25.2 : Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.

Insulin and C-peptide are co-secreted in equimolar quantities. While insulin has a half-life of 5-6 minutes due to extensive hepatic clearance, C-peptide, with no known physiological function or receptor, has a half-life of about 30 minutes. The β cell also synthesizes and secretes Islet Amyloid Polypeptide (IAPP) or amylin, a peptide that affects gastrointestinal motility and the speed of glucose absorption. Pramlintide, a drug used in diabetes treatment, mimics the action of IAPP.

Insulin secretion is tightly regulated to maintain stable blood glucose concentrations during fasting and feeding. This regulation is achieved by interacting with various nutrients, gastrointestinal hormones, pancreatic hormones, and autonomic neurotransmitters. Glucose, amino acids, fatty acids, and ketone bodies promote insulin secretion. GLUT1 mediates glucose uptake in human β cells, leading to glucose phosphorylation and ATP production. As a result, the K_ATP channel closes, promoting Ca²⁺ influx and insulin exocytosis. Glucagon from α cells counteracts insulin, maintaining glucose homeostasis.

Both adrenergic and cholinergic nerves richly innervate the islets. Stimulation of α₂ adrenergic receptors inhibits insulin secretion, whereas β₂ adrenergic receptor agonists and vagal nerve stimulation enhance release. Various conditions such as hypoglycemia, hypoxia, exercise, and severe burns that activate the sympathetic branch of the autonomic nervous system suppress insulin secretion by stimulating α₂ adrenergic receptors.