Insulin plays a key role in regulating energy metabolism and keeping plasma glucose concentrations under control. Insulin is secreted from pancreatic b-cell located on the islets of Langerhans in response to elevated plasma glucose levels in an oscillatory fashion with periods ranging from 2-10 minutes. Studies show that insulin oscillations increase the effectiveness of insulin, and insulin oscillations are lost in diabetic patients and their close relatives. Although the association between impaired insulin oscillations and diabetes is evident, the cause-consequence relation between them isn’t fully understood.
Insulin oscillations result from periodic electrical activity generated by pancreatic b-cells and their intra and inter-islet synchronization. The mechanism for inter-islet synchronization is not fully understood but intra-islet synchronization result from the gap-junctional connections between neighboring b-cells. Gap-junctional channels on pancreatic b-cells comprises primarily connexin36 proteins (cx36). The expression of cx36 protein is regulated by several factors including glucose. In this project, we investigate the bidirectional association between cx36 expression and the progression of diabetes via mathematical modeling and experimental procedures. In our lab, we develop physiologically based mathematical models of b-cell electrophysiology and insulin-glucose network to understand this bidirectional relation and test our model predictions in the lab.