Single-cell decoding of human islet cell type-specific alterations in type 2 diabetes reveals converging genetic- and state-driven β -cell gene expression defects.

ABSTRACT: Pancreatic islets maintain glucose homeostasis through coordinated action of their constituent endocrine and affiliate cell types and are central to type 2 diabetes (T2D) genetics and pathophysiology. Our understanding of robust human islet cell type-specific alterations in T2D remains limited. Here, we report comprehensive single cell transcriptome profiling of 245,878 human islet cells from a 48-donor cohort spanning non-diabetic (ND), pre-diabetic (PD), and T2D states, identifying 14 distinct cell types detected in every donor from each glycemic state. Cohort analysis reveals ~25-30% loss of functional beta cell mass in T2D vs. ND or PD donors resulting from (1) reduced total beta cell numbers/proportions and (2) reciprocal loss of 'high function' and gain of senescent β -cell subpopula

SUBMITTER: Bandesh K 

PROVIDER: S-EPMC11785113 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature