Activity Of Liver Glycogen Synthetase Research Articles

Effect of cyclosporin A on carbohydrate metabolism in the rat.

Liver and kidney carbohydrate metabolism was investigated in rats treated with daily doses of 15 mg/kg body weight cyclosporin A (CyA) for 2 and 8 weeks or of 50 mg/kg body weight CyA for 2 weeks. The higher dosage caused significantly reduced liver glycogen and liver glycogen synthetase activity (of both active I-form and total enzyme activity), whereas the activity of the glycogen-degrading enzyme phosphorylase (active a-form and total activity) remained unchanged. Plasma glucose and glucagon levels, as well as blood ketone bodies of these animals, increased significantly and plasma insulin decreased. In contrast, kidney glycogen and glucose content were higher in rats treated with 50 mg CyA, probably due to enhanced ketone body utilization. Reduced liver glycogen synthetase activity was also found in rats treated with 15 mg CyA. Our data suggest that hypoinsulinemia, induced by CyA, might be a contributing factor to the hyperglycemia, which is mainly due to inhibition of liver glycogen synthesis.

Effect of cyclosporin A on carbohydrate metabolism in the rat

Abstract. Liver and kidney carbohydrate metabolism was investigated in rats treated with daily doses of 15 mg/kg body weight cyclosporin A (CyA) for 2 and 8 weeks or of 50 mg/kg body weight CyA for 2 weeks. The higher dosage caused significantly reduced liver glycogen and liver glycogen synthetase activity (of both active I-form and total enzyme activity), whereas the activity of the glycogen-degrading enzyme phosphorylase (active a-form and total activity) remained unchanged. Plasma glucose and glucagon levels, as well as blood ketone bodies of these animals, increased significantly and plasma insulin decreased. In contrast, kidney glycogen and glucose content were higher in rats treated with 50 mg CyA, probably due to enhanced ketone body utilization. Reduced liver glycogen synthetase activity was also found in rats treated with 15 mg CyA. Our data suggest that hypoinsulinemia, induced by CyA, might be a contributing factor to the hyperglycemia, which is mainly due to inhibition of liver glycogen synthesis.

Effects of high doses of leucine and ketoleucine on glycogen and protein metabolism in acute uremia

Binephrectomized rats treated with high doses of ketoleucine (0.5 g/rat per 20 hr) expired after about 45 hr. In contrast, survival time was 100% 60 hr after ureteral ligation. In comparison to animals receiving low-protein diets, addition of leucine to the diet almost doubled muscle and liver protein content whereas ketoleucine increased liver protein during the first 40 hr after operation about 1.5-fold. Skeletal muscle protein content was enhanced in the ureter-ligated rats with administration of ketoleucine. There was also about a 10-fold elevation in liver glycogen and total carbohydrate content between the 20th and 60th hr in binephrectomized rats fed leucine at 5-hr intervals. In skeletal muscle glycogen, there were no significant differences among the acutely uremic rats fed at 10-hr intervals low-protein diets alone or supplemented with leucine or ketoleucine. Leucine inhibits glycogenolysis by lowering phosphorylase alpha activity in muscle and liver, whereas ketoleucine enhances glycogenolysis in acute uremia. In rats supplemented with letoleucine, there is a progressive inactivation of glycogen synthetase I which occurs in parallel with increasing phosphorylase alpha activity. In binephrectomized rats receiving leucine supplements at 5-hr feeding intervals, the activity of liver glycogen synthetase I increases up to a maximum of 90% of total enzyme activity.

Changes-induced in liver and muscle glycogen and glycogen enzymes by 24-hour fasting in the rat.

Liver and muscle glycogen content, and the activities of glycogen synthetase, glycogen phosphorylase and alpha-amylase have been measured in fed and 24 hours fasted rats. Muscle and liver glycogen account for similar amounts of glycosyl residues liberated in this period of food deprivation. With fasting, liver glycogen synthetase activity decreases somewhat, increasing the I versus total ratio; the liver phosphorylase activity decreases considerably and amylases remain constant. In muscle, total synthetase remains constant with fasting, but the I versus total ratio decreases; phosphorylase activity decreases very considerably and alpha-amylase activity increases to almost thrice the values found in fed animals. These changes reflect a tendency towards conservation of glycogen primers with a preparation to increase glycogen synthesis when glucose would be available. In muscle also, the amylase increase in activity would be tentatively explained as a partial replacement of phosphorylase activity as a means of glucose mobilization from glycogen.

