Abstract
Summary
The dynamics of insulin secretion from pancreatic islets of the Zucker-obese rat were studied by in vitro perfusion of individual islets. Glucose and l-leucine were used as insulinogenic stimuli. Control pancreatic islets were obtained from both normal weight Zucker-thin littermates and equivalent weight Sprague-Dawley rats.
Our results demonstrate that pancreatic islets from 13-wk-old Zucker-obese rats hypersecrete insulin in the basal state and in response to both glucose and amino acid (l-leucine) stimuli. Neither pancreatic islets from control Zucker-thin littermate animals (matched with the Zucker-obese animals for age or for total body weight), nor islets from Sprague-Dawley rats of comparable age and weight demonstrate comparable hypersecretion of insulin.
These findings; i.e., hypersecretion of insulin from obese pancreatic islets, suggest that the plasma hyperinsulinism characteristic of the obese state is maintained, at least in part, by an inherent abnormality of β cell secretion. Whether this abnormality in β cell secretion results from a genetic trait in the Zucker-obese strain or is induced by the insulin resistance of the obese animal is not resolved by this study. In any case, the observed in vitro hyper-insulin secretion from these islets supports the postulation that in vivo peripheral insulin resistance characteristic of obesity may be a physiological response that protects the animal from insulin-induced hypoglycemia.
This investigation was supported by U. S. Public Health Service Grant 5 ROI HE12085, by Career Development Award 1 K04 35843, and by Grants from the KROC Foundation and from Ayerst Laboratories.
This work was done during tenure of D. S. Schade by a Public Health Service Special Post-Doctoral Fellowship HEW AM 55979-01.
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