George Holz

Summary

Affiliation: SUNY Upstate Medical University
Location: Syracuse, USA
URL: http://www.linkedin.com/pub/george-g-holz/b/88b/a18
Summary:
Professor of Medicine and Pharmacology

Publications

  1. pmc Role of phospholipase Cε in physiological phosphoinositide signaling networks
    Alan V Smrcka
    Department of Pharmacology and Physiology, University of Rochester School of Medicine, 601 Elmwood Ave, Rochester, NY 14642, USA
    Cell Signal 24:1333-43. 2012
  2. pmc Simultaneous optical measurements of cytosolic Ca2+ and cAMP in single cells
    Mark C Harbeck
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    Sci STKE 2006:pl6. 2006
  3. pmc Cell physiology of cAMP sensor Epac
    George G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    J Physiol 577:5-15. 2006
  4. pmc cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells
    Guoxin Kang
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY, USA
    J Physiol 573:595-609. 2006
  5. pmc Interplay of Ca2+ and cAMP signaling in the insulin-secreting MIN6 beta-cell line
    Luis R Landa
    Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 280:31294-302. 2005
  6. pmc A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic beta cells
    Guoxin Kang
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    J Physiol 566:173-88. 2005
  7. pmc Diabetes outfoxed by GLP-1?
    George G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    Sci STKE 2005:pe2. 2005
  8. pmc New insights concerning the glucose-dependent insulin secretagogue action of glucagon-like peptide-1 in pancreatic beta-cells
    G G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, NY 10016, USA
    Horm Metab Res 36:787-94. 2004
  9. pmc Epac: A new cAMP-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic beta-cell
    George G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA
    Diabetes 53:5-13. 2004
  10. pmc Glucagon-like peptide-1 synthetic analogs: new therapeutic agents for use in the treatment of diabetes mellitus
    George G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, 10016, USA
    Curr Med Chem 10:2471-83. 2003

