Jpn. J. Pharmacol. 74 (2), 203-208 (1997)
Modulation of Tyrosine Kinase Activity Has Multiple Actions on Insulin
Release from the Pancreatic beta-Cell: Studies with Lavendustin A
Mitsuro Hisatomi (1), Tetsuo Hayakawa (1), Hiroyoshi Hidaka (2) and Ichiro
Niki (2,*)
(1) Second Department of Internal Medicine, (2) Department of Pharmacology,
Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya
466, Japan
(*) To whom correspondence should be addressed.
Abstract: We investigated the role of tyrosine kinases in the
regulation of insulin release from a hamster beta-cell line, HIT T15, using
selective tyrosine kinase inhibitors. Genistein increased the insulin release
induced by glucose, but herbimycin A, tyrphostins and the erbstatin analogue
failed to change the release. Lavendustin A at 0.1 nM - 1 microM caused
a concave-shaped inhibition of the insulin release stimulated by 7 mM glucose.
The inhibitory effect of lavendustin A was overcome by higher concentrations
of glucose. Lavendustin B, the negative control analogue, had no effect
on the release. Lavendustin A at a nanomolar range progressively inhibited
insulin release by high K+ (50 mM)-depolarization, whereas the inhibitor
did not change the insulin release by Ca2+ ionophore (A23187). On the contrary,
lavendustin A at 10 nM significantly increased insulin release when glucose-induced
insulin release was enhanced by either 5 microM forskolin or 162 nM 12-O-tetradecanoylphorbol
13-acetate. Lavendustin A failed to influence the Ca2+-induced insulin release
from HIT cells permeabilized with streptolysin-O. These findings suggest
that tyrosine kinases may play versatile roles in the control of insulin
release from the pancreatic beta-cell.
Keywords: Insulin release, Tyrosine kinase, Pancreatic beta-cell, Lavendustin
A, Tyrosine kinase inhibitor
Copyright© The Japanese Pharmacological Society 1997
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