The effects of dexamethasone on insulin release and biosynthesis are dependent on the dose and duration of treatment

Complex results concerning the effect of glucocorticoids on insulin secreti on have been reported. The aim of this study is to clarify the direct effec ts of glucocorticoids on pancreatic islets: and to determine whether the ef fect of glucocorticoids on insulin biosynthesis: or release is dependent on the dose and duration of treatment with glucocorticoid. Studies on insulin secretion and biosynthesis were performed. with different concentrations ( 0, 1, 10, 100 nmol/l) and durations (1 and 6 h) of treatment with dexametha sone (dexa) in rat pancreatic islets. (1) One nmol/l dexa had no inhibitory effect on insulin secretion and biosynthesis. Ten and 100 nmol/l had an in hibitory effect on insulin secretion, which was mainly due to suppression o f the first phase of insulin secretion. (2) Insulin content was: significan tly increased regardless of the concentration in I-h treated islets. Howeve r, insulin content was markedly diminished with 100 nmol/l dexa in 6-h trea ted islets. (3) The preproinsulin mRNA expression of 6-h treated islets was suppressed in a dose-dependent manner. Our data revealed that, in the cond ition of short-term and low-dose glucocorticoid exposure, insulin secretion and biosynthesis are not affected. The secretory process of insulin seems to be the initial step of the inhibitory action of glucocorticoid. Both ins ulin release and biosynthesis are inhibited by chronic exposure to high dos e dexamethasone. It can be concluded that glucocorticoid might be involved in the multisteps of insulin release and biosynthesis. (C) 2001 Elsevier Sc ience Ireland Ltd. All rights reserved.