P&F Funds: Regulation of Pancreatic Beta Cell Mass by Adipose Lipoprotein Lipase

A transgenic mouse that expresses lipoprotein lipase in specifically in adipose tissue by the adiponectin promoter (AdipoQ]LpL) has improved glucose tolerance in diet induced obesity. Gene set enrichment analysis of microarray data of the adipose tissue of these mice revealed that a gene set for pancreatic beta cells is induced in the adipose tissue of the AdipoQ]LpL mice. One interpretation of this is that LpL upregulates secreted proteins that influence pancreatic beta cell development, and that these proteins can cause adipose tissue stem cells to express pancreatic beta cell genes. If this causes beta cell mass to increase in the pancreas, there would be increased insulin secretion in response to glucose. Preliminary analysis of a cohort of AdipoQ]LpL mice challenged with high fat diet for 16]weeks indicates increased pancreatic islet mass. The goals of this pilot grant are therefore to determine whether AdipoQ]LpL mice have increased insulin secretion in response to glucose and to comprehensively characterize pancreatic beta cells. This data will allow us to screen our microarray data to identify the proteins that cause this affect. Understanding this pathways the regulate beta cell mass may allow for the development of new treatments for type 2 diabetes.