TY - JOUR
T1 - Mechanism of insulin-stimulated electrogenic sodium transport
AU - Rodriguez-Commes, Jose
AU - Isales, Carlos
AU - Kalghati, Leena
AU - Gasalla-Herraiz, Jose
AU - Hayslett, John P.
N1 - Funding Information:
This study was supported by the National Institute of Health, DK 18061. Drs. Rodriguez-Commes and Gasalla-Herraiz were supported by a grant from Fondo de Investigacion Sanitaria de Ia Seguridad Social of Spain (FISS, BAE 9015369 and BAE 92-5642). Dr. Isales was supported by a Physician-Scientist award (DK-19813). The authors are indebted to Larry Macala for technical assistance, and to M. Pucci and M. Taragowski for preparation of the figures and manuscript.
PY - 1994/9
Y1 - 1994/9
N2 - Studies were performed to determine the signal transduction mechanism involved in the onset of insulin stimulated electrogenic sodium transport (Ieq) in cultured A6 cells. Insulin stimulated Ieq at a threshold concentration of one nM and a half-maximum concentration of approximately 3 nM. The onset of action occurred within 10 seconds and the increase in Ieq was augmented by pretreatment with aldosterone, similar to the action of vasopressin. Insulin stimulated an increase in Ca(i)2+ in a dose-dependent manner that involved release from intracellular stores. Hormone stimulated Ieq was dependent on increases in Ca(i)2+ because pretreatment with 5, 5' dimethyl BAPTA/AM blocked the increase in sodium transport. Further studies with dihydroxyclorpromazine, trifluoperazine and genistein, inhibitors of PKC, Ca(i)2+ dependent, calmodulin dependent kinases and tyrosine kinase, respectively, suggested that the action of insulin was dependent on activation of these kinases. In contrast, insulin stimulated Ieq was independent of changes in cAMP, because insulin did not increase the accumulation of cAMP, and inhibition of adenylate cyclase with 2', 5' dideoxyadenosine did not affect transport. These results suggest that insulin, as previously shown for aldosterone, activates apical membrane amiloride sensitive sodium channels by a calcium-dependent second messenger system.
AB - Studies were performed to determine the signal transduction mechanism involved in the onset of insulin stimulated electrogenic sodium transport (Ieq) in cultured A6 cells. Insulin stimulated Ieq at a threshold concentration of one nM and a half-maximum concentration of approximately 3 nM. The onset of action occurred within 10 seconds and the increase in Ieq was augmented by pretreatment with aldosterone, similar to the action of vasopressin. Insulin stimulated an increase in Ca(i)2+ in a dose-dependent manner that involved release from intracellular stores. Hormone stimulated Ieq was dependent on increases in Ca(i)2+ because pretreatment with 5, 5' dimethyl BAPTA/AM blocked the increase in sodium transport. Further studies with dihydroxyclorpromazine, trifluoperazine and genistein, inhibitors of PKC, Ca(i)2+ dependent, calmodulin dependent kinases and tyrosine kinase, respectively, suggested that the action of insulin was dependent on activation of these kinases. In contrast, insulin stimulated Ieq was independent of changes in cAMP, because insulin did not increase the accumulation of cAMP, and inhibition of adenylate cyclase with 2', 5' dideoxyadenosine did not affect transport. These results suggest that insulin, as previously shown for aldosterone, activates apical membrane amiloride sensitive sodium channels by a calcium-dependent second messenger system.
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U2 - 10.1038/ki.1994.319
DO - 10.1038/ki.1994.319
M3 - Article
C2 - 7996787
AN - SCOPUS:0027963379
SN - 0085-2538
VL - 46
SP - 666
EP - 674
JO - Kidney International
JF - Kidney International
IS - 3
ER -