The effect of lithium on glucose- and tolbutamide-induced insulin release and glucose tolerance in the intact rat.

The effects of lithium on stimulus-induced insulin release and glucose tolerance were examined in intact, unanesthetized, and unrestrained rats with indwelling intravascular catheters. In the first study, a 150-mg iv glucose pulse was administered at 30 min after rapid iv injection of lithium carbonate (1 meq/kg) or vehicle. After the glucose pulse, mean serum glucose levels throughout the observation period were significantly greater in the lithium-treated rats than in the vehicle-treated (control) rats. Similarly, a mean glucose disappearance rate of 2.8 +/- 0.2%/min in the lithium-treated rats was significantly less (P < 0.02) than the mean glucose disappearance rate of 3.4 +/- 0.2%/min observed in the control rats. In response to glucose pulse, acute insulin release was significantly inhibited in the lithium-treated rats compared with that observed in the control rats. In the second study, a 10-mg tolbutamide pulse was administered 30 min after a rapid iv injection of lithium carbonate or vehicle. Acute insulin release in response to tolbutamide pulse was markedly inhibited in the lithium-treated rats compared with that observed in the control rats. In lithium-treated rats, the decline in serum glucose between 10-45 min after the tolbutamide pulse was significantly less than that observed in the control rats. Therefore, in the intact rat, lithium inhibits glucose- and tolbutamide-induced insulin release, which, in turn, causes glucose intolerance and prevents tolbutamide-induced hypoglycemia.