GIP and its receptor
The other incretin hormone — long overshadowed by GLP-1, now central to combination approaches.
Glucose-dependent insulinotropic hormone (GIP) is the first incretin to have been identified and, for a long time, the less interesting one. Released from intestinal K-cells, it amplifies insulin secretion much as GLP-1 does, but its insulinotropic action appeared markedly blunted in type 2 diabetes, so it was largely set aside as a target.
That judgement has been revisited. GIP receptors are expressed not only in the pancreas but in adipose tissue and the brain, and GIP signalling appears to contribute to energy balance through routes distinct from GLP-1. The clearest evidence is empirical: adding GIP receptor agonism to GLP-1 agonism produces greater metabolic effects than GLP-1 alone, which is the basis of Dual GIP/GLP-1 receptor agonists.
Its precise contribution remains genuinely debated — including whether receptor agonism or antagonism is the more useful direction, a live question in the literature. It is a good example of a target whose story reversed on evidence. See The incretin effect for the underlying physiology.
Related articles
- MetabolicThe incretin effectThe observation that started incretin science: glucose taken by mouth triggers far more insulin than the same glucose given intravenously.
- MetabolicGLP-1 receptor agonistsHow GLP-1 works, and why molecules mimicking it became central to metabolic research.
- MetabolicDual GIP/GLP-1 receptor agonistsEngineering one molecule to engage two incretin receptors — and what head-to-head data showed.
- MetabolicTriple agonists: GLP-1, GIP, and glucagonAdding glucagon receptor activity to incretin agonism — using a hormone long considered the opposition.
- MetabolicGastric emptying and satiety signalingThe gut-brain routes through which incretin signaling reduces food intake.
- MetabolicMetabolic syndromeThe cluster of findings — central adiposity, dysglycaemia, dyslipidaemia, raised blood pressure — that tend to travel together.