Pancreatic β cells are important targets for the diabetogenic effects of glucocorticoids

Franck Delaunay, Akhtar Khan, Antonio Cintra, Behrous Davani, Zong Chao Ling, Arne Andersson, Claes Göran Östenson, Jan Åke Gustafsson, Suad Efendic, Sam Okret

Research output: Contribution to journalArticle

246 Scopus citations

Abstract

Abnormalities contributing to the pathogenesis of non-insulin-dependent diabetes mellitus include impaired β cell function, peripheral insulin resistance, and increased hepatic glucose production. Glucocorticoids are diabetogenic hormones because they decrease glucose uptake and increase hepatic glucose production. In addition, they may directly inhibit insulin release. To evaluate thai possible role of glucocorticoids in β cell function independent of their other effects, transgenic mice with an increased glucocorticoid sensitivity restricted to their β cells were generated by overexpressing the glucocorticoid receptor (GR) under the control of the insulin promoter. Intravenous glucose tolerance tests showed that the GR transgenic mice had normal fasting and postabsorptive blood glucose levels but exhibited a reduced glucose tolerance compared with their control littermates. Measurement of plasma insulin levels 5 min after intravenous glucose load demonstrated a dramatic decrease in acute insulin response in the GR transgenic mice. These results show that glucocorticoids directly inhibit insulin release in vivo and identify the pancreatic β cell as an important target for the diabetogenic action of glucocorticoids.

Original languageEnglish (US)
Pages (from-to)2094-2098
Number of pages5
JournalJournal of Clinical Investigation
Volume100
Issue number8
DOIs
StatePublished - Oct 15 1997

Keywords

  • Glucocorticoid receptor
  • Glucocorticoid sensitivity
  • Insulin release
  • Non- insulin-dependent diabetes mellitus
  • Transgenic mice

ASJC Scopus subject areas

  • Medicine(all)

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