Figure 4.

Schematic representation of the links between obesity and insulin resistance and their internal mechanisms associated with T2DM. Free fatty acids (FFAs) and their metabolites activate protein kinase C and promote Ser/Thr phosphorylation of insulin receptor substrates 1 (IRS-1), in turn reducing normal Tyr phosphorylation of IRS-1 and impairing the control of the glucose transporter GLUT4, inducing insulin resistance and thus poor glucose tolerance. Proinflammatory cytokines secreted by adipose tissue activate the JNK signaling pathway and indirectly inhibit the translocation of GLUT4 to promote insulin resistance. Elevated leptin and low adiponectin levels, along with insulin resistance, impair β-cell function, suppressing insulin secretion and leading to T2DM. The black line indicates the normal mechanism underlying the insulin-stimulated uptake of glucose involving translocation of the glucose transporter GLUT4 to the plasma membrane. The purple line indicates the defective process(es) in obese individuals.