Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene.

Published

Journal Article

Glucokinase catalyzes a rate-limiting step in glucose metabolism in hepatocytes and pancreatic beta cells and is considered the "glucose sensor" for regulation of insulin secretion. Patients with maturity-onset diabetes of the young (MODY) have heterozygous point mutations in the glucokinase gene that result in reduced enzymatic activity and decreased insulin secretion. However, it remains unclear whether abnormal liver glucose metabolism contributes to the MODY disease. Here we show that disruption of the glucokinase gene results in a phenotype similar to MODY in heterozygous mice. Reduced islet glucokinase activity causes mildly elevated fasting blood glucose levels. Hyperglycemic clamp studies reveal decreased glucose tolerance and abnormal liver glucose metabolism. These findings demonstrate a key role for glucokinase in glucose homeostasis and implicate both islets and liver in the MODY disease.

Full Text

Duke Authors

Cited Authors

  • Bali, D; Svetlanov, A; Lee, HW; Fusco-DeMane, D; Leiser, M; Li, B; Barzilai, N; Surana, M; Hou, H; Fleischer, N

Published Date

  • September 15, 1995

Published In

Volume / Issue

  • 270 / 37

Start / End Page

  • 21464 - 21467

PubMed ID

  • 7665557

Pubmed Central ID

  • 7665557

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.270.37.21464

Language

  • eng

Conference Location

  • United States