The present study is aimed at investigating the effect of acute and chronic colchicine administration on insulin secretion in humans. Acute insulin response to glucose (0.33 g/kg) was significantly decreased by colchicine (3 mg i.v.). In fact, this response (mean change 2-10 min insulin) was 44 +/- 8 microunits/ml before and 32 +/- 6 microunits/ml after colchicine administration (P less than 0.01). As a consequence of this, glucose disappearance rates were reduced (P less than 0.05). Infusion of lysine acetylsalicylate (LAS), an inhibitor of endogenous PG synthesis, completely reversed the inhibitory effect of colchicine upon insulin secretion and also augmented acute insulin response to glucose (response before colchicine + LAS = 45 +/- 8 microunits/ml; response after colchicine + LAS = 51 +/- 9 microunits/ml, P less than 0.05). This effect was associated with an increase in glucose disappearance rates (P less than 0.05). The 10-day treatment with colchicine (2 mg daily) caused a significant suppression of insulin secretion induced by oral glucose (100 g) and significantly increased the plasma glucose concentrations following the test (P less than 0.05). These findings demonstrate that (1) both acute and chronic colchicine administration inhibit glucose-induced insulin secretion and deteriorate glucose tolerance in humans, and (2) LAS completely reverses these negative effects of colchicine. An increased synthesis of endogenous PGE, which are known to inhibit insulin secretion in humans, might account for the inhibiting effect of colchicine on insulin secretion.