Research Topics
Species | Franz MatschinskySummaryAffiliation: University of Pennsylvania Country: USA Publications
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Publications
Glucokinase, glucose homeostasis, and diabetes mellitusFranz M Matschinsky
University of Pennsylvania Medical School, Department of Biochemistry and Biophysics, 501 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, PA 19104, USA
Curr Diab Rep 5:171-6. 2005..There is no question that the GK molecule and related issues will continue to be a fruitful topic for future research...- The network of glucokinase-expressing cells in glucose homeostasis and the potential of glucokinase activators for diabetes therapyFranz M Matschinsky
University of Pennsylvania, Department of Biochemistry and Biophysics, 501 Stemmler Hall, Philadelphia, PA 19104, USA
Diabetes 55:1-12. 2006..Future biophysical, molecular, genetic, and pharmacological studies hold much promise to unravel the evolving complexity of the glucokinase glucose sensor system... - Glucokinase activation repairs defective bioenergetics of islets of Langerhans isolated from type 2 diabeticsNicolai M Doliba
Department of Biochemistry and Biophysics, University of Pennsylvania, 415 Curie Blvd, Philadelphia, PA 19104 6140, USA
Am J Physiol Endocrinol Metab 302:E87-E102. 2012..Our data suggest that impaired ?-cell bioenergetics resulting in greatly reduced ATP production is critical in the molecular pathogenesis of type 2 diabetes mellitus... - Regulation of pancreatic beta-cell glucokinase: from basics to therapeuticsFranz M Matschinsky
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Diabetes 51:S394-404. 2002..The therapeutic application of this basic discovery offers a new principle for drug therapy of diabetes... - Assessing the potential of glucokinase activators in diabetes therapyFranz M Matschinsky
University of Pennsylvania, School of Medicine, Department of Biochemistry and Biophysics, 612 Clinical Research Building, Philadelphia, Pennsylvania 19104, USA
Nat Rev Drug Discov 8:399-416. 2009..Here, the scientific basis and current status of this new approach to diabetes therapy are discussed... - A signaling role of glutamine in insulin secretionChanghong Li
Division of Endocrinology, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 279:13393-401. 2004.... - Foxa2 regulates multiple pathways of insulin secretionKristen A Lantz
Department of Genetics, Children s Hospital of Philadelphia, Philadelphia, PA, USA
J Clin Invest 114:512-20. 2004..Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion... - Pharmacologically regulated regeneration of functional human pancreatic isletsGary P Kobinger
Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania Health System, Philadelphia, PA 19104, USA
Mol Ther 11:105-11. 2005..This strategy has the potential to reduce the quantity of human islets required for treatment of patients with Type I diabetes... - Exendin-(9-39) corrects fasting hypoglycemia in SUR-1-/- mice by lowering cAMP in pancreatic beta-cells and inhibiting insulin secretionDiva D De Leon
Division of Endocrinology, Department of Pediatrics, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 283:25786-93. 2008..Our findings indicate that exendin-(9-39) normalizes fasting hypoglycemia in SUR-1(-/-) mice via a direct effect on insulin secretion, thereby raising exendin-(9-39) as a potential therapeutic agent for K(ATP) hyperinsulinism... - The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretionRana K Gupta
Department of Genetics, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
J Clin Invest 115:1006-15. 2005..Our data provide genetic evidence that HNF-4alpha is required in the pancreatic beta cell for regulation of the pathway of insulin secretion dependent on the ATP-dependent potassium channel... - Effects of a GTP-insensitive mutation of glutamate dehydrogenase on insulin secretion in transgenic miceChanghong Li
Division of Endocrinology, The Children's Hospital of Philadelphia and Diabetes Center, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 281:15064-72. 2006..This study suggests that GDH functions predominantly in the direction of glutamate oxidation rather than glutamate synthesis in mouse islets and that this flux is tightly controlled by glucose... - Distinguishing features of leucine and alpha-ketoisocaproate sensing in pancreatic beta-cellsZhiyong Gao
