Abstract P349: Decreased Complement Component C3 In Islets Is Associated With A Reduction In Pancreatic Beta Cell Area In Rat Offspring Following Chronic Placental Ischemia-induced Hypertension

Abstract

Gestational hypertension with or without low birth weight is associated with increased risk for Type 2 diabetes in offspring. Pancreatic beta cell mass is set very early in life and can influence whether an individual develops Type 2 diabetes. We previously demonstrated that postnatal day (PD)13 female offspring of rats subjected to chronic placental ischemia-induced hypertension had significantly reduced beta cell area. Previous studies in humans have noted increased circulating C3 in Type 2 diabetics, as well as an important role for intracellular complement C3 in maintaining integrity of the beta cell in the islet. Thus, we hypothesized that decreased C3 in islets is associated with reductions in beta cell area in rat offspring following placental insufficiency. The rat Reduced Uterine Perfusion Pressure (RUPP) model was used to mechanically induce placental insufficiency in the dam by placing silver clips on abdominal aorta and uterine arteries on gestation day 14 of a 21-day gestation, resulting in hypertension in the dam. Pancreatic islets and acinar were isolated by collagenase perfusion and hand picking from PD13 female offspring of RUPP and Sham dams. The concentration of C3 in serum, isolated islets and acinar was determined by ELISA. C3 was significantly increased in serum of female RUPP compared to female Sham offspring. In contrast, C3 in islets was significantly decreased in RUPP female offspring compared to Sham with no significant differences detected in acinar C3 concentrations. Thus, these data suggest that decreased C3 in islets of PD13 offspring may contribute to reduction of beta cell area and long-term susceptibility for Type 2 diabetes.