Collaborators

Detail Information

Publications61

  1. pmc Role of phospholipase Cε in physiological phosphoinositide signaling networks
    Alan V Smrcka
    Department of Pharmacology and Physiology, University of Rochester School of Medicine, 601 Elmwood Ave, Rochester, NY 14642, USA
    Cell Signal 24:1333-43. 2012
    ..These studies together reveal a surprisingly wide range of unexpected functions for PLCε in cellular signaling, physiology and disease...
  2. pmc Simultaneous optical measurements of cytosolic Ca2+ and cAMP in single cells
    Mark C Harbeck
    Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
    Sci STKE 2006:pl6. 2006
    ..This real-time imaging method allows investigation of the dynamic organization and integration of multiple levels of signal processing in single living cells...
  3. pmc Cell physiology of cAMP sensor Epac
    George G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    J Physiol 577:5-15. 2006
    ..Emphasized is the emerging role of Epac in the cAMP-dependent regulation of ion channel function, intracellular Ca(2+) signalling, ion transporter activity and exocytosis...
  4. pmc cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells
    Guoxin Kang
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY, USA
    J Physiol 573:595-609. 2006
    ....
  5. pmc Interplay of Ca2+ and cAMP signaling in the insulin-secreting MIN6 beta-cell line
    Luis R Landa
    Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 280:31294-302. 2005
    ....
  6. pmc A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic beta cells
    Guoxin Kang
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    J Physiol 566:173-88. 2005
    ..We propose that second messenger coincidence detection of this type may explain how GLP-1 interacts with beta cell glucose metabolism to stimulate insulin secretion...
  7. pmc Diabetes outfoxed by GLP-1?
    George G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    Sci STKE 2005:pe2. 2005
    ..This STKE Perspective summarizes signaling properties of GLP-1 that may explain its ability to increase beta-cell mass, to increase pancreatic insulin secretory capacity, and to lower levels of blood glucose in type 2 diabetic subjects...
  8. pmc New insights concerning the glucose-dependent insulin secretagogue action of glucagon-like peptide-1 in pancreatic beta-cells
    G G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, NY 10016, USA
    Horm Metab Res 36:787-94. 2004
    ..This new "feed-forward" hypothesis of beta-cell stimulus-secretion coupling may provide a mechanistic explanation as to how GLP-1 exerts a beneficial blood glucose-lowering effect in type 2 diabetic subjects...
  9. pmc Epac: A new cAMP-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic beta-cell
    George G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA
    Diabetes 53:5-13. 2004
    ..This article summarizes new findings concerning GLP-1 receptor-mediated signal transduction and seeks to define the relative importance of Epac and PKA to beta-cell stimulus-secretion coupling...
  10. pmc Glucagon-like peptide-1 synthetic analogs: new therapeutic agents for use in the treatment of diabetes mellitus
    George G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, 10016, USA
    Curr Med Chem 10:2471-83. 2003
    ..The usefulness of synthetic GLP-1 analogs as blood glucose-lowering agents is discussed, and the applicability of GLP-1 as a therapeutic agent for treatment of type 2 diabetes is highlighted...
  11. pmc In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion
    Andreea Ianus
    Department of Pathology, New York University School of Medicine, New York, New York 10016, USA
    J Clin Invest 111:843-50. 2003
    ..The results generated with the CRE-LoxP system also suggest that in vivo cell fusion is an unlikely explanation for the "transdifferentiation" of bone marrow-derived cells into differentiated cell phenotypes...
  12. pmc Amplification of exocytosis by Ca2+-induced Ca2+ release in INS-1 pancreatic beta cells
    Guoxin Kang
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    J Physiol 546:175-89. 2003
    ..The transition from NS-type to S-type exocytosis may represent an amplification mechanism for Ca(2+)-dependent exocytosis...
  13. pmc Epac-selective cAMP analog 8-pCPT-2'-O-Me-cAMP as a stimulus for Ca2+-induced Ca2+ release and exocytosis in pancreatic beta-cells
    Guoxin Kang
    Department of Physiology and Neuroscience, New York University School of Medicine, New York 10016, USA
    J Biol Chem 278:8279-85. 2003
    ....
  14. pmc Glucagon-like peptide-1 mobilizes intracellular Ca2+ and stimulates mitochondrial ATP synthesis in pancreatic MIN6 beta-cells
    Takashi Tsuboi
    Henry Wellcome Laboratories for Integrated Cell Signalling, Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, U K
    Biochem J 369:287-99. 2003
    ..Taken together, these results demonstrate that GLP-1 potentiates glucose-stimulated insulin release in part via the mobilization of intracellular Ca(2+), and the stimulation of mitochondrial ATP synthesis...
  15. pmc 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
    Oleg G Chepurny
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York, USA
    J Biomol Screen 12:740-6. 2007
    ....
  16. pmc Epac-selective cAMP analogs: new tools with which to evaluate the signal transduction properties of cAMP-regulated guanine nucleotide exchange factors
    George G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY, USA
