Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D

Figure 7

Effect of doxorubicin and inhibitors of sphingolipid turnover and phospholipase D activity on ceramide content and glucose metabolism stimulation by insulin in the isolated hepatocytes. (a) [¹⁴C]ceramide, (b) uptake of 2-D-[³H]glucose, (c) incorporation of D-[U ¹⁴C]glucose into glycogen. 1: cells treated with DMSO (control cells); 2: doxorubicin; 3: doxorubicin + total sphingolipid turnover inhibitors; 4: doxorubicin + total sphingolipid turnover inhibitors + halopemide (200 nM); 5: doxorubicin + total sphingolipid turnover inhibitors + halopemide (300 nM). Effect of insulin on phospholipase D activity and glucose metabolism in drug-pretreated hepatocytes was determined as described in the Methods. , doxorubicin versus control; , doxorubicin + drug versus doxorubicin; , insulin versus control.

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