title: Expression of yeast hexokinase in pancreatic beta cells of transgenic mice reduces blood glucose, enhances insulin secretion, and decreases diabetes.
abstract: It has been proposed that endogenous hexokinases of the pancreatic beta cell control the rate of glucose-stimulated insulin secretion and that genetic defects that reduce beta-cell hexokinase activity may lead to diabetes. To test these hypotheses, we have produced transgenic mice that have a 2-fold increase in hexokinase activity specific to the pancreatic beta cell. This increase was sufficient to significantly augment glucose-stimulated insulin secretion of isolated pancreatic islets, increase serum insulin levels in vivo, and lower the blood glucose levels of transgenic mice by 20-50% below control levels. Elevation of hexokinase activity also significantly reduced blood glucose levels of diabetic mice. These results confirm the role of beta-cell hexokinase activity in the regulation of insulin secretion and glucose homeostasis. They also provide strong support for the proposal that reductions in beta-cell hexokinase activity can produce diabetes.
authors: Department of Pharmacology and Toxicology, University of North Dakota, Grand Forks 58203.
authors: P N
authors: PN
authors: Epstein
authors: A C
authors: AC
authors: Boschero
authors: I
authors: I
authors: Atwater
authors: X
authors: X
authors: Cai
authors: P A
authors: PA
authors: Overbeek
mesh_terms: D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015870:Gene Expression; D006593:Hexokinase / Q000502:physiology*; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D006593:Hexokinase