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine and The Children's Hospital, Philadelphia, Pennsylvania 19104, USA
Endocrinology 144:1949-57. 2003..In conclusion, leucine and KIC stimulated beta-cells via distinct mechanisms. Glutamate dehydrogenase is the sensor of leucine, whereas transamination plays an important role in KIC stimulation of pancreatic beta-cells... - Regulation of leucine-stimulated insulin secretion and glutamine metabolism in isolated rat isletsChanghong Li
Division of Endocrinology, Children's Hospital of Philadelphia, Pennsylvania 19104, USA
J Biol Chem 278:2853-8. 2003..These mechanisms provide an explanation for hypoglycemia caused by mutations of GDH in children... - Insulin independence following isolated islet transplantation and single islet infusionsJames F Markmann
Department of Surgery, University of Pennsylvania Health System, Hospital of the University of Pennsylvania, 4th Floor Silverstein, 3400 Spruce Street, Philadelphia, PA 19104, USA
Ann Surg 237:741-9; discussion 749-50. 2003..To restore islet function in patients whose labile diabetes subjected them to frequent dangerous episodes of hypoglycemic unawareness, and to determine whether multiple transplants are always required to achieve insulin independence... - The use of non-heart-beating donors for isolated pancreatic islet transplantationJames F Markmann
Department of Surgery, University of Pennsylvania Health System, Philadelphia 19104, USA
Transplantation 75:1423-9. 2003..These results indicate that NHBDs may provide an as yet untapped source of pancreatic tissue for preparation of isolated islets for clinical transplantation... - Analysis of gene expression in pancreatic islets from diet-induced obese miceYumi Imai
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Physiol Genomics 36:43-51. 2008..Functional analyses of differentially regulated genes hold promise for elucidating factors linking obesity to alterations in islet function... - Cholinergic regulation of fuel-induced hormone secretion and respiration of SUR1-/- mouse isletsNicolai M Doliba
Dept of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Am J Physiol Endocrinol Metab 291:E525-35. 2006.... - Foxa1-deficient mice exhibit impaired insulin secretion due to uncoupled oxidative phosphorylationMarko Z Vatamaniuk
Department of Genetics and Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, 415 Curie Blvd, Philadelphia, PA 19104 6145, USA
Diabetes 55:2730-6. 2006..Chromatin immunoprecipitation assays indicate that UCP2 is a direct transcriptional target of Foxa1 in vivo. Thus, we have identified a novel function for Foxa1 in the regulation of oxidative phosphorylation in pancreatic beta-cells... - Metabolic and ionic coupling factors in amino acid-stimulated insulin release in pancreatic beta-HC9 cellsNicolai M Doliba
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, PA, USA
Am J Physiol Endocrinol Metab 292:E1507-19. 2007.... - Elimination of KATP channels in mouse islets results in elevated [U-13C]glucose metabolism, glutaminolysis, and pyruvate cycling but a decreased gamma-aminobutyric acid shuntChanghong Li
Division of Endocrinology, The Children s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 283:17238-49. 2008.... - Palmitic acid acutely inhibits acetylcholine- but not GLP-1-stimulated insulin secretion in mouse pancreatic isletsNicolai M Doliba
Department of Biochemistry and Biophysics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, 19104 6140, USA
Am J Physiol Endocrinol Metab 299:E475-85. 2010..We speculate that acute emptying of the ER calcium by PA results in decreased glucose stimulation of respiration and acetylcholine potentiation of insulin secretion... - Mechanism of hyperinsulinism in short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency involves activation of glutamate dehydrogenaseChanghong Li
Division of Endocrinology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 285:31806-18. 2010..These studies indicate that SCHAD deficiency causes hyperinsulinism by activation of GDH via loss of inhibitory regulation of GDH by SCHAD... - Insulin secretion is increased in pancreatic islets of neuropeptide Y-deficient miceYumi Imai
Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Endocrinology 148:5716-23. 2007.... - Restitution of defective glucose-stimulated insulin release of sulfonylurea type 1 receptor knockout mice by acetylcholineNicolai M Doliba
Diabetes Research Center, Department of Biochemistry and Biophysics, Univ of Pennsylvania, Philadelphia, PA 19104 6015, USA
Am J Physiol Endocrinol Metab 286:E834-43. 2004..Priming by the combination of high [Ca2+]i, ACh, and GLP-1 restores the defective glucose responsiveness, precluding the development of diabetes but not effectively enough to cause hyperinsulinemic hypoglycemia... - Differential effects of glucose and glyburide on energetics and Na+ levels of betaHC9 cells: nuclear magnetic resonance spectroscopy and respirometry studiesNicolai M Doliba
Diabetes Research Center and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
Diabetes 52:394-402. 2003.... - Rapamycin has a deleterious effect on MIN-6 cells and rat and human isletsEwan Bell
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4399, USA
Diabetes 52:2731-9. 2003.... - A glucose sensor role for glucokinase in anterior pituitary cellsDorothy Zelent
University of Pennsylvania School of Medicine, BiochemistryBiophysics, 501 Stemmler Hall, 36th and Hamilton Walk, Philadelphia, PA 19104, USA
Diabetes 55:1923-9. 2006.... - Extremes of clinical and enzymatic phenotypes in children with hyperinsulinism caused by glucokinase activating mutationsSamir Sayed
Clinical Translational Research Center, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
Diabetes 58:1419-27. 2009..We report three children with de novo glucokinase hyperinsulinism mutations who displayed a spectrum of clinical phenotypes corresponding to marked differences in enzyme kinetics... - Glutaminolysis and insulin secretion: from bedside to bench and backAndrea Kelly
Department of Pediatrics, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Diabetes 51:S421-6. 2002..These findings provide a foundation for defining pathways of basal secretion and AASIS, augmenting our understanding of beta-cell function... - Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivoCatherine S Lee
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6145, USA
Diabetes 51:2546-51. 2002..These data represent the first in vivo demonstration that Foxa2 acts upstream of Pdx1 in the differentiated beta-cell... - Transduction of human islets with pseudotyped lentiviral vectorsGary P Kobinger
Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania Health System, Philadelphia, PA 19104, USA
Hum Gene Ther 15:211-9. 2004..Overall, our study describes an improved methodology for achieving safe and efficient gene transfer into cells of human islets... - Foxa2 controls vesicle docking and insulin secretion in mature Beta cellsNan Gao
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA
Cell Metab 6:267-79. 2007..We conclude that Foxa2 is required for both fetal pancreas development and the function of mature beta cells... - Functional genomics of the beta-cell: short-chain 3-hydroxyacyl-coenzyme A dehydrogenase regulates insulin secretion independent of K+ currentsOlga T Hardy
Department of Genetics, University of Pennsylvania School of Medicine, 415 Curie Boulevard, 560 Clinical Research Building, Philadelphia, Pennsylvania 19104, USA
Mol Endocrinol 21:765-73. 2007..Our results suggest a molecular explanation for the hyperinsulinemia hypoglycemic seen in patients with SCHAD deficiency... - Structural and functional abnormalities in the islets isolated from type 2 diabetic subjectsShaoping Deng
Department of Surgery, Harrison Department of Surgical Research, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
Diabetes 53:624-32. 2004..These results provide direct evidence for abnormalities in the islets of type 2 diabetic patients that may contribute to the pathogenesis of the disease... - Sugar binding to recombinant wild-type and mutant glucokinase monitored by kinetic measurement and tryptophan fluorescenceBogumil Zelent
Department of Biochemistry and Biophysics and Diabetes Research Center, University of Pennsylvania, Philadelphia, PA 19104, USA
Biochem J 413:269-80. 2008.... - The second activating glucokinase mutation (A456V): implications for glucose homeostasis and diabetes therapyHenrik B T Christesen
Department of Pediatrics, Odense University Hospital, Odense, Denmark
