scholarly journals Swelling of rat hepatocytes activates acetyl-CoA carboxylase in parallel to glycogen synthase

1991 ◽  
Vol 278 (3) ◽  
pp. 887-890 ◽  
Author(s):  
A Baquet ◽  
L Maisin ◽  
L Hue
Keyword(s):  
Amino Acids ◽  
Glycogen Synthase ◽  
Rat Hepatocytes ◽  
Cell Swelling ◽  
Common Mechanism ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Parallel Activation

Incubation of hepatocytes in conditions known to increase their volume, i.e. with amino acids or in hypo-osmotic media, resulted in the parallel activation of glycogen synthase and acetyl-CoA carboxylase. The activation of both enzymes by glutamine was antagonized by the addition of raffinose to prevent cell swelling, or by glucagon and microcystin. The findings are consistent with the involvement of a common mechanism for the activation of the two enzymes.

Fatty acid and amino acid modulation of glucose cycling in isolated rat hepatocytes

2001 ◽  
Vol 358 (3) ◽  
pp. 665-671 ◽  
Author(s):  
Lori A. GUSTAFSON ◽  
Mies NEEFT ◽  
Dirk-Jan REIJNGOUD ◽  
Folkert KUIPERS ◽  
Hans P. SAUERWEIN ◽  
...  
Keyword(s):  
Amino Acids ◽  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Lactate Production ◽  
Rat Hepatocytes ◽  
Glycolytic Flux ◽  
Isolated Rat Hepatocytes ◽  
Glycogen Accumulation ◽  
Glycogen Deposition ◽  
Intracellular Glucose

We studied the influence of glucose/glucose 6-phosphate cycling on glycogen deposition from glucose in fasted-rat hepatocytes using S4048 and CP320626, specific inhibitors of glucose-6-phosphate translocase and glycogen phosphorylase respectively. The effect of amino acids and oleate was also examined. The following observations were made: (1) with glucose alone, net glycogen production was low. Inhibition of glucose-6-phosphate translocase increased intracellular glucose 6-phosphate (3-fold), glycogen accumulation (5-fold) without change in active (dephosphorylated) glycogen synthase (GSa) activity, and lactate production (4-fold). With both glucose 6-phosphate translocase and glycogen phosphorylase inhibited, glycogen deposition increased 8-fold and approached reported in vivo rates of glycogen deposition during the fasted → fed transition. Addition of a physiological mixture of amino acids in the presence of glucose increased glycogen accumulation (4-fold) through activation of GS and inhibition of glucose-6-phosphatase flux. Addition of oleate with glucose present decreased glycolytic flux and increased the flux through glucose 6-phosphatase with no change in glycogen deposition. With glucose 6-phosphate translocase inhibited by S4048, oleate increased intracellular glucose 6-phosphate (3-fold) and net glycogen production (1.5-fold), without a major change in GSa activity. It is concluded that glucose cycling in hepatocytes prevents the net accumulation of glycogen from glucose. Amino acids activate GS and inhibit flux through glucose-6-phosphatase, while oleate inhibits glycolysis and stimulates glucose-6-phosphatase flux. Variation in glucose 6-phosphate does not always result in activity changes of GSa. Activation of glucose 6-phosphatase flux by fatty acids may contribute to the increased hepatic glucose production as seen in Type 2 diabetes.

scholarly journals Inhibition of autophagic proteolysis by inhibitors of phosphoinositide 3-kinase can interfere with the regulation of glycogen synthesis in isolated hepatocytes

2002 ◽  
Vol 368 (3) ◽  
pp. 827-833 ◽  
Author(s):  
Peter F. DUBBELHUIS ◽  
Daphne A. VAN SLUIJTERS ◽  
Edward F.C. BLOMMAART ◽  
Lori A. GUSTAFSON ◽  
George M. VAN WOERKOM ◽  
...  
Keyword(s):  
Amino Acids ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Proteinase Inhibitors ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Regulatory Volume Decrease ◽  
Isolated Hepatocytes ◽  
Cell Swelling ◽  
Phosphoinositide 3 Kinase

Amino acid-induced cell swelling stimulates conversion of glucose into glycogen in isolated hepatocytes. Activation of glycogen synthase (GS) phosphatase, caused by the fall in intracellular chloride accompanying regulatory volume decrease, and activation of phosphoinositide 3-kinase (PI 3-kinase), induced by cell swelling, have been proposed as underlying mechanisms. Because PI 3-kinase controls autophagic proteolysis, we examined the possibility that PI 3-kinase inhibitors interfere with glycogen production due to their anti-proteolytic action. The PI 3-kinase inhibitor wortmannin inhibited endogenous proteolysis, the production of glycogen from glucose and the activity of active (dephosphorylated) GS (GSa) in the absence of added amino acids. The stimulation by amino acids of glycogen production and of GSa was only slightly affected by wortmannin. These effects of wortmannin could be mimicked by proteinase inhibitors. A combination of leucine, phenylalanine and tyrosine, which we showed previously to stimulate PI 3-kinase-dependent phosphorylation of ribosomal protein S6, did not stimulate glycogen production from glucose. In contrast with wortmannin, LY294002, another PI 3-kinase inhibitor, strongly inhibited both glycogen synthesis and GSa activity, irrespective of the presence of amino acids. Inhibition of glycogen synthesis by LY294002 could be ascribed in part to increased glycogenolysis and glycolysis. It is concluded that, in hepatocytes, activation of PI 3-kinase may not be responsible for the stimulation of glycogen synthesis by amino acids; LY294002 inhibits glycogen synthesis and stimulates glycogen breakdown by a mechanism that is unrelated to its action as an inhibitor of PI 3-kinase.

