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Research Article Free access | 10.1172/JCI113157

Effect of chronic hyperglycemia on in vivo insulin secretion in partially pancreatectomized rats.

L Rossetti, G I Shulman, W Zawalich, and R A DeFronzo

Yale University School of Medicine, New Haven, Connecticut 06510.

Find articles by Rossetti, L. in: PubMed | Google Scholar

Yale University School of Medicine, New Haven, Connecticut 06510.

Find articles by Shulman, G. in: PubMed | Google Scholar

Yale University School of Medicine, New Haven, Connecticut 06510.

Find articles by Zawalich, W. in: PubMed | Google Scholar

Yale University School of Medicine, New Haven, Connecticut 06510.

Find articles by DeFronzo, R. in: PubMed | Google Scholar

Published October 1, 1987 - More info

Published in Volume 80, Issue 4 on October 1, 1987
J Clin Invest. 1987;80(4):1037–1044. https://doi.org/10.1172/JCI113157.
© 1987 The American Society for Clinical Investigation
Published October 1, 1987 - Version history
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Abstract

We have examined the effect of chronic (4 wk) hyperglycemia on insulin secretion in vivo in an awake, unstressed rat model. Three groups of animals were examined: control, partial (90%) pancreatectomy, and partial pancreatectomy plus phlorizin, in order to normalize plasma glucose levels. Insulin secretion in response to arginine (2 mM), hyperglycemia (+100 mg/dl), and arginine plus hyperglycemia was evaluated. In diabetic compared with control animals three specific alterations were observed: (a) a deficient insulin response, in both first and second phases, to hyperglycemia; (b) an augmented insulin response to the potentiating effect of arginine under basal glycemic conditions; and (c) an inability of hyperglycemia to augment the potentiating effect of arginine above that observed under basal glycemic conditions. Normalization of the plasma glucose profile by phlorizin treatment in diabetic rats completely corrected all three beta cell abnormalities. These results indicate that chronic hyperglycemia can lead to a defect in in vivo insulin secretion which is reversible when normoglycemia is restored.

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