Endocrine Abstracts

Type 2 diabetes mellitus (T2DM) is characterized by major disturbances in lipids as well as the defining abnormalities in glucose. In spite of this, our understanding of the control of lipid metabolism is incomplete. In particular, the relative contribution of insulin compared to other regulatory inputs to the determination of liver and total body adiposity is unclear. We have used a loss of function approach to study the requirement for a major downstream target of insulin, the serine/threonine protein kinase Akt/PKB, in the control of lipid metabolism. We find that the presence of the Akt2 isoform is absolutely required for the accumulation of triglyceride in the livers of insulin resistant mice, and this is likely due to lack of increased de novo lipogenesis. These data indicate that the preservation of hepatic insulin signalling is a critical etiological factor in the development of metabolic syndrome or T2DM and serve to emphasis the selective insulin resistance that occurs in these diseases.