scholarly journals Glucose Regulation of the Acetyl-CoA Carboxylase Promoter PI in Rat Hepatocytes

2001 ◽  
Vol 276 (19) ◽  
pp. 16033-16039 ◽  
Author(s):  
Brennon L. O'Callaghan ◽  
Seung-Hoi Koo ◽  
Yue Wu ◽  
Hedley C. Freake ◽  
Howard C. Towle
Keyword(s):  
Rat Hepatocytes ◽  
Glucose Regulation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa

scholarly journals Role of protein synthesis in the carbohydrate-induced changes in the activities of acetyl-CoA carboxylase and hydroxymethylglutaryl-CoA reductase in cultured rat hepatocytes

1985 ◽  
Vol 227 (3) ◽  
pp. 939-947 ◽  
Author(s):  
J T Spence ◽  
A P Koudelka ◽  
J C L Tseng-Crank
Keyword(s):  
Protein Synthesis ◽  
Culture Medium ◽  
Relative Rate ◽  
Rat Hepatocytes ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Hmg Coa Reductase ◽  
Translatable Mrna ◽  
Coa Reductase

Changes in the activities of acetyl-CoA carboxylase and HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase were studied in primary cultures of adult-rat hepatocytes after exposure of the cells to insulin and/or carbohydrates. To determine the contribution of protein synthesis to changes in enzyme activity, the relative rate of synthesis of each enzyme was measured and the amount of translatable mRNA coding for the enzymes was determined by translation in vitro and immunoprecipitation. Addition of insulin to the culture medium increased the activities of acetyl-CoA carboxylase and HMG-CoA reductase by approx. 4- and 3-fold respectively. Although similar increases in the relative rate of synthesis of each protein and template activity were noted, initial increases in the activity of each enzyme occurred before any changes in protein synthesis were observed, suggesting the involvement of post-translational modification of enzyme activity in addition to changes in protein synthesis. The addition of fructose to the culture medium, in the absence of insulin, increased the activity of the carboxylase and the reductase approx. 3-fold, similar to the effects of insulin. However, the effect of fructose was to increase the rate of synthesis and the amount of translatable mRNA coding for acetyl-CoA carboxylase, whereas the increase in the activity of HMG-CoA reductase was not accompanied by any changes in the rate of synthesis or template activity. The effects of fructose could not be mimicked by glucose unless insulin was also present in the culture medium. Similar to observations in vitro, the injection of insulin or the feeding of a high-fructose diet to rats made diabetic by the injection of streptozotocin produced an increase in the activities of acetyl-CoA carboxylase and HMG-CoA reductase, and only the increase in the activity of the carboxylase was accompanied by an increase in the amount of translatable mRNA coding for the enzyme. The results are discussed in terms of the effects of fructose on the synthesis of enzymes involved in lipogenesis.

scholarly journals Mechanism of activation of liver acetyl-CoA carboxylase by cell swelling

1993 ◽  
Vol 217 (3) ◽  
pp. 1083-1089 ◽  
Author(s):  
Arnaud BAQUET ◽  
Vinciane GAUSSIN ◽  
Mathieu BOLLEN ◽  
Willy STALMANS ◽  
Louis HUE
Keyword(s):  
Cell Swelling ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa

scholarly journals Multiple signalling pathways involved in the stimulation of fatty acid and glycogen synthesis by insulin in rat epididymal fat cells

1995 ◽  
Vol 311 (2) ◽  
pp. 595-601 ◽  
Author(s):  
S K Moule ◽  
N J Edgell ◽  
G I Welsh ◽  
T A Diggle ◽  
E J Foulstone ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Pyruvate Dehydrogenase ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Signalling Pathways ◽  
Fat Cells ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Stimulation Of

We have investigated the signalling pathways involved in the stimulation of glycogen and fatty acid synthesis by insulin in rat fat cells using wortmannin, an inhibitor of phosphatidylinositol 3-kinase, and rapamycin, which blocks activation of p70 ribosomal S6 protein kinase (p70S6K). Insulin produced a decrease in the activity of glycogen synthase kinase-3 which is likely to be important in the observed stimulation of glycogen synthase. Both of these actions were found to be sensitive to inhibition by wortmannin. Activation of three processes is involved in the stimulation of fatty acid synthesis from glucose by insulin, namely glucose uptake, acetyl-CoA carboxylase and pyruvate dehydrogenase. Whereas wortmannin largely abolished the effects of insulin on glucose utilization and acetyl-CoA carboxylase activity, it was without effect on the stimulation of pyruvate dehydrogenase. Although epidermal growth factor stimulated mitogen-activated protein kinase to a greater extent than insulin, it was unable to mimic the effect of insulin on glycogen synthase, glycogen synthase kinase-3, glucose utilization, acetyl-CoA carboxylase or pyruvate dehydrogenase. Rapamycin also failed to have any appreciable effect on stimulation of these parameters by insulin, although it did block the effect of insulin on p70S6K. We conclude that the activity of phosphatidylinositol 3-kinase is required for the effects of insulin on glycogen synthesis, glucose uptake and acetyl-Co-AN carboxylase, but is not involved in signalling to pyruvate dehydrogenase. Activation of mitogen-activated protein kinase or p70S6K, however, does not appear to be sufficient to bring about the stimulation of fatty acid or glycogen synthesis. Altogether is seems likely that at least four distinct signalling pathways are involved in the effects of insulin on rat fat cells.

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