Abstract

Whereas ample evidence suggests that maternal malnutrition reduces pancreatic beta-cell function, only a few studies have investigated the effect of high-fat diet during gestation and lactation on beta-cell function. Here we elucidate the effect of maternal high-fat diet on beta-cells in a mouse model. Pregnant C57BL/6J mice received 60 % high-fat diet for the duration of both gestation and lactation (HFGL), gestation only, or lactation only. Beta-cell function of the male offspring of each group at 6 weeks of age was compared with those under standard diet. Although body weight, insulin sensitivity judged by insulin tolerance test, and random glucose level were comparable among the groups, only offspring of the HFGL group showed glucose intolerance with impaired insulin secretion during intraperitoneal glucose tolerance test. A compensatory increase in pancreatic beta-cell mass was observed in the offspring of the HFGL group, and decreased glucose-stimulated insulin secretion from isolated islets was confirmed by batch-incubation and perifusion experiments. Our results demonstrated that high-fat diet consumed during gestation and lactation elicits beta-cell dysfunction in the offspring of C57BL/6J mice.

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