    Cell Signal 20:10-20. 2008
    ..Also emphasized is the usefulness of ESCAs as new tools with which to assess the role of Epac as a determinant of intracellular Ca2+ signalling, ion channel function, neurotransmitter release, and hormone secretion...
  17. pmc Molecular physiology of glucagon-like peptide-1 insulin secretagogue action in pancreatic β cells
    Colin A Leech
    Department of Medicine, State University of New York Upstate Medical University, Syracuse, NY, USA
    Prog Biophys Mol Biol 107:236-47. 2011
    ..We also discuss new evidence that provides a conceptual framework with which to understand why GLP-1R agonists are less likely to induce hypoglycemia when they are administered for the treatment of T2DM...
  18. pmc Phospholipase C-ε links Epac2 activation to the potentiation of glucose-stimulated insulin secretion from mouse islets of Langerhans
    Igor Dzhura
    Department of Medicine, State University of New York, Upstate Medical University, Syracuse, NY, USA
    Islets 3:121-8. 2011
    ....
  19. pmc Glucose-dependent potentiation of mouse islet insulin secretion by Epac activator 8-pCPT-2'-O-Me-cAMP-AM
    Grant G Kelley
    Department of Medicine, State University of New York Upstate Medical University Syracuse, NY, USA
    Islets 1:260-5. 2009
    ..Since quantitative PCR demonstrates Epac2 mRNA to be expressed at levels ca. 5.3-fold greater than that of Epac1, available evidence indicates that Epac2 does in fact mediate stimulatory actions of cAMP on mouse islet GSIS...
  20. pmc Epac2-dependent rap1 activation and the control of islet insulin secretion by glucagon-like peptide-1
    Colin A Leech
    Department of Medicine, State University of New York Upstate Medical University, Syracuse, New York, USA
    Vitam Horm 84:279-302. 2010
    ..Provided here is an overview of the Epac2 signal transduction system in β cells, with special emphasis on Rap1, a Ras-related GTPase that is an established target of Epac2...
  21. pmc Epac2-dependent mobilization of intracellular Ca²+ by glucagon-like peptide-1 receptor agonist exendin-4 is disrupted in β-cells of phospholipase C-ε knockout mice
    Igor Dzhura
    Department of Medicine, State University of New York Upstate Medical University, Syracuse, NY, USA
    J Physiol 588:4871-89. 2010
    ....
  22. pmc Facilitation of ß-cell K(ATP) channel sulfonylurea sensitivity by a cAMP analog selective for the cAMP-regulated guanine nucleotide exchange factor Epac
    Colin A Leech
    Department of Medicine, State University of New York, Syracuse, USA
    Islets 2:72-81. 2010
    ....
  23. pmc PKA-dependent potentiation of glucose-stimulated insulin secretion by Epac activator 8-pCPT-2'-O-Me-cAMP-AM in human islets of Langerhans
    Oleg G Chepurny
    Departments of Medicine, State University of New York, Syracuse, 13210, USA
    Am J Physiol Endocrinol Metab 298:E622-33. 2010
    ..This permissive action of PKA may be operative at the insulin secretory granule recruitment, priming, and/or postpriming steps of Ca(2+)-dependent exocytosis...
  24. pmc Glucagon-like peptide-1 induced signaling and insulin secretion do not drive fuel and energy metabolism in primary rodent pancreatic beta-cells
    Marie Line Peyot
    Molecular Nutrition Unit and Montreal Diabetes Research Center at the Centre de Recherche du Centre Hospitalier de l Université de Montréal and Department of Nutrition and Biochemistry, Universite de Montreal, Montreal, Quebec, Canada
    PLoS ONE 4:e6221. 2009
    ..In many cells these signals activate intermediary metabolism. However, it is not clear whether the acute amplification of GSIS by GLP-1 involves in part metabolic alterations and the production of metabolic coupling factors...
  25. pmc 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
    Oleg G Chepurny
    Departments of Medicine and Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York 13210, USA
    J Biol Chem 284:10728-36. 2009
    ..It is concluded that prior reports documenting the failure of 8-pCPT-2'-O-Me-cAMP to act in beta cells, or other cell types, need to be re-evaluated through the use of the AM-ester of this cAMP analog...
  26. pmc Cytosolic adenylate kinases regulate K-ATP channel activity in human beta-cells
    Violeta Stanojevic
    Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Biochem Biophys Res Commun 368:614-9. 2008
    ..The down-regulation of AK1 expression by hyperglycemia may contribute to the defective coupling of glucose metabolism to K-ATP channel activity in type 2 diabetes...
  27. pmc Role of the cAMP sensor Epac as a determinant of KATP channel ATP sensitivity in human pancreatic beta-cells and rat INS-1 cells
    Guoxin Kang
    Department of Physiology, New York University School of Medicine, New York, NY, USA
    J Physiol 586:1307-19. 2008
    ..On the basis of such findings it is concluded that there exists in human beta-cells and rat INS-1 cells a novel form of ion channel modulation in which the ATP sensitivity of K(ATP) channels is regulated by Epac...
  28. pmc Synchronizing Ca2+ and cAMP oscillations in pancreatic beta-cells: a role for glucose metabolism and GLP-1 receptors? Focus on "regulation of cAMP dynamics by Ca2+ and G protein-coupled receptors in the pancreatic beta-cell: a computational approach&
    George G Holz
    Am J Physiol Cell Physiol 294:C4-6. 2008
  29. pmc 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
    Oleg G Chepurny
    Department of Physiology, New York University School of Medicine, New York, New York 10016, USA
