TY - JOUR
T1 - Novel effect of insulin
T2 - Insulin-stimulated Na+ transport is mediated by hydrolysis of phosphoinositides
AU - Isales, Carlos
AU - MacAla, Lawrence J.
AU - Rodriguez-Commes, Jose
AU - Gasalla-Herraiz, Jose
AU - Hayslett, John P.
N1 - Funding Information:
This study was supported by the National Institutes of Health Grants DK18061 and DK19813, the Juvenile Diabetes Foundation, and the Fondo de Investigacion Sanitaria de la Seguridad Social of Spain (FISS BAE 9015369 and BAE 92-5642).
PY - 1997/2/3
Y1 - 1997/2/3
N2 - Previous studies showed that insulin stimulation of electrogenic Na+ transport in renal epithelial cells is mediated by a calcium-dependent signal transduction mechanism. The present study was performed to determine whether the insulin-induced increase in intracellular Ca2+ (Ca(i)2+) was mediated by hydrolysis of phosphatidylinositol and release of inositol trisphosphate. Experiments were conducted with cultured A6 cells, derived from Xenopus laevis, grown on permeable supports. Addition of insulin resulted in 2 to 3 fold increases in inositol trisphosphate and a 50% increase in 1,2 diacylglycerol within 10s, which corresponded to the time-course, previously reported, of insulin stimulated increases in Na+ transport and Ca(i)2+. Further studies showed that aldosterone, previously shown to stimulate an increase in 1,4,5-inositol trisphosphate at onset of the rise in Na+ transport, also increased DAG levels during the initial phase of stimulation of Na+ transport. These studies provide the first evidence that a biological response induced by insulin is mediated by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) which results in two products, inositol trisphosphate which causes the release of Ca2+ from intracellular stores and 1,2 diacylglycerol. In addition this study provides further support for the proposal that a common signal transduction mechanism mediates electrogenic Na+ transport by multiple agonists.
AB - Previous studies showed that insulin stimulation of electrogenic Na+ transport in renal epithelial cells is mediated by a calcium-dependent signal transduction mechanism. The present study was performed to determine whether the insulin-induced increase in intracellular Ca2+ (Ca(i)2+) was mediated by hydrolysis of phosphatidylinositol and release of inositol trisphosphate. Experiments were conducted with cultured A6 cells, derived from Xenopus laevis, grown on permeable supports. Addition of insulin resulted in 2 to 3 fold increases in inositol trisphosphate and a 50% increase in 1,2 diacylglycerol within 10s, which corresponded to the time-course, previously reported, of insulin stimulated increases in Na+ transport and Ca(i)2+. Further studies showed that aldosterone, previously shown to stimulate an increase in 1,4,5-inositol trisphosphate at onset of the rise in Na+ transport, also increased DAG levels during the initial phase of stimulation of Na+ transport. These studies provide the first evidence that a biological response induced by insulin is mediated by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) which results in two products, inositol trisphosphate which causes the release of Ca2+ from intracellular stores and 1,2 diacylglycerol. In addition this study provides further support for the proposal that a common signal transduction mechanism mediates electrogenic Na+ transport by multiple agonists.
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U2 - 10.1006/bbrc.1997.6063
DO - 10.1006/bbrc.1997.6063
M3 - Article
C2 - 9070240
AN - SCOPUS:0031550558
SN - 0006-291X
VL - 231
SP - 156
EP - 159
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -