Trimethylguanosine synthase 1 is a novel regulator of pancreatic beta-cell mass and function.

ABSTRACT: Type 2 diabetes is a metabolic disorder associated with abnormal glucose homeostasis and is characterized by intrinsic defects in β-cell function and mass. Trimethylguanosine synthase 1 (TGS1) is an evolutionarily conserved enzyme that methylates small nuclear and nucleolar RNAs and that is involved in pre-mRNA splicing, transcription, and ribosome production. However, the role of TGS1 in β-cells and glucose homeostasis had not been explored. Here, we show that TGS1 is upregulated by insulin and upregulated in islets of Langerhans from mice exposed to a high-fat diet and in human β-cells from type 2 diabetes donors. Using mice with conditional (βTGS1KO) and inducible (MIP-Cre^ERT-TGS1KO) TGS1 deletion, we determined that TGS1 regulates β-cell mass and function. Using unbiased app

SUBMITTER: Blandino-Rosano M 

PROVIDER: S-EPMC8861161 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature