AJP - Endocrinology and Metabolism, Vol 245, Issue 4 391-E400, Copyright © 1983 by American Physiological Society
Differential effects of microtubule-altering agents on beta-cells during development
R. S. Hill and W. B. Rhoten
The effect of microtubule-altering agents on the insulin secretory response
to glucose during the perinatal period was investigated with an in vitro
perifusion system. Rat pancreatic mince from day 17 of gestation (D17G) to
day 6 postnatally (D6PN) were perifused for 60 min in basal glucose
followed by 45 min with high glucose (3.5 mg/ml) or with high glucose plus
10 mM arginine (D17G). The two phases of insulin secretion in response to
high glucose developed in an age-dependent and asynchronous manner. The
first phase matured between D17G and D18G, and maturation of the second
phase occurred subsequently. Vinblastine (VB) (20 or 100 microM) had a
differential effect on the insulin secretory response. VB did not inhibit
stimulated insulin release at D17G. This absence of an inhibitory effect of
VB at D17G could not be explained by the absence of polymerized tubulin
because microtubules were present in the control beta-cells and, in
addition, VB treatment resulted in the formation of paracrystalline
deposits. Subsequently in development, and with isolated islets of the
adult, VB inhibited stimulated insulin release. Heavy water (deuterium
oxide, D2O) inhibited stimulated insulin secretion at D17G but blocked
completely insulin release from the near-term beta-cell. The inhibition of
insulin secretion by D2O was rapidly reversed when water replaced D2O in
the perifusion media. The results indicate that the maturation of the
second phase of insulin secretion coincides with the ability of the
microtubule-altering agents to modify the insulin secretory response. One
possible explanation for these findings is that at D17G the microtubules
are not coupled physicochemically to other molecules or structures
necessary for their role in insulin secretion to be expressed fully.
