
This paper describes our studies of regulatory elements in the rat insulin 1 gene promoter that mediate stimulatory actions of Exendin-4 on insulin gene expression. - Over-expression of the glucagon-like peptide-1 receptor on INS-1 cells confers autocrine stimulation of insulin gene promoter activity: a strategy for production of pancreatic ß-cell lines for use in transplantation,
Cell and Tissue Research 2002
This paper describes a strategy for the generation of insulin-secreting cell lines that overexpress GLP-1 receptors and which exhibit robust glucose-dependent insulin gene expression.
2001
- cAMP-regulated guanine nucleotide exchange factor II (Epac2) mediates Ca2+-induced Ca2+ release in INS-1 pancreatic ß-cells,
Journal of Physiology 2001
This paper was the first to establish a link between GLP-1 receptors, activation of Epac, and the mobilization of intracellular calcium.
2000
- Glucagon-Like Peptide 1 Stimulates Insulin Gene Promoter Activity by Protein Kinase A-Independent Activation of the Rat Insulin I Gene cAMP Response Element,
Diabetes 2000
This paper was the first to demonstrate that protein kinase A-independent signaling pathways mediate stimulatory actions of GLP-1 at the insulin gene promoter.
1990-1999
- cAMP-dependent Mobilization of Intracellular Ca2+ Stores by Activation of Ryanodine Receptors in Pancreatic ß-Cells,
Journal of Biological Chemistry 1999
This paper established a link between GLP-1, cAMP production, and the release of calcium from intracellular calcium stores in beta-cells. - Leptin Suppression of Insulin Secretion and Gene Expression in Human Pancreatic Islets: Implications for the Development of Adipogenic Diabetes Mellitus,
Journal of Clinical Endocrinology and Metabolism 1999
This study examined the action of Leptin - a newly described "obesity hormone" that was found to inhibit pancreatic beta cell insulin gene expression. The findings were generated at Massachusetts General Hospital through the collaboration of Dr. Holz with Dr. Jochen Seufert while working in the laboratory of Dr. Joel F. Habener. - Leptin Suppression of Insulin Secretion by the Activation of ATP-Sensitive K+ Channels in Pancreatic ß-Cells,
Diabetes 1997
This was the first published study to demonstrate that the "obesity hormone" Leptin stimulates the function of ATP-sensitive potassium channels. Leptin receptors on pancreatic beta cells were characterized, and the inhibitory action of leptin on beta cell insulin secretion was established. The findings were generated through a collaboration of Dr. Holz with Dr. Timothy Kieffer while working in the laboratory of Dr. Joel F. Habener at Massachusetts General Hospital. - Signal transduction of PACAP and GLP-1 in pancreatic beta cells,
Annals of the New York Academy of Sciences 1996
This review summarized our laboratory's findings concerning the cAMP-mediated actions of PACAP and GLP-1 to activate non-selective cation channels in pancreatic beta cells. These findings were presented by Drs. George Holz and Colin Leech at a meeting of the New York Academy of Sciences in New Orleans, LA. - Activation of a cAMP-regulated Ca2+-Sgnaling Pathway in Pancreatic ß-Cells by the Insulinotropic Hormone Glucagon-like Peptide-1,
Journal of Biological Chemistry 1995
This paper established a role for non-selective cation channels as targets of cAMP signaling in pancreatic beta cells. In addition to its inhibitory effect at ATP-sensitive potassium channels, GLP-1 promotes sodium-dependent depolarization of beta cells, thereby increasing levels of cytosolic calcium. The study was a collaboration with Dr. Colin A. Leech of Massachusetts General Hospital while working in the laboratory of Dr. Joel F. Habener. - Pituitary Adenylate Cyclase-Activating Polypeptide Induces the Voltage-Independent Activation of Inward Membrane Currents and Elevation of Intracellular Calcium in HIT-T15 Insulinoma Cells,
Endocrinology 1995
This paper describes the stimulatory action of the neuropeptide PACAP on beta cell function. PACAP is structurally-related to GLP-1, and the PACAP receptor bears resemblence to the GLP-1 receptor. The study was a collaboration with Dr. Colin A. Leech of Massachusetts General Hospital while working in the laboratory of Dr. Joel F. Habener. - Application of patch clamp methods to the study of calcium currents and calcium channels,
Methods in Cell Biology 1994
This review concerning patch clamp electrophysiology was published in Volume 40 pgs. 135-151 of Methods in Cell Biology for the issue "A Practical Guide to the Study of Calcium in Living Cells". - Voltage-Independent Calcium Channels Mediate Slow Oscillations of Cytosolic Calcium That Are Glucose Dependent in Pancreatic ß-Cells,
Endocrinology 1994
This study demonstrated that spontaneous oscillations of intracellular calcium concentration can occur in beta cells, a phenomenon not necessarily linked to membrane depolarization. The findings are of interest in view of the role of intracellular calcium stores as determinants of beta cell stimulus-secretion coupling and regulated gene expression. The study was a collaboration with Dr. Colin A. Leech of Massachusetts General Hospital while working in the laboratory of Dr. Joel F. Habener. - Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7-37),
Nature 1993
This letter to Nature was the first published study in support of the Glucose Competence Concept. Our view is that GLP-1 restores the ability of compromised beta cells to metabolize glucose and to secrete insulin. The induction of glucose competence is measurable as the synergistic interaction of GLP-1 and glucose to inhibit ATP-sensitive potassium channels in beta cells. The study was a collaboration with Dr. Willem M. Khutreiber of Massachusetts General Hospital while working in the laboratory of Dr. Joel F. Habener. - Signal transduction crosstalk in the endocrine system: pancreatic ß-cells and the glucose competence concept,
Trends In Biochemical Sciences 1992
This review concerning the Glucose Competence Concept was published in a thematic issue of Trends in Biochemical Sciences. This issue signified the emergence of Signal Transduction as a dominant theme in contemporary biology. It was also the first formal publication generated by Dr. Holz as a consequence of his collaboration with Dr. Joel F. Habener, co-discoverer of GLP-1.
