Grant: Operating Grant

Increasing our understanding of how beta cells function and survive is critical to the improvement of treatment of type I and type II diabetes. While islet transplantation offers a promising treatment for Type I diabetes, this approach is limited by graft immune rejection and impaired function and survival of transplanted islets. We have found that the Lkb1 gene regulates many central beta cell functions, including insulin production and secretion. Loss of Lkb1 leads to beta cell proliferation, cell growth, and consequent protection from high fat diet induced diabetes due to an increase in the overall amount and fitness of the beta cell population. Lkb1 controls the activity of a family of 12 downstream 'switch' proteins, the so-called Ampk kinase family. We hope to delineate which Ampk family member(s) control which specific beta cell functions downstream of Lkb1, with a view to designing specific therapeutics for improving beta cell function (i.e. insulin secretion) and beta cell growth and survival. The knowledge gained will be applied to preserve islet cell survival during islet transplantation for children with Type I diabetes, and to improve islet cell function in Type II diabetes patients who display impaired glucose control.