Insulin synthesis and secretion (GSIS)

Insulin synthesis and secretion is the fundamental physiological process by which pancreatic beta-cells produce the hormone insulin and release it into the systemic circulation to regulate glucose levels. This multi-step process begins with the transcription of the INS gene and translation of preproinsulin, which is subsequently processed in the endoplasmic reticulum and Golgi apparatus into mature insulin and C-peptide. Secretion is primarily triggered by rising blood glucose levels; glucose enters beta-cells via transporters and is metabolized to increase the cellular ATP/ADP ratio, leading to the closure of ATP-sensitive potassium (K-ATP) channels. This closure causes membrane depolarization, opening voltage-gated calcium channels and inducing the calcium-dependent exocytosis of insulin-containing granules. Pharmacological modulation of this pathway is a cornerstone of type 2 diabetes treatment, with drugs like sulfonylureas directly stimulating secretion and incretin-based therapies enhancing the process in a glucose-dependent manner.

Other names

Glucose-stimulated insulin secretionGSISInsulin releaseBeta-cell secretory functionInsulinogenesisPancreatic insulin secretion

Modulation of the insulin release pathway via inhibition of ATP-sensitive potassium channels, activation of the glucagon-like peptide 1 (GLP-1) receptor, or inhibition of the dipeptidyl peptidase-4 (DPP-4) enzyme.