Islet O-GlcNAcylation Is Required for Lipid Potentiation of Insulin Secretion through SERCA2.

ABSTRACT: During early obesity, pancreatic β cells compensate for increased metabolic demand through a transient phase of insulin hypersecretion that stabilizes blood glucose and forestalls diabetic progression. We find evidence that β cell O-GlcNAcylation, a nutrient-responsive post-translational protein modification regulated by O-GlcNAc transferase (OGT), is critical for coupling hyperlipidemia to β cell functional adaptation during this compensatory prediabetic phase. In mice, islet O-GlcNAcylation rises and falls in tandem with the timeline of secretory potentiation during high-fat feeding while genetic models of β-cell-specific OGT loss abolish hyperinsulinemic responses to lipids, in vivo and in vitro. We identify the endoplasmic reticulum (ER) Ca²⁺ ATPase SERCA2 as a β cell O-GlcN

SUBMITTER: Lockridge A 

PROVIDER: S-EPMC8114475 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature