Sirt1 Mediates Vitamin D Deficiency-Driven Gluconeogenesis in the Liver via mTorc2/Akt Signaling.

ABSTRACT: As an active form of vitamin D (VD), 1,25-dihydroxyvitamin D (1,25(OH)₂D₃) is involved in the development of many metabolic diseases, such as diabetes, autoimmune diseases, and tumours. While prospective epidemiological studies have consistently implicated VD deficiency in the regulation of glucose metabolism and insulin sensitivity, the specific mechanism remains unclear. Here, we generated 1α(OH)ase-null mice (targeted ablation of the 25-hydroxyvitamin D 1α hydroxylase enzyme) and found that these mice developed hepatic glucose overproduction, glucose intolerance, and hepatic insulin resistance accompanied by reduced Sirtuin 1 (Sirt1) expression. The chromatin immunoprecipitation (ChIP) and a luciferase reporter assay revealed that 1,25(OH)₂

SUBMITTER: Yuan Q 

PROVIDER: S-EPMC8817869 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature