AMYLIN IMPAIRMENT OF INSULIN EFFECTS ON GLYCOGEN-SYNTHESIS AND PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE-EXPRESSION IN RAT PRIMARY CULTURED-HEPATOCYTES

The ability of amylin to impair hepatic insulin action is controversia l. We have found that the effect of amylin in primary cultured hepatoc ytes is strongly dependent on the culture conditions. Only in hepatocy tes preincubated in the presence of fetal serum did amylin, al concent rations ranging from 1 to 100 nM, reduce insulin-stimulated glycogen s ynthesis rate and glycogen accumulation without showing direct effects . Neither basal glycogen synthase nor glycogen phosphorylase activity was modified by amylin treatment. Nevertheless, amylin (100 nM) blocke d the activation of glycogen synthase by insulin. Amylin also proved c apable of opposing the reduction in the expression of the phosphoenolp yruvate carboxykinase (PEPCK) gene induced by insulin, whereas the bas al mRNA level of PEPCK was unaffected by amylin treatment. Thus, these results show that, in cultured rat hepatocytes, amylin is indeed able to interfere with insulin regulation of glycogenesis and PEPCK gene e xpression, favouring the hypothesis that amylin may modulate liver sen sitivity to insulin.