Hormonal
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.
Your body naturally produces GIP, which is the main hormone helping your pancreas release insulin after eating. In type 2 diabetes, this GIP signal gets weaker because the receptors on your insulin-producing cells become less sensitive. This is why treatments that target both GIP and GLP-1 receptors are often more effective than targeting GLP-1 alone.
postprandial insulin secretion is lower upon antagonization of GIPR relative to GLP-1R, hence indicating that GIP is the predominant incretin hormone in humans [134] and mice [159].
Why this rating
Based on multiple human studies using specific antagonists and receptor knockouts cited in a high-impact review.
Source
Glucose-dependent insulinotropic polypeptide (GIP)
Timo D. Müller et al. · Molecular Metabolism · 2025
DOI 10.1016/j.molmet.2025.102118
More from this paper
- 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.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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