    Endocrinology 143:2303-13. 2002
    ..It is concluded that the bZIP and CRE-mediated stimulation of RIP1 by Ex-4 explains, at least in part, how this insulinotropic hormone facilitates transcriptional activity of the rat insulin I gene...
  30. pmc Syntaxin-3 and syntaxin-1A inhibit L-type calcium channel activity, insulin biosynthesis and exocytosis in beta-cell lines
    Y Kang
    Department of Medicine, University of Toronto, Ontario, Canada
    Diabetologia 45:231-41. 2002
    ..Syn-2, -3 and -4 are also present in islet beta cells but their functions are not known. Here, we investigated the role of these syntaxins in the insulin secretory process...
  31. ncbi Tegument galactosylceramides of the cestode Spirometra mansonoides
    B N Singh
    Department of Microbiology and Immunology, S U N Y Health Science Center, Syracuse 13210
    Mol Biochem Parasitol 26:99-111. 1987
    ..mansonoides may contribute to the maintenance of its normal barrier properties in the face of the varied environmental insults encountered by the cestode in its life-cycle...
  32. ncbi Fatty acid and sterol metabolism of cultured Trichomonas vaginalis and Tritrichomonas foetus
    D H Beach
    Department of Microbiology and Immunology, SUNY Health Science Center, Syracuse, NY
    Mol Biochem Parasitol 38:175-90. 1990
    ..Radiolabeled acetate, mevalonate and squalene were not incorporated into trichomonad cholesterol or cholesteryl esters. [14C]Cholesterol was incorporated unaltered, but was not esterified.(ABSTRACT TRUNCATED AT 400 WORDS)..
  33. ncbi Characterization of glycosyl phosphatidylinositol lipids of parasitic protozoans: Leishmania mexicana mexicana promastigotes, Trypanosoma cruzi Peru epimastigotes and Tritrichomonas foetus
    B N Singh
    Microbiology Immunology Department, SUNY Health Science Center, Syracuse 13210
    Indian J Biochem Biophys 27:411-5. 1990
    ..TF1 appears to be a novel class of glycophosphosphingolipid, which may be a part of a membrane anchor...
  34. ncbi Phospholipid metabolism of cultured Trichomonas vaginalis and Tritrichomonas foetus
    D H Beach
    Department of Microbiology and Immunology, SUNY Health Science Center, Syracuse
    Mol Biochem Parasitol 44:97-108. 1991
    ....
  35. pmc 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 beta-cell lines for use in transplantation
    Oleg G Chepurny
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    Cell Tissue Res 307:191-201. 2002
    ....
  36. pmc cAMP-regulated guanine nucleotide exchange factor II (Epac2) mediates Ca2+-induced Ca2+ release in INS-1 pancreatic beta-cells
    G Kang
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    J Physiol 536:375-85. 2001
    ..6. It is concluded that CICR in INS-1 cells results from GLP-1 receptor-mediated sensitization of the intracellular Ca2+ release mechanism, a signal transduction pathway independent of PKA, but which requires cAMP-GEF-II...
  37. pmc Insulinotropic toxins as molecular probes for analysis of glucagon-likepeptide-1 receptor-mediated signal transduction in pancreatic beta-cells
    G G Holz
    Department of Physiology and Neuroscience, Medical Sciences Building Room 442, New York University School of Medicine, 550 First Avenue, NY New York 10016, USA
    Biochimie 82:915-26. 2000
    ....
  38. pmc cAMP-dependent mobilization of intracellular Ca2+ stores by activation of ryanodine receptors in pancreatic beta-cells. A Ca2+ signaling system stimulated by the insulinotropic hormone glucagon-like peptide-1-(7-37)
    G G Holz
    Diabetes Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Biol Chem 274:14147-56. 1999
    ..These findings provide new support for a model of beta-cell signal transduction whereby GLP-1 promotes CICR by sensitizing intracellular Ca2+ release channels to the stimulatory influence of cytosolic Ca2+...
  39. pmc Black widow spider alpha-latrotoxin: a presynaptic neurotoxin that shares structural homology with the glucagon-like peptide-1 family of insulin secretagogic hormones
    G G Holz
    Diabetes Unit, Howard Hughes Medical Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Comp Biochem Physiol B Biochem Mol Biol 121:177-84. 1998
    ..Evidently, the toxic effects of alpha-latrotoxin and exendin-4 are explained by their ability to interact with GTP-binding protein-coupled receptors that normally mediate the actions of endogenous hormones or neuropeptides...
  40. pmc Pertussis toxin-sensitive GTP-binding proteins characterized in synaptosomal fractions of embryonic avian cerebral cortex
    G G Holz
    Diabetes Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
    Comp Biochem Physiol B Biochem Mol Biol 119:201-11. 1998
    ..These findings demonstrate multiple isoforms of M(r) 40-41 kDa Gi alpha and G(o) alpha subunits that can be identified on the basis of PTX-catalyzed ADP-ribosylation and immunoblot analysis...
  41. pmc Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells
    T J Kieffer
    Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
    Diabetes 46:1087-93. 1997
    ....
  42. pmc Stimulation of proglucagon gene expression by human GPR119 in enteroendocrine L-cell line GLUTag
    Oleg G Chepurny
    Department of Medicine, State University of New York, Upstate Medical University, Syracuse, New York 13210, USA
    Mol Endocrinol 27:1267-82. 2013
    ..Such findings are discussed within the context of ongoing controversies concerning the relative contributions of PKA and Epac2 to the control of PG gene expression. ..

