Hypoxia-inducible factor-1 mediates pancreatic β-cell dysfunction by intermittent hypoxia.

ABSTRACT: The role of hypoxia-inducible factor (HIF)-1 in pancreatic β-cell response to intermittent hypoxia (IH) was examined. Studies were performed on adult wild-type (WT), HIF-1α heterozygous (HET), β-cell-specific HIF-1^-/- mice and mouse insulinoma (MIN6) cells exposed to IH patterned after blood O₂ profiles during obstructive sleep apnea. WT mice treated with IH showed insulin resistance, and pancreatic β-cell dysfunction manifested as augmented basal insulin secretion, and impaired glucose-stimulated insulin secretion and these effects were absent in HIF-1α HET mice. IH increased HIF-1α expression and elevated reactive oxygen species (ROS) levels in β-cells of WT mice. The elevated ROS levels were due to transcriptional upregulation of NADPH oxidase (NOX)-4 mRNA,

SUBMITTER: Wang N 

PROVIDER: S-EPMC7789966 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature