Reduced circulating sphingolipids and <i>CERS2</i> activity are linked to T2D risk and impaired insulin secretion.

ABSTRACT: Gestational diabetes mellitus (GDM), a transient form of diabetes that resolves postpartum, is a major risk factor for type 2 diabetes (T2D) in women. While the progression from GDM to T2D is not fully understood, it involves both genetic and environmental components. By integrating clinical, metabolomic, and genome-wide association study (GWAS) data, we identified associations between decreased sphingolipid biosynthesis and future T2D, in part through the rs267738 allele of the CERS2 gene in Hispanic women shortly after a GDM pregnancy. To understand the impact of the CERS2 gene and risk allele on glucose regulation, we examined whole-body Cers2 knockout and rs267738 knock-in mice. Both models exhibited glucose intolerance and impaired insulin secretion

SUBMITTER: Khan SR 

PROVIDER: S-EPMC11790001 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature