Glucose but not Arginine Prevents the Inhibitory Effect of Vincristine on Glucose-induced Insulin Release

Abstract

SUMMARYWe have previously shown that in the intact rat: (1) the inhibition of glucose-induced insulin release caused by vincristine occurred in the presence or absence of morphologic disruption of the beta-cell microtubules; and (2) vincristine, however, failed to inhibit arginine-induced insulin release, even in the presence of a marked disruption of the beta-cell microtubules. The present study further evaluated the mechanism of inhibition of vincristine on glucose-induced insulin release in the intact rat. In the first series of studies, glucose (500 mg/kg) was infused over 1 min into fasting rats with indwelling vascular catheters. Five minutes later, vincristine (0.15 mg/kg i.v.) or vehicle (control) was injected. Sixty minutes after vincristine or vehicle treatment, insulin release in response to a 150-mg i.v. glucose pulse was examined. Serum insulin and glucose levels were similar at all time intervals in the vincristine-treated and the control rats. In the next series of studies, the experiments were repeated as above, except arginine (100 mg/kg), instead of glucose, was infused over 1 min before vincristine or vehicle treatment. In these studies, serum insulin in response to a glucose pulse was significantly inhibited in the vincristine-treated rats as compared with control rats. Therefore, in the intact rat, prior exposure to glucose but not arginine protected the beta-cell from the inhibitory effect of vincristine on glucose-induced insulin release. These findings, along with our previous observations, support the concept that arginine-induced insulin release is mediated via mechanisms other than those involved in glucose-induced insulin release and suggest that the in vivo effect of vincristine on glucose-induced insulin release is mediated via alteration of the beta-cell glucose receptors rather than microtubular structures. DIABETES

The effect of vincristine on parathyroid hormone release and on the parathyroid cell microtubular structures in the intact rat

“…For example, colchicine has been shown to affect concanavalin A receptors on white blood cells (Madyastha et al 1977). Dissociation of the effects of vincristine on the beta cell microtubular struc¬ tures and on the stimulated insulin release ob¬ served in our previous studies have shown that the effect of these agents on insulin release is mediated by mechanisms other than microtubular dis¬ ruption (Shah et al 1979(Shah et al , 1981(Shah et al , 1982a(Shah et al , 1982b). …”