Hormonal Regulations of Glucose-6-Phosphate Dehydrogenase and Lipogenesis in Primary Cultures of Rat Hepatocytes1
- 1 February 1982
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Biochemistry
- Vol. 91 (2) , 681-693
- https://doi.org/10.1093/oxfordjournals.jbchem.a133741
Abstract
In primary cultured monolayer hepatocytes of adult rats, insulin (1×10 −8 m) induced glucose-6-phosphate dehydrogenase [EC 1.1.1.49, G6PDH] several fold in 48 h. It also induced lipogenesis, measured as [l- 14 C]acetate incorporation in 2h, in these cells. Of the various lipids, triglycerides and phospholipids were induced markedly, while cholesterol and its esters were not induced. The increase of G6PDH and lipogenesis were parallel. Glucagon, dibutyryl cyclic AMP, triiodothyronine, dexa-methasone, epinephrine, isoproterenol, and dibutyryl cyclic GMP were also tested under similar conditions, but none of them caused significant induction of G6PDH or lipogenesis. Use of anti-G6PDH serum showed that induction of G6PDH by insulin was due to increase in the amount of enzyme protein. Insulin was found to increase the rate of synthesis of G6PDH about 3-fold. SDS-polyacrylamide gel electro-phoresis of the immunoprecipitable protein revealed that besides G6PDH another radioactive fraction (Mr 37,000) was increased by insulin. This suggests that complete synthesis of G6PDH protein is slowed down in primary cultured hepatocytes and that an apparent nascent peptide of the enzyme accumulates. Although on long-term treatment (48 h), glucagon and dibutyryl cyclic AMP had no effect on lipogenesis, when added with [ l4 C]acetate for 2 h they strongly inhibited lipogenesis. Significant inhibition of lipogenesis by short-term treatment with glucagon was seen even in cells with a high capacity for lipogenesis induced by long-term treatment with insulin. Insulin again stimulated lipogenesis in short-term treatment, but its effect was slight. It is concluded from these results that insulin exerts long-term stimulation of lipogenesis by inducing enzymes related to lipogenesis including G6PDH as well as causing slight stimulation by enhancing supply of substrate for lipogenesis. Glucagon seems to play a minor role in long-term control, but it causes short-term inhibition of lipogenesis.Keywords
This publication has 5 references indexed in Scilit:
- Induction of L-lysine-2-oxoglutarate reductase by glucagon and glucocorticoid in developing and adult rats in vivo and in vitro studiesBiochimica et Biophysica Acta (BBA) - General Subjects, 1980
- Regulation of Glycogen Synthesis in Rat‐Hepatocyte Cultures by Glucose, Insulin and GlucocorticoidsEuropean Journal of Biochemistry, 1979
- Re-evaluation of lipogenesis from dietary glucose carbon in liver and carcass of mice.Journal of Lipid Research, 1978
- Coordinate regulation of acetyl coenzyme A carboxylase and fatty acid synthetase in liver cells of the developing chick in vivo and in cultureArchives of Biochemistry and Biophysics, 1978
- The Effect of Insulin on Enzyme Adaptations to Diets and HormonesJournal of Biological Chemistry, 1966