Nocturnal activation of melatonin receptor type 1 signaling modulates diurnal insulin sensitivity via regulation of PI3K activity.

ABSTRACT: Recent genetic studies have highlighted the potential involvement of melatonin receptor 1 (MT₁ ) and melatonin receptor 2 (MT₂ ) in the pathogenesis of type 2 diabetes. Here, we report that mice lacking MT₁ (MT₁ KO) tend to accumulate more fat mass than WT mice and exhibit marked systemic insulin resistance. Additional experiments revealed that the main insulin signaling pathway affected by the loss of MT₁ was the activation of phosphatidylinositol-3-kinase (PI3K). Transcripts of both catalytic and regulatory subunits of PI3K were strongly downregulated within MT₁ KO mice. Moreover, the suppression of nocturnal melatonin levels within WT mice, by exposing mice to constant light, resulted in impaired PI3K activity and insulin

SUBMITTER: Owino S 

PROVIDER: S-EPMC5843510 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature