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

D. Bali, A. Svetlanov, H. W. Lee, D. Fusco-DeMane, M. Leiser, B. Li, N. Barzilai, M. Surana, H. Hou, N. Fleischer, R. DePinho, L. Rossetti, S. Efrat

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Abstract

Glucokinase catalyzes a rate-limiting step in glucose metabolism in hepatocytes and pancreatic β 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.

Original languageEnglish
Pages (from-to)21464-21467
Number of pages4
JournalJournal of Biological Chemistry
Volume270
Issue number37
DOIs
Publication statusPublished - 1995 Jan 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Bali, D., Svetlanov, A., Lee, H. W., Fusco-DeMane, D., Leiser, M., Li, B., Barzilai, N., Surana, M., Hou, H., Fleischer, N., DePinho, R., Rossetti, L., & Efrat, S. (1995). Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene. Journal of Biological Chemistry, 270(37), 21464-21467. https://doi.org/10.1074/jbc.270.37.21464