Pancreatic beta-cell-specific targeted disruption of glucokinase gene. Diabetes mellitus due to defective insulin secretion to glucose - PubMed (original) (raw)

. 1995 Dec 22;270(51):30253-6.

doi: 10.1074/jbc.270.51.30253.

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• PMID: 8530440
• DOI: 10.1074/jbc.270.51.30253

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Pancreatic beta-cell-specific targeted disruption of glucokinase gene. Diabetes mellitus due to defective insulin secretion to glucose

Y Terauchi et al. J Biol Chem. 1995.

Free article

Abstract

Mice carrying a null mutation in the glucokinase (GK) gene in pancreatic beta-cells, but not in the liver, were generated by disrupting the beta-cell-specific exon. Heterozygous mutant mice showed early-onset mild diabetes due to impaired insulin-secretory response to glucose. Homozygotes showed severe diabetes shortly after birth and died within a week. GK-deficient islets isolated from homozygotes showed defective insulin secretion in response to glucose, while they responded to other secretagogues: almost normally to arginine and to some extent to sulfonylureas. These data provide the first direct proof that GK serves as a glucose sensor molecule for insulin secretion and plays a pivotal role in glucose homeostasis. GK-deficient mice serve as an animal model of the insulin-secretory defect in human non-insulin-dependent diabetes mellitus.

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