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, Nir Barzilai, M. Surana, Harry 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 (US)
Pages (from-to)21464-21467
Number of pages4
JournalJournal of Biological Chemistry
Volume270
Issue number37
DOIs
StatePublished - 1995

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Glucokinase
Medical problems
Animals
Animal Models
Genes
Glucose
Metabolism
Liver
Insulin
Glucose sensors
Clamping devices
Blood Glucose
Point Mutation
Mason-Type Diabetes
Hepatocytes
Fasting
Homeostasis
Phenotype

ASJC Scopus subject areas

  • Biochemistry

Cite this

Bali, D., Svetlanov, A., Lee, H. W., Fusco-DeMane, D., Leiser, M., Li, B., ... 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

Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene. / Bali, D.; Svetlanov, A.; Lee, H. W.; Fusco-DeMane, D.; Leiser, M.; Li, B.; Barzilai, Nir; Surana, M.; Hou, Harry; Fleischer, N.; DePinho, R.; Rossetti, L.; Efrat, S.

In: Journal of Biological Chemistry, Vol. 270, No. 37, 1995, p. 21464-21467.

Research output: Contribution to journalArticle

Bali, D, Svetlanov, A, Lee, HW, 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, vol. 270, no. 37, pp. 21464-21467. https://doi.org/10.1074/jbc.270.37.21464
Bali, D. ; Svetlanov, A. ; Lee, H. W. ; Fusco-DeMane, D. ; Leiser, M. ; Li, B. ; Barzilai, Nir ; Surana, M. ; Hou, Harry ; Fleischer, N. ; DePinho, R. ; Rossetti, L. ; Efrat, S. / Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene. In: Journal of Biological Chemistry. 1995 ; Vol. 270, No. 37. pp. 21464-21467.
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AU - Leiser, M.

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