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n-pyroglutamyl glucose-dependent insulinotropic polypeptide (pGlu-GIP) is a synthetic, N-terminally modified analogue of the native incretin hormone glucose-dependent insulinotropic polypeptide (GIP). Developed primarily by researchers at Ulster University, this biologic peptide was designed to resist degradation by dipeptidyl peptidase IV (DPP-IV), an enzyme that rapidly inactivates native GIP. By incorporating a pyroglutamyl group at the N-terminus, the compound exhibits significantly improved plasma stability, maintaining integrity for over 24 hours compared to the 2.3-hour half-life of native GIP. pGlu-GIP functions as a potent agonist of the GIP receptor, stimulating the production of cyclic adenosine 3'5' monophosphate (cAMP) and promoting glucose-dependent insulin secretion from pancreatic beta cells. Preclinical evaluations in obese diabetic (ob/ob) mice have shown that pGlu-GIP effectively lowers blood glucose levels and enhances the insulin response, positioning it as a research candidate for the treatment of type 2 diabetes mellitus.
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