Insulin effects are mediated by multiple integrated signals generated by the insulin receptor. Fibroblasts, as most of mammalian cells, are a target of insulin action and are important actors in the vascular pathogenesis of hyperinsulinemia. A role for calcium-calmodulin-dependent kinases ( CaMK) in insulin signaling has been proposed but has been under investigated. We investigated the role of the CaMK isoform II in insulin signaling in human fibroblasts. A rapid and transient increase of intracellular calcium concentration was induced by insulin stimulation, followed by increase of CaMKII activity, via L type calcium channels. Concomitantly, insulin stimulation induced Raf-1 and ERK activation, followed by thymidine uptake. Inhibition of CaMKII abrogated the insulin-induced Raf-1 and ERK activation, resulting also in the inhibition of thymidine incorporation. These results demonstrate that in fibroblasts, insulin-activated CaMKII is necessary, together with Raf-1, for ERK activation and cell proliferation. This represents a novel mechanism in the control of insulin signals leading to fibroblast proliferation, as well as a putative site for pharmacological intervention.

Insulin stimulates fibroblast proliferation through calcium-calmodulin-dependent kinase II / Monaco, Sara; Illario, Maddalena; Rusciano, M. R.; Gragnaniello, G.; DI SPIGNA, Gaetano; Leggiero, Eleonora; Pastore, Lucio; Fenzi, Gianfranco; Rossi, Guido; Vitale, Mario. - In: CELL CYCLE. - ISSN 1538-4101. - STAMPA. - 8:13(2009), pp. 2024-2030.

Insulin stimulates fibroblast proliferation through calcium-calmodulin-dependent kinase II

MONACO, SARA;ILLARIO, MADDALENA;DI SPIGNA, GAETANO;LEGGIERO, ELEONORA;PASTORE, LUCIO;FENZI, GIANFRANCO;ROSSI, GUIDO;VITALE, MARIO
2009

Abstract

Insulin effects are mediated by multiple integrated signals generated by the insulin receptor. Fibroblasts, as most of mammalian cells, are a target of insulin action and are important actors in the vascular pathogenesis of hyperinsulinemia. A role for calcium-calmodulin-dependent kinases ( CaMK) in insulin signaling has been proposed but has been under investigated. We investigated the role of the CaMK isoform II in insulin signaling in human fibroblasts. A rapid and transient increase of intracellular calcium concentration was induced by insulin stimulation, followed by increase of CaMKII activity, via L type calcium channels. Concomitantly, insulin stimulation induced Raf-1 and ERK activation, followed by thymidine uptake. Inhibition of CaMKII abrogated the insulin-induced Raf-1 and ERK activation, resulting also in the inhibition of thymidine incorporation. These results demonstrate that in fibroblasts, insulin-activated CaMKII is necessary, together with Raf-1, for ERK activation and cell proliferation. This represents a novel mechanism in the control of insulin signals leading to fibroblast proliferation, as well as a putative site for pharmacological intervention.
2009
Insulin stimulates fibroblast proliferation through calcium-calmodulin-dependent kinase II / Monaco, Sara; Illario, Maddalena; Rusciano, M. R.; Gragnaniello, G.; DI SPIGNA, Gaetano; Leggiero, Eleonora; Pastore, Lucio; Fenzi, Gianfranco; Rossi, Guido; Vitale, Mario. - In: CELL CYCLE. - ISSN 1538-4101. - STAMPA. - 8:13(2009), pp. 2024-2030.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/357960
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