Fig. 2

Schematic representation of the glucose–insulin signaling pathway. Binding of insulin to its receptor (IR) stimulates activation of downstream PI3K/Akt cascade. Activation of Akt by insulin results in glycogen synthesis and gluconeogenesis through GSK3 and FoxO1, respectively. ENPP1 interacts with Insulin receptor and inhibits its kinase activity. The GCK phosphorylates glucose in the hepatocyte to G6P and allows glucose to enter the cell. During glycolysis which is regulated by GCKR through inhibiting GCK, pyruvate is generated and transported to the mitochondria where it is decarboxylated to acetyl-CoA leading to de novo lipogenesis. The activity of SREBP1c is upregulated by insulin signaling, whereas ChREBP has been identified as a glucose-activated transcription factor, both of which contribute to de novo lipogenesis and fatty acid synthesis. During DNL, the ACC enzyme converts acetyl-CoA to malonyl-CoA, and then the FASN enzyme produces SFAs. Additionally, SCD1 transforms SFAs into MUFA, which is used as a substrate for the production of fatty acids. FOXO1 Forkhead box protein O1, PI3K phosphatidyl inositol 3-kinase, AKT AKT serine/threonine kinase 1, GS glycogen synthase, G6P glucose-6-phosphate, GCK glucokinase, GCKR glucokinase regulator, ChREBP carbohydrate-response element-binding protein, SREBP1 sterol regulatory element-binding protein 1, FASN fatty acid synthase, SCD1 stearoyl-coa desaturase 1, MUFA monounsaturated fatty acids, SFA saturated fatty acid, ACC acetyl-CoA carboxylase