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Secretory processes,carbohydrate and lipid metabolism in isolated mouse hepatocytes: Aspects of regulation by glucagon and insulin
Authors:P Müller  A Singh  L Orci  B Jeanrenaud
Institution:Laboratoires de Recherches Médicales adn Institut d''Histologie et d''Embryologie, Geneva University Medical School, Geneva, Switzerland
Abstract:The procedure of Berry and Friend for isolation of inntact hepatocytes has been adapted to mouse livers. The ultrastructure of these cells was satisfactorily preserved. Isolated mouse hepatocytes secreted proteins and triacyglycerols. These secretory processes were inhibited by colchicine, indicating a likely involvement of the microtubular system for their normal occurence. Ultracentrifugation of medium incubated with hepatocytes, followed by electrophoresis and electron microscopic examination of the floating fraction (density < 1.006) allowed to conclude that secreted triacyglycerols were very low density lipoproteins. Glycogenolysis and lipogenesis were stimulated or inhibited, respectively, by low concenrations of glucagon (10?10 M). Other metabolic parameters were influenced by the hormone but were less sensitive to its action. Inhibition of lipogenesis by glucagon was associated with a decrease in acetyl CoA carboxylase activity. This increases does not appear to be related to intracellular fatty acyl-CoA accumulation secondary to hepatic lipase activation by the hormone. Insulin was effective alone or counteracted glucagon effects on lipogenesis or glycogenolysis only when exposure of cells to collagenase was held minimal. This suggests that, during isolation of hepatocytes, insulin receptors may, for unknown reasons, be more fragile than those of glucagon.
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