Insulin: The Receptor and Signaling Pathways

The insulin receptor belongs to the receptor tyrosine kinase family. It comprises disulfide-linked α/β dimers, forming a transmembrane heterotetramer.

It is highly abundant in adipocytes, skeletal muscle, and hepatocytes.

Insulin binding to the α subunits stimulates the β subunit's tyrosine kinase activity, allowing them to phosphorylate each other, leading to receptor activation.

The activated insulin receptor phosphorylates specific intracellular proteins such as Shc and IRS, which interact with downstream effectors like MAP kinase and PI3-kinase, respectively, contributing to cell growth, differentiation, and survival.

Additionally, the PI3-kinase-IRS interaction generates PIP3, which activates and anchors Akt in the membrane, promoting signaling events for GLUT4 membrane translocation, which facilitates excess glucose influx into insulin-responsive tissues such as adipocytes, and skeletal muscle.

The internalized glucose phosphorylates to glucose-6-phosphate, entering the glycolytic or pentose phosphate pathway. Glucose-6-phosphate can also be isomerized to glucose-1-phosphate and stored as glycogen.