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Summer Student Opportunities Program Application Abstract

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Database mining of phenotype induced by high-fat diets

Gary Cline (New Haven, CT)

Summer Student Opportunities Program

The use of high-fat diets and genetically modified mice have become one of the principle research strategies used by the Mouse Metabolic Phenotyping Centers, and other researchers, to gain a better understanding of the mechanisms whereby lipid metabolism leads to peripheral and hepatic insulin resistance. However, it has become clear that all high-fat diets are not equal in causing insulin resistance, and that different fatty acids induce insulin resistance by different biochemical mechanisms. Another confounding factor is that different background strains can exhibit differences in their susceptibility to high-fat induced insulin resistance. Finally, the ability of the beta-cell to maintain glucose homeostasis in the insulin resistance is dependent on its resistance to compensate with increases in either mass and/or function, susceptibility to gluco-lipotoxity, and background strain. This proposal will use the MMPC database to address these questions in three aims. Specific Aim 1 is to use the database to determine the impact of different dietary lipids (i.e., saturated, unsaturated, chain length) of high-fat diets on the development of insulin resistance. Specific Aim 2 is to assess how different background strains differ in their susceptibility to develop insulin resistance when provided with commonly used high-fat diets.Specific Aim 3 is to evaluate whether the different in vivo and in vitro methods of assessing pancreatic islet ß-cell function provide similar measures of glucose-stimulated insulin secretion (GSIS) in healthy and diabetic mice.

No report available yet.

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