Diabetes, Vol 37, Issue 2 217-222, Copyright © 1988 by American Diabetes Association

ARTICLES

Evolution of abnormal insulin secretory responses during 48-h in vivo hyperglycemia

JL Leahy and GC Weir
Research Division, Joslin Diabetes Center, Boston, MA 02215.

Recent in vitro studies have shown that insulin release caused by continuous exposure to high glucose concentration markedly falls within a few hours. We wanted to determine if a similar effect occurs in vivo with chronic intravenous infusions in normal rats. Male CD rats (200-250 g) were infused with 50% glucose at 2 ml/h for 6, 14, 24, or 48 h, whereas controls received 0.45% NaCl, and insulin responses were tested with the in vitro isolated perfused pancreas. Plasma glucose averaged 352 +/- 20 mg/dl after 4 h and 396 +/- 11 mg/dl after 24 h versus 137 +/- 5 mg/dl in controls; plasma insulin at the same times was 8.94 +/- 1.44 and 12.1 +/- 2.62 ng/ml versus 1.69 +/- 0.19 ng/ml in controls. The incremental insulin response caused by an increase in perfusate glucose from 2.8 to 16.7 mM was not significantly reduced after 24 h of glucose infusion; in contrast, paradoxical suppression was seen after 48 h. A second protocol examined glucose potentiation by giving 10 mM arginine at 2.8 and 16.7 mM glucose; a hyperresponse to arginine at the lower glucose level was present after just 14 h of infusion. Therefore, these results do not support the hypothesis that beta-cells lose their sensitivity to glucose within hours of being exposed to higher than normal glucose concentrations.
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