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Glucose-dependent insulinotropic polypeptide (GIP) + xenin-25 is an investigational combination therapy being studied for its effects on insulin secretion and glucose regulation. GIP is a 42-amino acid hormone produced by intestinal K-cells that normally potentiates glucose-stimulated insulin secretion, while xenin-25 is a 25-amino acid neurotensin-related peptide that amplifies GIP-mediated insulin secretion. In type 2 diabetes, the insulinotropic effect of GIP is blunted, and xenin-25 has been shown to help restore this response. The combination works synergistically to reduce hyperglycemia more effectively than either peptide alone. In mice, xenin-25 appears to activate a cholinergic relay to islets, though the mechanism in humans may differ. This combination represents a novel approach to overcome GIP resistance in type 2 diabetes.
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