1986-1989
- G Proteins Couple a-Adrenergic and GABAb Receptors to Inhibition of Peptide Secretion from Peripheral Sensory Neurons,
Journal of Neuroscience 1989
This research report is the culmination of postdoctoral studies performed by Dr. Holz while working in the laboratory of Dr. Kathleen Dunlap at Tufts University School of Medicine. The findings demonstrate that alpha-adrenergic receptors, GABA-B receptors, Pertussis Toxin-Sensitive G proteins, and Voltage-Dependent Calcium Channels constitute a "signaling module" which when activated, generates presynaptic inhibition of neuropeptide secretion from peripheral sensory neurons. - Characterization of the Electrically Evoked Release of Substance P from Dorsal Root Ganglion Neurons: Methods and Dihydropyridine Sensitivity,
Journal of Neuroscience 1988
The role of L-type and N-type Voltage-Dependent Calcium Channels as determinants of neuropeptide secretion was first established in this study examining the exocytosis of Substance P from peripheral sensory neurons. This is the first study to demonstrate that the electrically-evoked release of a neuropeptide results from depolarization-induced activation of omega-conotoxin GVIA-sensitive N-type Calcium channels. - G proteins as regulators of ion channel function,
Trends In Neuroscience 1987
This review provided the impetus for numerous studies examining the role of heterotrimeric G proteins as signaling intermediaries linking G protein-coupled receptors to the modulation of Calcium and Potassium channels in excitable cells. - Modifying channel function,
Nature 1986 News and Views
This is the News and Views article which accompanied our 1986 report in Nature concering G protein regulation of voltage-dependent calcium channels. - GTP-binding proteins mediate transmitter inhibition of voltage-dependent calcium channels,
Nature 1986
This is the paper that established a link between activation of G proteins and the inhibition of voltage-dependent calcium channels. It was the most highly cited paper in the field of Neuroscience for the year 1986 according to the ISI. Publication of this study was facilitated by the generosity of Dr. Ronald D. Sekura of the NIH who provided Dr. Holz purified preparations of Bordetella pertussis toxin, which at that time were not commercially available. - Serotonin Decreases the Duration of Action Potentials Recorded from Tetraethylammonium-Treated Bullfrog Dorsal Root Ganglion Cells,
Journal of Neuroscience 1986
This research report summarizes the Ph.D. studies of Dr. Holz performed while working in the laboratory of Dr. Edmund G. Anderson, Chairman of Pharmacology at the University of Illinois in Chicago. The role of serotonin receptors in the generation of presynaptic inhibition was investigated in electrophysiological studies of primary sensory neurons.
Lab of Drs. George G. Holz, Malek El Muayed, & Tuncay Delibasi
Dr. George G. Holz's Research Interests
Drug discovery research in the Holz laboratory at SUNY Upstate seeks to establish new pharmacological approaches to the treatment of type 2 diabetes and obesity. In this regard, our prior findings helped lead to FDA approval of the GLP-1 receptor agonists Byetta, Victoza, Ozempic and Wegovy as new blood glucose-lowering agents with appetite-suppressing properties. One focus of the laboratory now concerns synthetic hyprid peptides with GPCR activating properties, as validated in high-throughput FRET assays using cAMP and Ca2+ biosensors. Such hybrid peptides incorporating amino acid motifs within GLP-1, Glucagon, GIP and Peptide YY are likely to be of a unique medical importance in that they have the potential to exhibit novel dual or tri agonist properties with subcutaneous administration.
Contact: George G. Holz, PhD
Location: Institute for Human Performance
Phone: (315) 464-9841
Email: holzg@upstate.edu
Dr. Malek El Muayed's Research Interests
Malek El Muayed, MD, MS
Assistant Professor
Dr. Muayed's research interests include Diabetes and Insulin Resistance, Obesity and Leptin Biology, Metabolism and Metabolic Health, Islet and Stem Cell Therapy, RNA Therapeutics, and Pharmacogenetics.
Dr. Tuncay Delibasi's Research Interests
Tuncay Delibasi, MD
Assistant Professor
Dr. Delibasi's research interests include Diabetes and Insulin Resistance, Obesity and Leptin Biology, Metabolism and Metabolic Health, Islet and Stem Cell Therapy, RNA Therapeutics, and Pharmacogenetics.
We encourage you to learn more about our Clinical Trials and Laboratory Research.
If you're interested in Upstate Medical University in Syracuse, New York, our Endocrine, Diabetes & Metabolism research division or any of our Endocrine, Diabetes & Metabolism research projects, we encourage you to contact us today at (315) 464-9753. One of our dedicated research staff members will be happy to answer all and any questions you may have about our research department.
