MRPS6 modulates glucose-stimulated insulin secretion in mouse islet cells through mitochondrial unfolded protein response.

ABSTRACT: Lack of efficient insulin secretion from the pancreas can lead to impaired glucose tolerance (IGT), prediabetes, and diabetes. We have previously identified two IGT-associated single nucleotide polymorphisms (SNPs) rs62212118 and rs13052524 located at two overlapping genes: MRPS6 and SLC5A3. In this study, we show that MRPS6 but not SLC5A3 regulates glucose-stimulated insulin secretion (GSIS) in primary human β-cell and a mouse pancreatic insulinoma β-cell line. Data mining and biochemical studies reveal that MRPS6 is positively regulated by the mitochondrial unfolded protein response (UPR^mt), but feedback inhibits UPR^mt. Disruption of such feedback by MRPS6 knockdown causes UPR^mt hyperactivation in high glucose conditions, hence elevated ROS levels, increa

SUBMITTER: Lin D 

PROVIDER: S-EPMC10533529 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature