A role for pancreatic beta-cell secretory hyperresponsiveness in catch-up growth hyperinsulinemia: Relevance to thrifty catch-up fat phenotype and risks for type 2 diabetes.
Current notions about mechanisms by which catch-up growth predisposes to later type 2 diabetes center upon those that link hyperinsulinemia with an accelerated rate of fat deposition (catch-up fat). Using a rat model of semistarvation-refeeding in which catch-up fat is driven solely by elevated metabolic efficiency associated with hyperinsulinemia, we previously reported that insulin-stimulated glucose utilization is diminished in skeletal muscle but increased in white adipose tissue. Here, we investigated the possibility that hyperinsulinemia during catch-up fat can be contributed by changes in the secretory response of pancreatic beta-cells to glucose. Using the rat model of semistarvation-refeeding showing catch-up fat and hyperinsulinemia, we compared isocalorically refed and control groups for potential differences in pancreatic morphology and in glucose-stimulated insulin secretion during in situ pancreas perfusions as well as ex vivo isolated islet perifusions. Between refed and control animals, no differences were found in islet morphology, insulin content, and the secretory responses of perifused isolated islets upon glucose stimulation. By contrast, the rates of insulin secretion from in situ perfused pancreas showed that raising glucose from 2.8 to 16.7 mmol/l produced a much more pronounced increase in insulin release in refed than in control groups (p < 0.01). These results indicate a role for islet secretory hyperresponsiveness to glucose in the thrifty mechanisms that drive catch-up fat through glucose redistribution between skeletal muscle and adipose tissue. Such beta-cell hyperresponsiveness to glucose may be a key event in the link between catch-up growth, hyperinsulinemia and risks for later type 2 diabetes.
Department of Cell Physiology and Metabolism, University of Geneva, Switzerland.
Marina
M
Casimir
Department of Medicine / Physiology, University of Fribourg, Switzerland.
Paula B
PB
de Andrade
Department of Cell Physiology and Metabolism, University of Geneva, Switzerland.
Asllan
A
Gjinovci
Department of Medicine / Physiology, University of Fribourg, Switzerland.
Jean-Pierre
JP
Montani
Department of Cell Physiology and Metabolism, University of Geneva, Switzerland.
Pierre
P
Maechler
Department of Medicine / Physiology, University of Fribourg, Switzerland.|Department of Medicine / Physiology, University of Fribourg, Rue du Musée 5, CH-1700 Fribourg, Switzerland.
Abdul G
AG
Dulloo
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