Research Topics
Genomes and Genes | George HolzSummaryAffiliation: 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
Research Grants
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Detail Information
Publications
Role of phospholipase Cε in physiological phosphoinositide signaling networksAlan 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...- Simultaneous optical measurements of cytosolic Ca2+ and cAMP in single cellsMark 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... - Cell physiology of cAMP sensor EpacGeorge 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... - cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cellsGuoxin Kang
Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY, USA
J Physiol 573:595-609. 2006.... - Interplay of Ca2+ and cAMP signaling in the insulin-secreting MIN6 beta-cell lineLuis R Landa
Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 280:31294-302. 2005.... - A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic beta cellsGuoxin 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... - 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... - New insights concerning the glucose-dependent insulin secretagogue action of glucagon-like peptide-1 in pancreatic beta-cellsG 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... - Epac: A new cAMP-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic beta-cellGeorge 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... - Glucagon-like peptide-1 synthetic analogs: new therapeutic agents for use in the treatment of diabetes mellitusGeorge 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... - In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusionAndreea 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... - Amplification of exocytosis by Ca2+-induced Ca2+ release in INS-1 pancreatic beta cellsGuoxin 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... - Epac-selective cAMP analog 8-pCPT-2'-O-Me-cAMP as a stimulus for Ca2+-induced Ca2+ release and exocytosis in pancreatic beta-cellsGuoxin Kang
Department of Physiology and Neuroscience, New York University School of Medicine, New York 10016, USA
J Biol Chem 278:8279-85. 2003.... - Glucagon-like peptide-1 mobilizes intracellular Ca2+ and stimulates mitochondrial ATP synthesis in pancreatic MIN6 beta-cellsTakashi 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... - 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 effortsOleg 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.... - Epac-selective cAMP analogs: new tools with which to evaluate the signal transduction properties of cAMP-regulated guanine nucleotide exchange factorsGeorge 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... - Molecular physiology of glucagon-like peptide-1 insulin secretagogue action in pancreatic β cellsColin 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... - Phospholipase C-ε links Epac2 activation to the potentiation of glucose-stimulated insulin secretion from mouse islets of LangerhansIgor Dzhura
Department of Medicine, State University of New York, Upstate Medical University, Syracuse, NY, USA
Islets 3:121-8. 2011.... 
Glucose-dependent potentiation of mouse islet insulin secretion by Epac activator 8-pCPT-2'-O-Me-cAMP-AMGrant 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...- Epac2-dependent rap1 activation and the control of islet insulin secretion by glucagon-like peptide-1Colin 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... - 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 miceIgor Dzhura
Department of Medicine, State University of New York Upstate Medical University, Syracuse, NY, USA
J Physiol 588:4871-89. 2010.... - Facilitation of ß-cell K(ATP) channel sulfonylurea sensitivity by a cAMP analog selective for the cAMP-regulated guanine nucleotide exchange factor EpacColin A Leech
Department of Medicine, State University of New York, Syracuse, USA
Islets 2:72-81. 2010.... - PKA-dependent potentiation of glucose-stimulated insulin secretion by Epac activator 8-pCPT-2'-O-Me-cAMP-AM in human islets of LangerhansOleg 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... - Glucagon-like peptide-1 induced signaling and insulin secretion do not drive fuel and energy metabolism in primary rodent pancreatic beta-cellsMarie 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.... - 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-AMOleg 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... - Cytosolic adenylate kinases regulate K-ATP channel activity in human beta-cellsVioleta 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... - Role of the cAMP sensor Epac as a determinant of KATP channel ATP sensitivity in human pancreatic beta-cells and rat INS-1 cellsGuoxin 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... - 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 - Exendin-4 as a stimulator of rat insulin I gene promoter activity via bZIP/CRE interactions sensitive to serine/threonine protein kinase inhibitor Ro 31-8220Oleg 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... - Syntaxin-3 and syntaxin-1A inhibit L-type calcium channel activity, insulin biosynthesis and exocytosis in beta-cell linesY Kang
Department of Medicine, University of Toronto, Ontario, Canada
Diabetologia 45:231-41. 2002..CONCLUSIONS/INTERPRETATION: These results demonstrate that Syn-1A and -3 possess strong inhibitory actions on both insulin exocytosis and insulin biosynthesis whereas Syn-2 and -4 do not inhibit the insulin secretory process... 
Tegument galactosylceramides of the cestode Spirometra mansonoidesB 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...- Fatty acid and sterol metabolism of cultured Trichomonas vaginalis and Tritrichomonas foetusD 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).. - Characterization of glycosyl phosphatidylinositol lipids of parasitic protozoans: Leishmania mexicana mexicana promastigotes, Trypanosoma cruzi Peru epimastigotes and Tritrichomonas foetusB 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... - Phospholipid metabolism of cultured Trichomonas vaginalis and Tritrichomonas foetusD H Beach
Department of Microbiology and Immunology, SUNY Health Science Center, Syracuse
Mol Biochem Parasitol 44:97-108. 1991.... - 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 transplantationOleg 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.... - cAMP-regulated guanine nucleotide exchange factor II (Epac2) mediates Ca2+-induced Ca2+ release in INS-1 pancreatic beta-cellsG 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... - Insulinotropic toxins as molecular probes for analysis of glucagon-likepeptide-1 receptor-mediated signal transduction in pancreatic beta-cellsG 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.... - 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+... - Black widow spider alpha-latrotoxin: a presynaptic neurotoxin that shares structural homology with the glucagon-like peptide-1 family of insulin secretagogic hormonesG 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... - Pertussis toxin-sensitive GTP-binding proteins characterized in synaptosomal fractions of embryonic avian cerebral cortexG 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... - Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cellsT J Kieffer
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
Diabetes 46:1087-93. 1997....
Research Grants
- Insulinotropin: A Modulator Of B-Cell Glucose SignalingGEORGE 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. ..
- Insulinotropin: A Modulator Of B-Cell Glucose SignalingGEORGE 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. ..
- MOLECULAR BASIS OF ANTIDIABETOGENIC HORMONE ACTIONGeorge 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. ..