The Lipogenic Effect of Insulin Revisited

Abstract

Insulin promotes lipogenesis and suppresses hepatic gluconeogenesis. Paradoxically, the positive effect of insulin on lipid production in liver is maintained under conditions of insulin resistance, unlike its defective action on gluconeogenesis. In this chapter, we revisit this gluconeogenesis-selectivity notion by reviewing evidence that in fact, under normo-insulinemic conditions, insulin acutely reduces de novo lipogenesis in liver. This is mediated by the ability of insulin pulses in portal vein to phosphorylate the Carcino-Embryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1), an abundant protein in liver that promotes hepatic insulin clearance in a phosphorylation-dependent manner. In the presence of sustained hyperinsulinemia, pulsatility of insulin release diminishes together with its signaling, giving way to its chronic positive effect on lipogenic genes transcription. This would set the stage to redefi ne hepatic insulin resistance as a comprehensive process that includes defective insulin action in glucose as well as lipid production. Keywords

Aquaporins in insulin resistance and diabetes: More than channels!

“…The effects of hyperinsulinemia bring to a dysregulation of the lipogenesis, which increases the production of VLDL and reduces the one of the HDL. This brings to an accumulation of plasma triglycerides and to a lower concentration of HDL-cholesterol [ 78 , 79 ].…”