Hyperglycemia and Glycogen Storage in the Rabbit Fetal Liver

A 2-hour glucose infusion to pregnant rabbits resulted in fetal hyperglycemia. The question was studied whether this hyperglycemia would induce an increase in the concentration of glycogen in the fetal liver. The result depended upon the age of the fetus. In 24- or 25-day-old fetuses hyperglycemia did not increase the liver glycogen. On the contrary, on day 26, 27 and 28, the glycogen content in the liver was approximately twice as high as in controls. However, in fetuses which were decapitated on day 24 and studied on day 26, the maternal glucose infusion did not increase the glycogen stores. But in those fetuses decapitated on day 25 hyperglycemia provoked glycogen deposition. The activity of liver glycogen synthetase (active form alpha and total form a + b) increased between days 24 and 28 in control fetuses. Some increase of the alpha form already occurs between days 24 and 25. In fetuses decapitated on day 23, the alpha form was found almost as low on day 31 as it was on day 23. The incapacity of the liver of fetuses under 26 days of age or of those decapitated before day 25 to store glycogen under conditions of hyperglycemia probably results from a low glycogen synthetase activity.

Utilization of adenosine as a tool in studies on the regulation of liver glycogen biosynthesis

An eightfold increase in the active form of liver glycogen synthetase activity was detected in normal rats 1 hr after the intraperitoneal injection of adenosine. Such an increase is the highest yet observed after the administration of a specific hormone or compound. However, no change was detected in the total quantity of a plus b forms of the enzyme present in the liver. Previous administration of actinomycin or cycloheximide prevented increases in the active form of glycogen synthetase activity ordinarily provoked by the injection of the nucleoside. The addition of adenosine to rat liver homogenates did not cause a change in the active or total glycogen synthetase activity as compared to the control. The effect of adenosine was not mediated by insulin sincein diabetic rats the injection of the nucleoside was also followed by an increase in the active form of liver glycogen synthetase activity. Variation in the levels of blood glucose and serum inorganic phosphate and changes in the levels of inorganic phosphate in liver cells were also observed after adenosine administration. The maximum changes preceded the increase in the active form of hepatic glycogen synthetase in vivo. It is postulated that in the liver the synthetase phosphatase responsible for the conversion of the b into the a form of glycogen synthetase is the important point of regulation of glycogen biosynthesis.

Regulation of glycogen metabolism in liver by the autonomic nervous system: V. Activation of glycogen synthetase by vagal stimulation

1. 1. Electrical stimulation of the vagus nerve of rabbits caused a marked increase in the activity of liver glycogen synthetase (UDPG:α-1,4-glucan α-4-glucosyltransferase, EC 2.4.1.11). Stimulation of the splanchnic nerve resulted in a decrease in enzymic activity. 2. 2. On vagal stimulation the glycogen synthetase activity increased to nearly the maximal level within 10 min, and its change was closely correlated with the time course of decrease in the UDPG and Glc-6- P levels in the liver. 3. 3. Increase in enzymic activity on vagal stimulation is not due to a change in the total activity of the enzyme, but appears to be due to transformation of the enzyme to a form with higher affinities for UDPG and Glc-6- P. Vagal stimulation for 10 min lowered the apparent K m for UDPG from 2.9 · 10 −3 to 4.8 · 10 −4 M (determined in the presence of a physiological concentration of Glc-6- P, without causing a significant change in v max. The apparent K a for Glc-6- P was also lowered from 7.1 · 10 −4 to 2.2 · 10 −4 M by vagal stimulation. These effects of vagal stimulation were not affected by removal of the pancreas. 4. 4. Splanchnic-nerve stimulation caused a slight increase in the apparent K m for UDPG of glycogen synthetase, without affecting the value of vmax. 5. 5. These results indicate that vagal stimulation results in activation of glycogen synthetase, whereas splanchnic-nerve stimulation causes inactivation of the enzyme. The possible mechanisms and physiological significance for the actions of these two autonomic nerves on the regulation of glycogen synthetase and glycogen metabolism in the liver are discussed.

Effect of acetylcholine on glycogen formation and the activity of glycogen synthetase in isolated, perfused rat liver.

THE effect of adrenaline on carbohydrate metabolism in liver has been intensively investigated 1–3. On the other hand, very little is known about the role of acetylcholine4. The observation of Shimazu5 on the increase of the activity of liver glycogen synthetase after vagal stimulation induced us to investigate the possible effect of acetylcholine on carbohydrate metabolism in the isolated perfused rat liver. Part of the present results was reported elsewhere6.

On the possibility of metabolite control of liver glycogen synthetase activity.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPossibility of metabolite control of liver glycogen synthetase activityAlvin H. GoldCite this: Biochemistry 1970, 9, 4, 946–952Publication Date (Print):February 1, 1970Publication History Published online1 May 2002Published inissue 1 February 1970https://doi.org/10.1021/bi00806a034RIGHTS & PERMISSIONSArticle Views24Altmetric-Citations53LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (694 KB) Get e-Alerts Get e-Alerts

The influence of inorganic phosphate, adenosine triphosphate and glucose 6-phosphate on the activity of liver glycogen synthetase.

