Dissociation of the effects of vincristine on stimulated insulin release and the pancreatic beta-cell microtubular structures in the intact rat.

Abstract

We have recently shown that in the intact rat, at 10 min after vincristine treatment, glucose-induced insulin release and glucose tolerance were potentiated, but at 60 and 120 min after vincristine treatment, glucose- induced insulin release and glucose tolerance were significantly impaired. The present study further evaluated the mechanisms of these observations by examining the in vivo effect of vincristine on (1) the pancreatic β-cell microtubular structures and (2) insulin release in response to arginine, an insulin secretogogue other than glucose. In the first series of studies, the pancreases were removed from the rats at 60 and 120 min after vincristine (0.15 mg/kg; i.v.) or vehicle (control) administration for electron microscopy. Morphometric analysis revealed that the number of β- cell microtubules was similar in the vincristinetreated and the control rats. Furthermore, the mean microtubular length in vincristine-treated rats was also similar to that observed in the control rats. In the next series of studies, at 10, 60, or 120 min after vincristine (0.15 mg/kg; i.v.), insulin levels in response to an i.v. arginine pulse were similar in the vincristinetreated and in the control rats at all time intervals between 2 and 30 min. A parallel study once again demonstrated that glucose-induced insulin release and glucose tolerance were significantly impaired at 120 min after vincristine treatment. These findings indicate that (1) In the intact rat, inhibition of glucose-induced insulin release by vincristine occurs in the absence of any demonstrable changes in the β-cell microtubular structure; and (2) even though vincristine inhibits glucose-induced insulin release, it has no effect on arginine-induced insulin release. Therefore, in the intact rat, the inhibition of glucose-induced insulin release by vincristine may be mediated via mechanisms other than microtubular disruption.