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. 1980 Jan;65(1):207–218. doi: 10.1172/JCI109652

Adaptations of alpha2- and beta-cells of rat and mouse pancreatic islets to starvation, to refeeding after starvation, and to obesity.

F M Matschinsky, C Rujanavech, A Pagliara, W T Norfleet
PMCID: PMC371356  PMID: 6985616

Abstract

The effects of starvation and refeeding and of obesity on pancreatic alpha2- and beta-cell responses to glucose or tolbutamide were studied with the isolated rat or mouse pancreas perfused with an amino acid mixture in the presence and absence of glucose. It was observed that the physiological adaptation to a regimen of fasting and realimentation and to obesity differed greatly in the two types of endocrine cells. Whereas beta-cells of rats showed a dramatic reduction of glucose- and tolbutamide-stimulated insulin release during starvation that was reversed by refeeding, alpha2-cells preserved their response to stimulators and inhibitors during this experimental manipulation. Amino acid stimulation of glucagon release occurred equally well with the pancreas from fed and starved rats and was suppressed efficiently by glucose and tolbutamide in both nutritional states. Surprisingly, the rate of onset of glucose suppression of alpha2-cells was significantly higher in the fasted than in the fed state. This glucose hypersensitivity was apparent 2 d after after food deprivation and had disappeared again on the 2nd d of refeeding. In the pancreas from animals starved for 3 d, glucose and tolbutamide suppression of alpha2-cells took place in the absence of demonstrable changes of insulin release. In the isolated perfused pancreas taken from the hyperphagic obese hyperglycemic mouse (C57 Black/6J; ob/ob), the observed rate of insulin secretion as a result of a combined stimulus of amino acids and glucose and of glucagon release stimulated by amino acids was about four times higher than achieved by the pancreas of lean controls. However, glucose was unable to suppress the alpha2-cells in the pancreas of obese animals, in spite of the hypersection of the beta-cells, again in contrast to the alpha2-cells of controls that were readily inhibited by glucose. These data imply that the acute suppression of alpha2-cells by glucose is largely independent of a concomitant surge of extracellular insulin levels and that the adaptation of the islet organ to starvation leads to decreased glucose sensitivity of beta-cells, which contrasts with an improved glucose responsiveness of alpha2-cells. However, hyperphagia, which is assumed to be the primary abnormality in the ob/ob mouse, leads to overproduction of insulin and glucagon by the pancreas while greatly reducing the alpha2-cell sensitivity to glucose. An attempt is made to incorporate these data on starvation, refeeding, and obesity, as well as previous results with experimental diabetes, in a comprehensive picture describing a regulative principle underlying the glucose responsivness of alpha2-cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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