The important activation of liver glycogen synthetase which occurs after a load of glucose or after the administration of glucocorticoids and which could be demonstrated by assaying the enzyme in a concentrated liver homogenate [1,2], is due to the conversion of an inactive or b form of the enzyme into another form called a, which is active under physiological conditions. This conversion is similar to that previously shown to occur in vitro by Segal and his coworkers [7,8]. The native or b form is prevalent in the untreated animal and has a low affinity for UDPG and for glucose 6‐phosphate; it is active only in the presence of glucose 6‐phosphate but this activity is cancelled by Pi, sulfate, sulfite and ATP. Consequently it remains inactive in the concentrated liver homogenate, which is rich in Pi, and also in vivo, due to the intracellular concentrations of Pi and ATP. Glycogen synthetase a has a high affinity for UDPG and for glucose 6‐phosphate; it is stabilized by phosphate, sulfate and sulfite as well as by glucose 6‐phosphate. It is inhibited by ATP but this inhibition is mostly overcome by physiological amounts of Pi. It is therefore fully active in a concentrated homogenate and in vivo. Magnesium ions have on both forms of the enzyme an effect which is similar to that of glucose 6‐phosphate.Glycogen synthetase a is conveniently measured in a diluted liver homogenate in the presence of 10 mM sulfate; the activities found in these conditions correlate with those measured in a concentrated homogenate and therefore with the rate of liver glycogen synthesis in vivo. in the cell, Pi appears to be the most important activator of the enzyme, whereas glucose 6‐phosphate has only a minor role.

Regulation of Liver Glycogen Synthetase Activity

Regulation of Liver Glycogen Synthetase Activity

An on-off mechanism for liver glycogen synthetase activity.

An on-off mechanism for liver glycogen synthetase activity.

The stimulation of glycogen synthesis and of glycogen synthetase in the liver by the administration of glucose.

The intravenous administration of glucose to the mouse stimulates 15–20 and up to 40‐fold the conversion of glucose to glycogen in the liver. This effect is observed in the normally fed as well as in the fasted animal and requires 5 min to reach its full development. At that time, the hepatic concentration of glucose 6‐phosphate and of UDPG is markedly lowered whereas the activity of glycogen synthetase, when measured in a concentrated liver homogenate, is greatly increased. The rate of glycogen synthesis is not correlated with the concentration of glucose in the liver but is highly significantly correlated with the activity of liver glycogen synthetase.

Glycogen synthetase activity in liver: regulation by the autonomic nerves.

Electrical stimulation of the vagus nerve in intact or pancreatectomized rabbits resulted in a marked increase, within 5 minutes of the onset of stimulation, in the total activity of liver glycogen synthetase. The effect was completely counteracted by simultaneous stimulation of the splanchnic nerve, although stimulation of the splanchnic nerve alone had little effect on the enzyme. Injection of insulin caused an increase in both the total activity of glycogen synthetase and the activity that was independent of glucose-6-phosphate. The response of the enzyme to vagal stimulation was much faster than to administration of insulin.

Time-dependent increase in rat liver glycogen synthetase activity in vitro

Incubation of glycogen synthetase preparations brings about marked increases in both glucose-6-P dependent and independent activities. The increase is preceded by a lag period whose duration is temperature-dependent. The “activation” is not reversible upon recooling. Major differences exist in kinetic properties of the “nonactivated” And “activated” forms in regard to the glycogen saturation curve and the ATP inhibitability.

Influence of age on liver glycogenesis in rats exposed to acceleration stress.

Overnight-fasted rats ranging in age from 8 to 104 days were stressed by centrifugation for 2.5 or 5.0 hr at 4.7 g. Liver glycogen, plasma corticosterone, liver glycogen synthetase and plasma glucose were determined in stressed rats as a function of age and compared to noncentrifuged control rats. Significant increases in liver glycogen deposition occurred in centrifuged rats 18 days or older but not in younger rats. The unresponsiveness of the younger rats was attributed to their limited ability to elaborate increased amounts of adrenal corticosterone during centrifugation. Liver glycogen synthetase was increased significantly by centrifugation in selected groups of the older animals. An increase in synthetase was not a necessary step in the observed increase in liver glycogenesis in centrifuged rats. Glucose or corticosterone, either alone or in combination, administered to normal unstressed rats had no significant effect on liver glycogen synthetase activity. (Endocrinology 78: 556, 1966)