Imeglimin amplifies glucose-stimulated insulin release from diabetic islets via a distinct mechanism of action.

ABSTRACT: Pancreatic islet β-cell dysfunction is characterized by defective glucose-stimulated insulin secretion (GSIS) and is a predominant component of the pathophysiology of diabetes. Imeglimin, a novel first-in-class small molecule tetrahydrotriazine drug candidate, improves glycemia and GSIS in preclinical models and clinical trials in patients with Type 2 diabetes; however, the mechanism by which it restores β-cell function is unknown. Here, we show that imeglimin acutely and directly amplifies GSIS in islets isolated from rodents with Type 2 diabetes via a mode of action that is distinct from other known therapeutic approaches. The underlying mechanism involves increases in the cellular nicotinamide adenine dinucleotide (NAD+) pool-potentially via the salvage pathway and induction of nicotina

SUBMITTER: Hallakou-Bozec S 

PROVIDER: S-EPMC7894908 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature