Type 2 diabetes is characterized by insulin resistance and has been associated with increased lipids (fat) in the blood (hyperlipidemia). Our research focuses on regulation of blood lipid levels by controlling both intestinal and liver fat (lipid/lipoprotein) metabolism. We have previously shown in our laboratory that a naturally occurring hormone called glucagon-like peptide-1 (GLP-1) can lower intestinal lipoprotein production. The current research proposal will focus on analyzing the following three areas: 1) how intestinal inflammation alters intestinal lipoprotein production, 2) regulation of intestinal lipoprotein production through brain signaling, and 3) regulation of liver lipoprotein production in insulin resistance. Merck Pharma has developed a compound (sitaglipitin) that prevents the degradation of endogenous GLP-1. Analyzing the effects of long lasting GLP-1 signaling will provide crucial mechanistic insight into common disorders associated with hyperlipidemia.