Novel dual incretin agonist peptide with antidiabetic and neuroprotective potential

Biochemical Pharmacology
N M PathakPeter R Flatt

Abstract

Glucose-dependent insulinotropic hormone (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones that exert an array of beneficial actions on metabolism and cognitive function. GLP-1-based therapeutics have been highly successful in terms of obesity and diabetes management, however GIP therapies have found no clinical utility to date. In the present study we describe, for the first time, the therapeutic effectiveness of a novel GIP/GLP-1 hybrid peptide based on the amino acid sequences of GIP, GLP-1 and the clinically approved GLP-1 mimetic, exendin-4. The hybrid peptide, N-ac(d-Ala2)GIP/GLP-1-exe, was enzymatically stable for up to 12 h when incubated with DPP-4. N-ac(d-Ala2)GIP/GLP-1-exe significantly (P < 0.001) stimulated insulin secretion from BRIN-BD11 cells and isolated mouse islets, and evoked dose-dependent increases (P < 0.001) in cAMP production in both GIP-R and GLP-1-R transfected cells. In mice, injection of the hybrid in combination with glucose significantly (P < 0.001) reduced glucose and increased insulin concentrations, with metabolic actions evident (P < 0.05) 8 h post-injection. Twice-daily injection of N-ac(d-Ala2)GIP/GLP-1-exe to high fat fed (HFF) mice for 28 days significantly (P < 0.05-P < 0.00...Continue Reading

Citations

Mar 2, 2019·Expert Opinion on Drug Discovery·Mar QuiñonesOmar Al-Massadi
Apr 3, 2019·Brain Injury : [BI]·Damla ErbilHale Yapıcı Eser
May 20, 2020·Clinical Medicine Insights. Endocrinology and Diabetes·Andrew English, Nigel Irwin
Feb 29, 2020·Clinical Medicine Insights. Endocrinology and Diabetes·Annie Hasib
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Dec 19, 2020·Comprehensive Reviews in Food Science and Food Safety·Kong Fei ChaiWei Ning Chen
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Jun 1, 2021·Frontiers in Endocrinology·Seunghun P LeeAlessandro Pocai
Jul 3, 2021·Expert Opinion on Investigational Drugs·Jonathan FlintoffThomas Hj Burne

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