Heterogenous impairment of α cell function in type 2 diabetes is linked to cell maturation state.

ABSTRACT: In diabetes, glucagon secretion from pancreatic α cells is dysregulated. The underlying mechanisms, and whether dysfunction occurs uniformly among cells, remain unclear. We examined α cells from human donors and mice using electrophysiological, transcriptomic, and computational approaches. Rising glucose suppresses α cell exocytosis by reducing P/Q-type Ca²⁺ channel activity, and this is disrupted in type 2 diabetes (T2D). Upon high-fat feeding of mice, α cells shift toward a "β cell-like" electrophysiological profile in concert with indications of impaired identity. In human α cells we identified links between cell membrane properties and cell surface signaling receptors, mitochondrial respiratory chain complex assembly, and cell maturation. Cell-type classification using machi

SUBMITTER: Dai XQ 

PROVIDER: S-EPMC8852281 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature