Effect of dexamethasone on insulin secretion: examination of underlying mechanisms.
OBJECTIVE
To study the mechanism of increased insulin secretion in response to short-term administration of dexamethasone.


METHODS
Male Wistar rats were injected intraperitoneally with dexamethasone (dexamethasone; 200 mcg/kg body weight per day) or saline for 3 consecutive days. Insulin secretion in response to glucose, ionomycin, and KCl was quantified in islets isolated from the animals, and the amount of glucokinase was measured by Western blot.


RESULTS
Dexamethasone-treated animals had 1.18-fold higher fasting blood glucose concentration and 6.5-fold increase in fasting serum insulin concentration compared with findings from animals injected with saline. Compared with islets isolated from control rats, islets from dexamethasone-treated rats secreted more insulin at 60 minutes in response to 5.5 mM glucose (416.4 vs 115.6 fmoles/10 islets, P = .011) and in response to 16.6 mM glucose (985.5 vs 520.6 fmoles/10 islets, P = .014); no change in insulin secretion was observed at 10 minutes. Insulin secretion from islets of dexamethasone-treated rats and control rats was not differentially augmented in response to either ionomycin or potassium chloride. Glucokinase expression was not altered by treatment with dexamethasone.


CONCLUSIONS
Augmentation of insulin secretion in response to glucose in the pancreatic islets from dexamethasone-treated rats is preserved in islets studied in vitro. The increase in glucose-stimulated insulin secretion appears to be mediated by steps upstream to β-cell membrane depolarization and the attended increase in intracellular calcium in the signaling pathway of insulin secretion.
Sood
Ajay
A
Division of Clinical and Molecular Endocrinology, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA. axs259@cwru.edu
Ismail-Beigi
Faramarz
F
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D055571:Secretory Pathway / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D007476:Ionophores; D015759:Ionomycin; D011189:Potassium Chloride; D003907:Dexamethasone