Hepatic Regulation of Insulin Signal in IRKO models.

Autor: Donadel, Giulia, Capuani, Barbara, Bova, Luca, Biroccio, Antonino, Bartolini, Barbara, Urbani, Andrea, Federici, Massimo, Sbraccia, Paolo, Lauro, Davide
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Zdroj: Diabetes; Jun2007 Supplement 1, Vol. 56, pA663-A663, 1/4p
Abstrakt: In the western society and developing countries the incidence of insulin resistance, type-2 diabetes mellitus (T2DM) and augmented metabolic risk for cardiovascular disease and T2DM, are increasing exponentially. This raise is due mainly to an urbanized life style and to age of population. The shared feature of these related diseases is an impaired response to insulin target tissues, insulin resistance, and/or reduction of insulin secretion in pancreatic beta cells. Studies of these aspects are performed in vitro: culture cell lines of fibroblasts/hepatocytes derived from insulin receptor knockout (IRKO) mice transformed by adenovirus SV40; and ex vivo: in genetically modified animal (mouse) models for insulin receptor knockout (IRKO). It has been analyzed the differences in proteins expression profile and insulin signaling transmission in IRKO hepatocytes and IRKO mouse liver tissues compared with the wild type and heterozygous phenotypes. The aims of this study are to detect differences in proteins expression that could be modulated by insulin and could be involved in cell survival, cell cycle and oxidative stress. The in vitro cell line model is important to study the different modulation in activity and expression of insulin related substrates (basal conditions). The study performed in mouse model (ex-vivo) is relevant to detect differences in insulin substrates expression and activation in diabetic ketoacidotic conditions (pathophysiological conditions). To isolate the differentially expressed proteins we used 2D-PAGE analysis of protein extracts of knockout, wild type and heterozygous mouse liver tissues and murine hepatocytes phenotypes (wild type and knockout). Five proteins at present, of the 22 proteins differentially expressed, have been identified by mass spectrometry. We have also discovered a defect in post-transcription proteins production that it is associated with a related increases in mRNA levels and, again, we described a defect in myotubules proteins expression, but, differently, not in albumin production. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index