Tyrosine kinases play a permissive role in glucose-induced insulin secretion from adult rat islets

SJ Persaud, TE Harris, CJ Burns… - Journal of Molecular …, 1999 - jme.bioscientifica.com
SJ Persaud, TE Harris, CJ Burns, PM Jones
Journal of Molecular Endocrinology, 1999jme.bioscientifica.com
The role (s) played by protein tyrosine kinases (PTKs) in the regulation of insulin secretion
from pancreatic β cells is not clear. We have examined the effects of glucose, the major
physiological insulin secretagogue, on the tyrosine phosphorylation state of islet proteins,
and assessed β cell insulin secretory responses in the presence of PTK inhibitors. Under
basal conditions islets contained many proteins phosphorylated on tyrosine residues, and
glucose (20 mM; 5–15 min) was without demonstrable effect on the pattern of tyrosine …
Abstract
The role (s) played by protein tyrosine kinases (PTKs) in the regulation of insulin secretion from pancreatic β cells is not clear. We have examined the effects of glucose, the major physiological insulin secretagogue, on the tyrosine phosphorylation state of islet proteins, and assessed β cell insulin secretory responses in the presence of PTK inhibitors. Under basal conditions islets contained many proteins phosphorylated on tyrosine residues, and glucose (20 mM; 5–15 min) was without demonstrable effect on the pattern of tyrosine phosphorylation, in either the absence or presence of the protein tyrosine phosphatase (PTP) inhibitor, sodium pervanadate (PV). PV alone (100 µM) increased tyrosine phosphorylation of several islet proteins. The PTK inhibitors genistein (GS) and tyrphostin A47 (TA47) inhibited islet tyrosine kinase activities and glucose-, 4α ketoisocaproic acid (KIC)-and sulphonylurea-stimulated insulin release, without affecting glucose metabolism. GS and TA47 also inhibited protein serine/threonine kinase activities to a limited extent, but had no effect on Ca2+, cyclic AMP-or phorbol myristate acetate (PMA)-induced insulin secretion from electrically permeabilised islets. These results suggest that PTK inhibitors exert their inhibitory effects on insulin secretion proximal to Ca2+ entry and it is proposed that they act at the site of the voltage-dependent Ca2+ channel which regulates Ca2+ influx into β cells following nutrient-and sulphonylurea-induced depolarisation.
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