Diabetes 51:1240-6. 2002..Mathematical modeling predicted a markedly lowered GSIR threshold of 1.5 mmol/l. The theoretical and practical implications are manifold and significant... - Allosteric activators of glucokinase: potential role in diabetes therapyJoseph Grimsby
Department of Metabolic Diseases, Hoffmann-La Roche Inc, Nutley, NJ 07110, USA
Science 301:370-3. 2003..These findings may lead to the development of new drug therapies for diabetes... - Protein kinase A translocation and insulin secretion in pancreatic beta-cells: studies with adenylate cyclase toxin from Bordetella pertussisZhiyong Gao
Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia and University of Pennsylvania School of Medicine, 5135 Main Building, 34th Street and Civic Center Blvd, Philadelphia, PA 19104 4399, U S A
Biochem J 368:397-404. 2002..In conclusion, glucose and GLP-1 amplify insulin secretion via cAMP production and PKAbeta activation... - Insights into the structure and regulation of glucokinase from a novel mutation (V62M), which causes maturity-onset diabetes of the youngAnna L Gloyn
Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, United Kingdom
J Biol Chem 280:14105-13. 2005..Elucidating such mechanisms leads to a deeper understanding of the GCK glucose sensor and the biochemistry of beta-cells and hepatocytes... - Glucokinase thermolability and hepatic regulatory protein binding are essential factors for predicting the blood glucose phenotype of missense mutationsMaria F Pino
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
J Biol Chem 282:13906-16. 2007.... - Permanent neonatal diabetes caused by glucokinase deficiency: inborn error of the glucose-insulin signaling pathwayPål R Njølstad
Department of Pediatrics, Haukeland University Hospital, University of Bergen, Norway
Diabetes 52:2854-60. 2003..Autosomal recessive inheritance and enzyme deficiency are features typical for an inborn error of metabolism, which occurred in the glucose-insulin signaling pathway in these subjects... - Green tea polyphenols modulate insulin secretion by inhibiting glutamate dehydrogenaseChanghong Li
Donald Danforth Plant Science Center, 975 Warson Road, St. Louis, MO 63132, USA
J Biol Chem 281:10214-21. 2006..These results demonstrate that EGCG, much like the activator of GDH (BCH), can facilitate dissecting the complex regulation of insulin secretion by pharmacologically modulating the effects of GDH... - Insights into the biochemical and genetic basis of glucokinase activation from naturally occurring hypoglycemia mutationsAnna L Gloyn
Department of Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, UK
Diabetes 52:2433-40. 2003..In vitro studies confirm the validity of structural and functional models of GCK and the putative allosteric activator site, which is a potential drug target for the treatment of type 2 diabetes... - Immunohistochemical evidence for the presence of glucokinase in the gonadotropes and thyrotropes of the anterior pituitary gland of rat and monkeyRobert L Sorenson
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, USA
J Histochem Cytochem 55:555-66. 2007.... - Cell biology assessment of glucokinase mutations V62M and G72R in pancreatic beta-cells: evidence for cellular instability of catalytic activityCatherine Arden
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
Diabetes 56:1773-82. 2007..These results suggest that cellular loss of GK catalytic activity rather than impaired translation or enhanced protein degradation may account for the hyperglycemia in subjects with V62M and G72R mutations...
Research Grants
- METABOLISM OF ISLETS OF LANGERHANS AND HORMONE RELEASEFranz M Matschinsky; Fiscal Year: 2010..3) Explore the biochemistry and physiological significance of glucokinase in gonadotropes and thyrotropes of the pituitary gland to help understand the extra-pancreatic and extra-hepatic role of the enzyme. ..
- METABOLISM OF ISLETS OF LANGERHANS AND HORMONE RELEASEFranz Matschinsky; Fiscal Year: 2007..3) Explore the biochemistry and physiological significance of glucokinase in gonadotropes and thyrotropes of the pituitary gland to help understand the extra-pancreatic and extra-hepatic role of the enzyme. ..
- METABOLISM OF ISLETS OF LANGERHANS AND HORMONE RELEASEFranz Matschinsky; Fiscal Year: 2006....
- METABOLISM OF ISLETS OF LANGERHANS AND HORMONE RELEASEFranz Matschinsky; Fiscal Year: 2002....