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Figure 1: Insulin-dependent and -independent regulation of glucidic and lipidic metabolism. In skeletal muscle, insulin and insulin-independent AMPK pathways regulate the translocation of GLUT4 vesicles to plasma membrane that results in stimulation of glucose uptake. In the liver, these pathways act in a concerted fashion to regulate glucose and lipid metabolism. AMPK activation leads to the inhibition of ACC activity thereby inhibiting fatty acid biosynthesis and increasing fatty acid oxidation. Moreover, the suppression of SREPB-1 by AMPK activation inhibits fatty acid synthesis through the downregulation of the lipogenic genes. On the other hand, insulin inhibits hepatic glucose production by suppressing genes encoding gluconeogenic enzymes including G6pase. Concomitantly, insulin enhances the storage of glucose as glycogen via the inhibition of GSK-3, thus relieving its inhibitory action on GS and leads to glycogen synthesis. Finally, insulin and AMPK pathways have opposing roles on adipose tissue metabolism. While Insulin-mediated Akt (PKB) phosphorylation stimulates the differentiation of adipocytes and the accumulation of fat, activation of AMPK has an inhibitory effect. Adipocyte differentiation is mediated, at least in part, through the induction of C/EBP-β. The latter promotes adipogenesis by upregulating the adipogenic transcription factors C/EBPα and PPAR-γ gene expression. ACC, acetyl-CoA carboxylase; AMPK, AMP-activated protein kinase; C/EBP, CCAAT-enhancer-binding protein; G6pase, glucose-6-phosphatase; GS, glycogen synthase; GSK-3, glycogen synthase kinase-3; PKB, protein kinase B; PPARγ, peroxisome-proliferator-activated receptor gamma; SREPB-1, sterol regulatory element-binding protein.