Rat maternal diabetes impairs pancreatic β-cell function in the offspring

Abstract

It has been shown that maternal diabetes increases the risk for obesity, glucose intolerance, and Type 2 diabetes mellitus in the adult life of the offspring. Mechanisms for these effects on the offspring are not well understood, and little information is available to reveal the mechanisms. We studied the effect of maternal diabetes on ␤-cell function in the offspring of streptozotocin (STZ)-induced diabetic rat mothers (STZ-offspring). STZ-offspring did not become glucose intolerant up to 15 wk of age. At this age, however, insulin secretion was significantly impaired, as measured by in vivo and in vitro studies. Consistent with these changes, islet glucose metabolism and some important glucose metabolic enzyme activities were reduced. No significant changes were found in islet morphological analysis. These data indicate that ␤-cell function is impaired in adult STZ-offspring; these changes may contribute to the development of type 2 diabetes mellitus in adulthood. insulin secretion; islets of Langerhans; type 2 diabetes mellitus EXPERIMENTAL AND CLINICAL STUDIES have shown that the incidence of diabetes is higher in the offspring of diabetic mothers than in offspring of nondiabetic mothers or diabetic fathers (20,35,39,47). Exposure to a diabetic environment in utero is associated with a substantially higher risk of obesity, glucose intolerance, and (non-insulin-dependent) type 2 diabetes mellitus (NIDDM) in the offspring (10,16,32,39,40,44,50). Intrauterine exposure to hyperglycemia is also associated with a higher prevalence of impaired glucose tolerance in adolescence (44) and with an excess of obesity, especially during the first 20 yr of life (10,40,41,45). Systematic prevention of hyperglycemia and impaired glucose tolerance in pregnant women have significantly decreased the prevalence of diabetes mellitus in their children (12). Studies of Pima Indians provide further indication for a role of maternal diabetes in utero: NIDDM is present by age 20 -24 yr in 45.5% of the offspring of diabetic mothers but only in 8.6% and 1.4% of respective offspring of prediabetic or nondiabetic mothers (39). Also in Pima Indians, offspring born after their mothers have developed NIDDM have a 3.7-fold higher risk of developing diabetes than those born before their mother have developed diabetes (11).Animal studies suggest that an adverse influence of maternal diabetes on fetal pancreatic function (4) may contribute to development of NIDDM. Maternal diabetes alters the morphology, number, and size of offspring islets and the ability of the offspring islets to respond to the challenge of pregnancy (5). Insulin secretion has been shown to be abnormal in islets from offspring of diabetic mothers (3). Glucose metabolism is the primary regulator of ␤-cell function (33, 34). However, no studies have examined the changes produced by maternal diabetes on glucose metabolism of offspring islets. In the present study, we have examined ␤-cell insulin secretion and glucose metabolism in the offspring of streptozotocin (STZ)-diabetic mo...

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