Research Grants14

  1. Insulinotropin: A Modulator Of B-Cell Glucose Signaling
    GEORGE HOLZ; Fiscal Year: 2001
    ..Our goal is to elucidate the complex cellular signal transduction properties of GLP-1 that explain its effectiveness for use in treatment of diabetes mellitus. ..
  2. MOLECULAR BASIS OF ANTIDIABETOGENIC HORMONE ACTION
    George G Holz; Fiscal Year: 2010
    ..We wish to establish the molecular basis for "antidiabetogenic" properties of a new class of blood glucose-lowering agents that activate the GLP-1-R and which stimulate pancreatic insulin secretion. ..
  3. Insulinotropin: A Modulator Of B-Cell Glucose Signaling
    GEORGE HOLZ; Fiscal Year: 2007
    ..Our long term goal is to elucidate the complex signal transduction properties of GLP-1 that explain its effectiveness as a blood glucose lowering agent when used for the treatment of type 2 diabetes mellitus. ..
  4. MOLECULAR BASIS OF ANTIDIABETOGENIC HORMONE ACTION
    GEORGE HOLZ; Fiscal Year: 2009
    ..We wish to establish the molecular basis for "antidiabetogenic" properties of a new class of blood glucose-lowering agents that activate the GLP-1-R and which stimulate pancreatic insulin secretion. ..
  5. Insulinotropin: A Modulator Of B-Cell Glucose Signaling
    GEORGE HOLZ; Fiscal Year: 2007
    ..Our long term goal is to elucidate the complex signal transduction properties of GLP-1 that explain its effectiveness as a blood glucose lowering agent when used for the treatment of type 2 diabetes mellitus. ..
  6. Insulinotropin: A Modulator Of B-Cell Glucose Signaling
    GEORGE HOLZ; Fiscal Year: 2006
    ..Our long term goal is to elucidate the complex signal transduction properties of GLP-1 that explain its effectiveness as a blood glucose lowering agent when used for the treatment of type 2 diabetes mellitus. ..
  7. Insulinotropin: A Modulator Of B-Cell Glucose Signaling
    GEORGE HOLZ; Fiscal Year: 2005
    ..Our long term goal is to elucidate the complex signal transduction properties of GLP-1 that explain its effectiveness as a blood glucose lowering agent when used for the treatment of type 2 diabetes mellitus. ..
  8. Insulinotropin: A Modulator Of B-Cell Glucose Signaling
    GEORGE HOLZ; Fiscal Year: 2004
    ..Our long term goal is to elucidate the complex signal transduction properties of GLP-1 that explain its effectiveness as a blood glucose lowering agent when used for the treatment of type 2 diabetes mellitus. ..
  9. Insulinotropin: A Modulator Of B-Cell Glucose Signaling
    GEORGE HOLZ; Fiscal Year: 2003
    ..Our goal is to elucidate the complex cellular signal transduction properties of GLP-1 that explain its effectiveness for use in treatment of diabetes mellitus. ..
  10. Insulinotropin: A Modulator Of B-Cell Glucose Signaling
    GEORGE HOLZ; Fiscal Year: 2002
    ..Our goal is to elucidate the complex cellular signal transduction properties of GLP-1 that explain its effectiveness for use in treatment of diabetes mellitus. ..
  11. MOLECULAR BASIS OF ANTIDIABETOGENIC HORMONE ACTION
    George G Holz; Fiscal Year: 2010
    ..We wish to establish the molecular basis for "antidiabetogenic" properties of a new class of blood glucose-lowering agents that activate the GLP-1-R and which stimulate pancreatic insulin secretion. ..