engleski

Protein Kinase Cδ but not PKCα is Involved in Insulin-Induced Glucose Metabolism in Hepatocytes

The liver is the major insulin-responsible tissue for glucose regulation. One important mechanism in this phenomenon is insulin-induced glycogen synthesis. Studies in our laboratory have shown that Protein Kinase Cs delta (PKCδ) and alpha (α) have important roles in insulin-induced glucose transport in sceletal muscle, and that their expression and activity being regulated by insulin. Their importance in glucose regulation in liver cells is unclear. In this study we investigated the possibility that these isoform are involved in the mediation of insulin-induced glycogen synthesis in hepatocytes. Studies were done on rat hepatocytes in primary culture and on the AML-12 (Alpha Mouse Liver) cell line. Insulin increased activity and tyrosine phosphorylation of PKCδ within 5 min. In contrast, activity and tyrosine phosphorylation of PKCα were not increased by insulin. PKCδ was constitutively associated with IR, and this was increased by insulin stimulation. Suppression of PKCδ expression by transfection with RNAi, or overexpression of kinase dead (Dominant Negative) PKCδ reduced both the insulin-induced activation of PKB/Akt and the phosphorilation of Glycogen Sinthase Kinase 3 (GSK3) and reduced significantly insulin-induced glucose uptake. In addition, treatment of primary rat hepatocytes with rottlerin abrogated insulin-induced increase in glycogen synthesis. Neither overexpression nor inhibition of PKCα appeared to alter activation of PKB, phosphorylation of GSK3 or glucose uptake in response to insulin. We conclided that PKCδ, but not PKCα, plays an essential role in insulin-induced glucose uptake and glycogenesis in hepatocytes.

PKC isoforms; PKCδ; PKCα; Insulin signaling; Glycogenesis; Hepatocytes

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