Research
Hormonal
In type 2 diabetes, the insulinotropic effect of GIP is significantly reduced or absent, primarily due to hyperglycemia-induced downregulation and degradation of the GIP receptor (GIPR) on beta cells.
In type 2 diabetes, your body still makes GIP, but your insulin cells stop listening to it because high blood sugar damages the receptors. This is reversible: lowering your blood sugar with medication or lifestyle changes can restore your body's natural ability to respond to GIP.
StrongQualifiesHIGH confidence
the insulinotropic effect of GIP is strikingly reduced in people with T2D relative to healthy controls... the decreased incretin effect in patients with T2D is attributed mainly to an impaired insulinotropic action of GIP, potentially because of impaired b-cell function and downregulation, degradation or alternative splicing of the GIP receptor under conditions of hyperglycemia.
Why this rating
Supported by multiple studies showing receptor downregulation in hyperglycemic conditions and restoration upon glycemic normalization.
Source
Glucose-dependent insulinotropic polypeptide (GIP)
Timo D. Müller et al. · Molecular Metabolism · 2025
DOI 10.1016/j.molmet.2025.102118
narrative_reviewCited 58×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- GIP is the predominant incretin hormone in humans responsible for the majority of the incretin effect on postprandial insulin secretion, although its insulinotropic action is impaired in type 2 diabetes due to receptor downregulation.Strong
- GIP has pleiotropic effects beyond glucose metabolism, including potential benefits for obesity, bone health, and neurodegenerative disorders, making it a candidate for pharmacotherapies.Good
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