Hyperglycemia-activated 11β-hydroxysteroid dehydrogenase type 1 increases endoplasmic reticulum stress and skin barrier dysfunction.

ABSTRACT: The diabetes mellitus (DM) skin shows skin barrier dysfunction and skin lipid abnormality, similar to conditions induced by systemic or local glucocorticoid excess and aged skin. Inactive glucocorticoid (GC) is converted into active glucocorticoid by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Hyperglycemia in DM and excessive GC are known to increase endoplasmic reticulum (ER) stress. We hypothesized that hyperglycemia affects systemic GC homeostasis and that the action of skin 11β-HSD1 and GC contributes to increased ER stress and barrier defects in DM. We compared 11β-HSD1, active GC, and ER stress between hyperglycemic and normoglycemic conditions in normal human keratinocytes and db/db mice. 11β-HSD1 and cortisol increased with time in keratinocyte culture under hyperglycemic

SUBMITTER: Lee YB 

PROVIDER: S-EPMC10244460 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature