Diabetes, Pancreatic beta cell growth and development
Pancreatic beta cells are the sole source of insulin, the hormone required for proper use of glucose. Any defect in production or utilization of insulin result in diabetes. Our lab is interested in understanding the molecular mechanisms that regulate beta cell mass and function. We use pregnancy as a physiologic model of increased insulin demand to understand how pancreatic beta cells adapt to stress. Using rodent models, we have found that intact prolactin receptor signalling is required for normal glucose homeostasis and beta cell mass expansion during pregnancy. In the absence of prolactin receptor signalling, the pregnant mice developed gestational diabetes, and the female offsprings born to diabetic mothers are also at increased risk of developing gestational diabetes themselves. This suggests that prolactin signaling regulates pancreatic beta-cell development, and it may contribute to fetal programming of pancreatic islets. Our current research focus is on 1) identification of novel signalling pathways that regulates β-cell function and survival during pregnancy, 2) identification of non-cell autonomous function of prolactin receptor in β-cell function, 3) mechanism underlying fetal programming of β-cells in the context of prenatal exposure to mild hyperglycemia. We use transgenic mice and cell lines as our model systems, using molecular biology, biochemistry, and in vivo physiologic testing techniques to address these questions.