Insulin action and signalling in fat and muscle from dexamethasone-treated rats

Research output: Contribution to journalArticlepeer-review

Authors

Colleges, School and Institutes

External organisations

  • Umeå University Hospital
  • Natl. Inst. of Occupational Health

Abstract

Glucocorticoids initiate whole body insulin resistance and the aim of the present study was to investigate effects of dexamethasone on protein expression and insulin signalling in muscle and fat tissue. Rats were injected with dexamethasone (1 mg/kg/day, i.p.) or placebo for 11 days before insulin sensitivity was evaluated in vitro in soleus and epitrochlearis muscles and in isolated epididymal adipocytes. Dexamethasone treatment reduced insulin-stimulated glucose uptake and glycogen synthesis by 30-70% in epitrochlearis and soleus, and insulin-stimulated glucose uptake by ∼40% in adipocytes. 8-bromo-cAMP-stimulated lipolysis was ∼2-fold higher in adipocytes from dexamethasone-treated rats and insulin was less effective to inhibit cAMP-stimulated lipolysis. A main finding was that dexamethasone decreased expression of PKB and insulin-stimulated Ser473 and Thr308 phosphorylation in both muscles and adipocytes. Expression of GSK-3 was not influenced by dexamethasone treatment in muscles or adipocytes and insulin-stimulated GSK-3β Ser9 phosphorylation was reduced in muscles only. A novel finding was that glycogen synthase (GS) Ser7 phosphorylation was higher in both muscles from dexamethasone-treated rats. GS expression decreased (by 50%) in adipocytes only. Basal and insulin-stimulated GS Ser641 and GS Ser645,649,653,657 phosphorylation was elevated in epitrochlearis and soleus muscles and GS fractional activity was reduced correspondingly. In conclusion, dexamethasone treatment (1) decreases PKB expression and insulin-stimulated phosphorylation in both muscles and adipocytes, and (2) increases GS phosphorylation (reduces GS fractional activity) in muscles and decreases GS expression in adipocytes. We suggest PKB and GS as major targets for dexamethasone-induced insulin resistance.

Details

Original languageEnglish
Pages (from-to)91-101
Number of pages11
JournalArchives of Biochemistry and Biophysics
Volume474
Issue number1
Early online date29 Feb 2008
Publication statusPublished - 1 Jun 2008

Keywords

  • cAMP, Glucocorticoids, Glycerol, Lipolysis, Phosphorylation