α-CGRP disrupts amylin fibrillization and regulates insulin secretion: implications on diabetes and migraine.

ABSTRACT: Despite being relatively benign and not an indicative signature of toxicity, fibril formation and fibrillar structures continue to be key factors in assessing the structure-function relationship in protein aggregation diseases. The inability to capture molecular cross-talk among key players at the tissue level before fibril formation greatly accounts for the missing link toward the development of an efficacious therapeutic intervention for Type II diabetes mellitus (T2DM). We show that human α-calcitonin gene-related peptide (α-CGRP) remodeled amylin fibrillization. Furthermore, while CGRP and/or amylin monomers reduce the secretion of both mouse Ins1 and Ins2 proteins, CGRP oligomers have a reverse effect on Ins1. Genetically reduced Ins2, the orthologous version of human insulin, has bee

SUBMITTER: Gray ALH 

PROVIDER: S-EPMC8179678 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature