Allosteric modulation of β-cell M₃ muscarinic acetylcholine receptors greatly improves glucose homeostasis in lean and obese mice.

ABSTRACT: Given the global epidemic in type 2 diabetes, novel antidiabetic drugs with increased efficacy and reduced side effects are urgently needed. Previous work has shown that M₃ muscarinic acetylcholine (ACh) receptors (M3Rs) expressed by pancreatic β cells play key roles in stimulating insulin secretion and maintaining physiological blood glucose levels. In the present study, we tested the hypothesis that a positive allosteric modulator (PAM) of M3R function can improve glucose homeostasis in mice by promoting insulin release. One major advantage of this approach is that allosteric agents respect the ACh-dependent spatiotemporal control of M3R activity. In this study, we first demonstrated that VU0119498, a drug known to act as a PAM at M3Rs, significantly augmented ACh-induced insu

SUBMITTER: Zhu L 

PROVIDER: S-EPMC6744902 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature