Type 1 and type 2 diabetes are both characterized by a paucity of functional beta cell mass that leads to poor glycemic control and its attendant complications if untreated. Investigating the mechanism that promote beta cell proliferation and identifying growth factors that can selectively and safely enhance the numbers of glucose responsive insulin secreting beta cells is an area of timely and exciting research. In this context it is notable that mammals exhibit a remarkable ability to adapt to insulin resistance by enhancing their functional beta cells mass that likely delays the onset of overt diabetes. The factors and mechanism that underlie this adaptation is not very well understood. In this presentation the current concepts in inter-organ cross talk in models of insulin resistance with a focus on beta cell proliferation will be discussed.