Diabetes is defined by abnormalities in circulating substrates;glucose is obvious, but dyslipidemias also typify the condition. Central to the impairment of substrate metabolism is beta-cell dysfunction and resistance to insulin action. There have been significant advances in recent years that have increased our understanding of normal and abnormal beta-cell function and great progress has been made in elucidating the insulin-signaling pathway. However, much work remains before translation of these advances to human diabetes. Transgenic technology holds great promise for making these connections but requires precise and often sophisticated phenotypic characterization to maximize information gained from appropriate mouse models. It is also clear that abnormalities in the production and metabolism of lipids and lipoproteins are common in diabetes, that they interact with the processes governing glucose metabolism, and most importantly, that they are predisposing factors for cardiovascular disease, the primary cause of death in diabetic humans. To meet the goals of the UC MMPC as well as the MMPC Consortium, we will continue to focus on the phenotypic analysis of lipid, lipoprotein, and glucose metabolism in mouse models in order to assist investigators in gaining an understanding of the effects of specific genetic manipulations and their role in diabetes. Four broad, long-range goals of the Lipid, Lipoprotein, and Glucose Metabolism Core (Core C) have been established:
Specific Aim 1; To provide current state of the art phenotypic tests that allow investigators to characterize the lipid, lipoprotein, and glucose metabolism of their mice.
Specific Aim 2 : To advise investigators on the most appropriate tests, and the optimal sequence of tests, to meet specific goals of phenotypic characterization of their genetically modified mice, or how a physiological manipulation (e.g. chronic feeding of a high fat diet) modifies the response of the animal.
Specific Aim 3 : To train investigators in the performance of specialized procedures established and routinely practiced in the Core.
Specific Aim 4 : To improve current methods and develop new procedures and new approaches to study lipid and glucose metabolism in mice.
Because abnormalities in circulating substrates are the hallmark of the diabetic state, assessments of lipid and glucose metabolism have been one of the most common phenotypic requests from the UC MMPC. In addition, with the recent surge of interest in bariatric surgery and how it so rapidly reverses diabetes, we anticipate even more requests for determination of various lipid and peptide measurements.
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