We have created a mouse model for identifying genes that determine whether obesity will result in diabetes. Through a genome-wide mapping study, we mapped several gene loci that contribute to diabetes and to obesity. Interestingly, the obesity loci influence the penetrance of the diabetes loci. We are using the genetics to reveal new biochemical mechanisms underlying the key features of diabetes. This involves the positional cloning of the relevant gene loci and biochemical studies to elucidate the molecular basis of insulin resistance and beta-cell failure.
Lipoproteins package water-insoluble lipids for transport through the bloodstream.
Overproducation of lipoproteins is the leading cause of hyperlipidemia, a major risk factor for premature heart disease. Lipoproteins are constitutively synthesized. This finding opens many new questions relating to lipoprotein trafficking through the secretory pathway. Cells take up cholesterol through receptor-mediated endocytosis of plasma lipoproteins. To get rid of cholesterol, cells must efflux cholesterol back to lipoprotein acceptors.