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J Clin Invest. 1994 Jul;94(1):399-404.

Mechanism of compensatory hyperinsulinemia in normoglycemic insulin-resistant spontaneously hypertensive rats. Augmented enzymatic activity of glucokinase in beta-cells.

Author information

1
Division of Endocrinology, Diabetes, Metabolism and Molecular Medicine, New England Medical Center, Boston, Massachusetts 02111.

Abstract

The cause of compensatory hyperinsulinemia in normoglycemic insulin-resistant states is unknown. Using spontaneously hypertensive rats (SHR), we tested the hypothesis that a lowered beta-cell set-point for glucose causes a hypersecretion of insulin at a normal glucose level. Islets isolated from normoglycemic hyperinsulinemic SHR were compared to age-matched (12 wk old) Wistar-Kyoto (WK) rats. The ED50 for glucose-induced insulin secretion was 6.6 +/- 1.0 mM glucose in SHR versus 9.6 +/- 0.5 mM glucose in WK (P < 0.02). Glucokinase enzymatic activity was increased 40% in SHR islets (P < 0.02) without any change in the glucokinase protein level by Western blot. The level of the beta-cell glucose transporter (GLUT-2) was increased 75% in SHR islets (P < 0.036). In summary, the beta-cell sensitivity for glucose was increased in these normoglycemic insulin resistant rats by an enhanced catalytic activity of glucokinase. We have identified a regulatory system for glucokinase in the beta-cell which entails variable catalytic activity of the enzyme, is modulated in response to variations in whole-body insulin sensitivity, and is not dependent on sustained changes in the plasma glucose level.

PMID:
8040280
PMCID:
PMC296322
DOI:
10.1172/JCI117335
[Indexed for MEDLINE]
Free PMC Article

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