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NATIVE HORMONES · NATIVE HORMONE

GLP-1

ALSO KNOWN AS · Glucagon-like peptide-1 · Proglucagon 78–108

The incretin hormone the entire drug class is built around. Released by intestinal L-cells after eating, GLP-1 amplifies glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying and increases satiety.

Biology

GLP-1 is cleaved from proglucagon in enteroendocrine L-cells of the distal small intestine and colon, and released within minutes of nutrient arrival. It binds the GLP-1 receptor, a class B G-protein-coupled receptor expressed in pancreatic beta cells, the stomach, the vagus nerve and several hypothalamic and brainstem nuclei.

Receptor activation raises intracellular cAMP and potentiates insulin release only when glucose is elevated. That glucose dependence is why GLP-1 signalling carries a far lower intrinsic hypoglycaemia risk than sulfonylureas or exogenous insulin.

Why analogues exist

Native GLP-1 is destroyed by dipeptidyl peptidase-4 (DPP-4) within about two minutes, which makes the hormone itself useless as a medicine. Every approved drug in this class is an engineered analogue that resists DPP-4 cleavage and binds albumin or a carrier to stretch the half-life from minutes to days.

PRIMARY SOURCES

  1. 01Physiology of GLP-1Physiological Reviews
  2. 02Incretin biology overviewCell Metabolism

Educational reference only. Trial figures are protocol-condition means, not individual predictions. Investigational compounds are not approved medicines and have no legitimate consumer supply route.