Control of rat liver glycogen synthetase and phosphorylase activities by glucose

Glinsmann, Walter H.; Pauk, George L.; Hern, Eugene P.

doi:10.1016/0006-291x(70)90272-x

Cited by 108 publications

(47 citation statements)

References 16 publications

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“…As this effect has been obtained in animals made acutely diabetic by the administration of antiinsulin serum [23], it seems not to be mediated by insulin. In agreement with this conclusion, the activation of glycogen synthetase by a glucose load has been recently observed in perfused rat liver [24,25].…”

Section: The Rate Limiting Enzymes; Their Phosphorylation and Dephospsupporting

confidence: 68%

“…An increase in the concentration of glucose in vivo [26][27][28] or in the isolated perfused liver [24,25] initiates a slight decrease in the amount of active phosphorylase; this effect is much!less striking than that on glycogen synthetase. It is a usual finding that the activity of phosphorylase a measured in a fresh liver homogenate largely exceeds what would be expected from the actual rate of glycogenolysis.…”

Section: The Rate Limiting Enzymes; Their Phosphorylation and Dephospmentioning

confidence: 99%

“…It is poorly active in preparations obtained from fasted animals, but recovers its full activity if 0.5% glycogen is: added [6,55]. The enzyme is also inactive in liver extracts [56] and in perfused livers [25] obtained from fasted adrenalectomized rats, despite the fact that glycogen synthesis rapidly occurs in vivo upon refeeding of these animals [18,19].…”

Section: The Control Of Synthetase Phosphatase By Phosphorylasementioning

confidence: 99%

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The control of glycogen metabolism in the liver

1970

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Section: The Rate Limiting Enzymes; Their Phosphorylation and Dephospsupporting

confidence: 68%

Section: The Rate Limiting Enzymes; Their Phosphorylation and Dephospmentioning

confidence: 99%

Section: The Control Of Synthetase Phosphatase By Phosphorylasementioning

confidence: 99%

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The control of glycogen metabolism in the liver

1970

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“…Stimulation of glycogen synthesis and activation of glycogeia synthetase by insulin have previously been shown in perfused livers [1,2], but these effects have remained controversial due to several negative reports [20,21]. Wagle et al [3], however, using isolated hepatocytes reported recently that insulin directly controls glycogen synthesis in vivo and in vitro which was corroborated by an insulin stimulated enhancement of [ w -l a f ] -g l u c o s e incorporation into glycogen [4].…”

Section: Discussionmentioning

confidence: 99%

Effect of insulin on glycogen and protein synthesis in monolayer cultures of hepatocytes from normal and alloxan diabetic rats

et al. 1977

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Summary. The effects of insulin on net glycogen synthesis and amino acid incorporation into protein were studied in cultured hepatocytes from adult normal and alloxan diabetic rats. Insulin stimulated glycogen synthesis in monolayer cells throughout a four day culture period and enhanced leucine incorporation into protein more effectively in normal cells with high glycogen levels than in cultured diabetic cells. These differences correlate well with the observed cellular ultrastructures which were maintained much better in the presence of insulin. Restoration of the morphological changes of alloxan diabetic hepatocytes to normal liver cell structures can be observed at any time during the culture period by giving insulin continuously.Key words: Insulin, glycogen, amino acid, alloxan diabetes, cultured hepatocytes.It has been generally accepted that insulin plays an essential role in the regulation of carbohydrate and protein metabolism in liver tissue. The specific nature of its action at cellular level has been previously investigated in perfused liver [1,2] and in hepatocyte suspensions [3,4], but various attempts to obtain hepatocytes capable of efficient glycogen synthesis during a several day culture period have not been successful. Cultured hepatocytes have, however, become increasingly popular as a valuable system for investigating many liver biochemical runePresent address. Department of Biochemistry, University of Surrey, Gufldford, Surrey GU2 5XH, England 2 Pathologisches Instltut der Universitat Tfibmgen, D-7400 Ttibingen 9 tions in vitro [5,6]. We set out to develop a hepatocyte preparation capable of glycogen synthesis from normal gluconeogenic substrates. It was, therefore, of considerable interest to see if these cultured hepatocytes, especially from diabetic animals could synthesize cellular glycogen in the presence of insulin, and if amino acid incorporation into protein could be stimulated by the hormone even after several days in culture. In the present study we report the stimulatory effect of insulin on hepatic glycogen and protein synthesis and interrelate it with ultrastructural alterations in monolayer cultures of normal and diabetic rat hepatocytes. Materials and Methods Isolation and Cultivation of HepatocytesMale Sprague-Dawley rats weighing 100-150g were used throughout. All rats were kept on a standard laboratory diet (Altromin | and tap water ad libitum. The animals had easy access to food from a dish placed on the floor. This procedure was recently reported to enhance significantly liver glycogen content [7]. Hepatocytes were isolated by a modified method of collagenase/hyaluronidase (50 and 100 rag, respectively, per 100 ml Hank's solution) digestion of liver slices, which is especially suitable for harvesting a large number of viable cells from small liver pieces, e.g. biopsy samples [8]. The total cell yield and the viability index (percentage of viable cells) were calculated in duplicate with a haemocytometer; viability was based on the ability of cells to exclude the dye, tryp...

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“…The stimulatory effect of insulin on glycogen synthesis in various tissues was among the first metabolic actions of this hormone studied in detail [1,2]. Insulin stimulated the activity of the liver glycogen synthase, the rate-limiting enzyme in the pathway from G-6-P to glycogen, and inhibited the glycogen phosphorylase activity [3][4][5][6][7][8][9][10][11]. The activity of glycogen synthase is partially regulated by its state of phosphorylation [1,2,12,13].…”

mentioning

confidence: 99%

Insulin Stimulates Protein Synthesis of Glycogen Synthase in Rat Hepatoma H4 Cells Associated with Acceleration of Translation Rate.

et al. 1996

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Abstract.To assess the regulatory mechanism of insulin action on the biosynthesis of glycogen synthase under long-term control, we investigated post-transcriptional and post-translational regulation by insulin of glycogen synthase in rat hepatoma H4 cells. Glycogen synthase protein gradually increased in response to insulin and peaked at 6 h during a 24-h insulin incubation (185% of the control), corresponding with the second peak of glycogen synthase activation measured by the activity ratio (low glucose 6-P/high glucose 6-P). The effect of insulin on synthesis of glycogen synthase protein was assessed by measuring the incorporation of [35S]-methionine into the enzyme protein during a 6-h insulin incubation. The amount of [35S]-methionine incorporation into glycogen synthase was increased in response to insulin with time, and peaked at 4 h (250% of the control). The degradation of glycogen synthase examined by measuring the rate of reduction of [35S]-methionine for 6 h after the tracer incubation for 12 h was not affected by insulin.The results indicate that (a) insulin induces glycogen synthase activity by accumulating the enzyme protein due to stimulation of protein synthesis rather than inhibition of protein degradation and (b) insulin-reduced stability of glycogen synthase mRNA is caused by acceleration of the translation rate.

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Control of rat liver glycogen synthetase and phosphorylase activities by glucose

Cited by 108 publications

References 16 publications

The control of glycogen metabolism in the liver

The control of glycogen metabolism in the liver

Effect of insulin on glycogen and protein synthesis in monolayer cultures of hepatocytes from normal and alloxan diabetic rats

Insulin Stimulates Protein Synthesis of Glycogen Synthase in Rat Hepatoma H4 Cells Associated with Acceleration of Translation Rate.

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