DEXAMETHASONE PRETREATMENT OF RAT INSULINOMA CELLS DECREASES BINDING OF GLUCAGON-LIKE PEPTIDE-1(7-36)AMIDE

The effect of dexamethasone on binding of glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) to rat insulinoma-derived cells (RINm5F) was investigated. Preincubation of RINm5F cells with dexamethasone (100 nmol/l) for 24 h resulted in a decrease of GLP-1(7-36)amide binding to 55.0 ± 8.16% (mean ± S.E.M.), incubation for 48 h to 39.1 ± 1.76%, and for 72 h to 15.5 ± 4.35% of maximal binding. The GLP-1(7-36)amide-induced stimulation of cyclic AMP (cAMP) production was significantly decreased to 61.03 ± 7.4% of maximum production in cells pretreated with dexamethasone (100 nmol/l) for 48 h. The decreased binding was due to a reduction of the receptor number while the receptor affinity remained unchanged. These inhibitory effects of binding and cAMP formation induced by dexamethasone were completely abolished when the antiglucocorticoid RU 38486 (100 nmol/l) was added during preincubation with dexamethasone. RU 38486 alone had no effects. Our data suggest that the biological action of GLP-17(7-36)amide at the B-cell may be modified by glucocorticoids.