58. Mechanism of Action of Insulin and Growth Factors. Insulin Dependent Tissues and Insulin Dependent Transporter of Glucose

Mechanism of Action of Insulin and Growth Factors

• Insulin is a peptide hormone secreted by β-cells of the pancreatic islets in response to elevated blood glucose.
• Growth factors (e.g., IGF-1) are peptide/protein hormones that promote cell growth, proliferation, and differentiation.

Insulin Signaling Mechanism

• Insulin binds to insulin receptor, a tyrosine kinase receptor on the cell membrane.
• Receptor autophosphorylation occurs on tyrosine residues of the β-subunit.
• Activated receptor phosphorylates insulin receptor substrates (IRS proteins).
• IRS proteins trigger multiple intracellular signaling cascades:
• PI3K–AKT pathway → promotes glucose uptake, glycogen synthesis, protein synthesis, and lipogenesis.
• MAPK pathway → regulates gene expression, growth, and differentiation.

Insulin-Dependent Tissues

• Muscle: major site for glucose disposal; requires insulin for GLUT4 translocation.
• Adipose tissue: insulin stimulates glucose uptake, lipogenesis, and inhibits lipolysis.
• Liver: partially insulin-dependent; insulin stimulates glycogenesis, lipogenesis, and suppresses gluconeogenesis.
• Other tissues: brain, RBCs, and liver have insulin-independent glucose uptake.

Insulin-Dependent Glucose Transporters

• GLUT4: primary insulin-sensitive transporter in muscle and adipose tissue.
• Upon insulin stimulation, GLUT4-containing vesicles translocate to the plasma membrane → glucose uptake increases.
• GLUT1 and GLUT2: insulin-independent, found in RBCs, brain, liver, and pancreatic β-cells.