Insulin induces Ca2+ influx into isolated rat hepatocyte couplets

Benzeroual, K.; van de Werve, G.; Meloche, S.; Mathé, L.; Romanelli, A.; Haddad, P.

American Journal of Physiology 272(6 Pt 1): G1425-G1432

1997


ISSN/ISBN: 0002-9513
PMID: 9227478
Accession: 008886808

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Abstract
Isolated rat hepatocyte couplets were used to study the direct effect of insulin on intracellular Ca-2+ homeostasis. Insulin induced a dose-dependent increase in hepatocellular Ca-2+ that was gradual, generally monophasic, and reversible. Chelation of extracellular Ca-2+ abolished the insulin-induced Ca-2+ response, and this suppression was not related to an effect on insulin binding, as indicated by displacement studies. We thus tested the effect of several Ca-2+ channel inhibitors on insulin-induced Ca-2+ influx. Verapamil at 20 or 200 mu-M was without effect, whereas 500 mu-M nickel and 50 mu-M gadolinium strongly inhibited insulin-induced Ca-2+ entry. Finally, we tested whether insulin-induced Ca-2+ movements were implicated in the stimulation of mitogen-activated protein kinase (MAPK) activity, which we measured with the use of an immune-complex assay. Verapamil was without effect on the insulin-dependent stimulation of p44-mapk activity, whereas addition of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, nickel, or gadolinium strongly inhibited the effect of the peptide hormone. Our results indicate that insulin triggers Ca-2+ influx into hepatocytes, possibly through the opening of channels on the plasma membrane, and that this effect is important for insulin activation of MAPK.