Genetic basis of susceptibility to type 2 diabetes.
Pancreatic alpha and beta cells secrete glucagon and insulin respectively to maintain glucose homeostasis. In conditions that impair the signaling of these hormones, alpha and beta cells compensate by increasing their number and augmenting their secretion. Defects in the compensatory responses lead to defects in glucose homeostasis. The molecular mechanisms underlying the compensatory responses remain incompletely understood. The Chen laboratory found that compensatory responses of pancreatic alpha cells and beta cells is conserved in zebrafish, a vertebrate model amenable for live imaging as well as large-scale genetic and chemical screens. We combine genetic, pharmacological, and imaging techniques to identify genes essential for the compensatory responses and to define their roles in diabetes.