Studies on the effects of insulin and acetylcholine on activation of glycogen synthase and on glycogenesis in hepatocytes isolated from normal fed rats

Akpan, Jones O.; Gardner, Russell; Wagle, S.R.

doi:10.1016/0006-291x(74)90556-7

Cited by 59 publications

(21 citation statements)

References 12 publications

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“…The most likely explanation thus far appears to involve the central nervous system. Reports from several different investigators (45)(46)(47)(48)(49)(50)(51)(52)(53) support the idea that the parasympathetic nervous system may be playing an important role in this phenomenon. In addition, in a recent report from this laboratory (54), it was noted that a nearly complete denervation of the liver caused the loss ofthe effects ofintraportal glucose delivery on NHGU in the dog, suggesting that the effects of intraportal glucose delivery are neurally mediated.…”

Section: Discussionmentioning

confidence: 88%

Intraportal glucose delivery alters the relationship between net hepatic glucose uptake and the insulin concentration.

Myers¹,

McGuinness²,

Neal³

et al. 1991

J. Clin. Invest.

127

116

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To examine the relationship between net hepatic glucose uptake (NHGU) and the insulin level and to determine the effects of portal glucose delivery on that relationship, NHGU was evaluated at three different insulin levels in seven 42-h-fasted, conscious dogs during peripheral glucose delivery and during a combination of peripheral and portal glucose delivery. During peripheral glucose delivery, at arterial blood glucose levels of -175 mg/dl and insulin levels reaching the liver of 51±2, 92±6, and 191±6 ,uU/ml, respectively, NHGUs were 0.55±0.30, 1.52±0.44, and 3.04±0.79 mg/kg per min, respectively. At hepatic glucose loads comparable to those achieved during peripheral glucose delivery and inflowing insulin levels of 50±4, 96±5, and 170±8 gU per ml, respectively, NHGUs were 1.96±0.48, 3.67±0.68, and 5.52±0.92 mg/kg per min when a portion of the glucose load was delivered directly into the portal vein. The results of these studies thus indicate that net hepatic glucose uptake is dependent on both the plasma insulin level and the route of glucose delivery and that under physiological conditions the "portal" signal is at least as important as insulin in the determination of net hepatic glucose uptake. (J. Clin. Invest. 1991.87:930-939.)

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Section: Discussionmentioning

confidence: 88%

Intraportal glucose delivery alters the relationship between net hepatic glucose uptake and the insulin concentration.

Myers¹,

McGuinness²,

Neal³

et al. 1991

J. Clin. Invest.

127

116

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“…4 In other tissues, such as skeletal muscle, the accompanying rise in insulin concentration is primarily responsible for the increased proportion of synthase in the I form, 4 -26 but the role of insulin in liver is controversial. In studies using perfused liver 14 -27 and isolated hepatocytes from normal fed rats, 28 can increase synthase I activity and stimulate an increased rate of radioactive glucose incorporation into glycogen independent of added insulin. Similar synthase results can be demonstrated in normal fasted rats pretreated with large amounts of insulin antiserum before glucose was administered, but only transiently.…”

Section: Discussionmentioning

confidence: 97%

“…32 In isolated hepatocytes, insulin alone has been reported to increase the percent synthase I and stimulate glycogen deposition. 28 Others could not demonstrate an independent insulin effect, but did show potentiation of the glucose effect. 30 A major objective of the present study was to determine if an acute rise in insulin concentration plays a significant role in glucose activation of the synthase system or inactivation of the phosphorylase system in normal fed and fasted animals.…”

Section: Discussionmentioning

confidence: 97%

Glycogen Synthase, Synthase Phosphatase, and Phosphorylase Response to Glucose in Somatostatin-Pretreated Intact Rats

et al. 1979

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The response of the glycogen synthase and phosphorylase systems of the liver to intravenous glucose in the presence and absence of short-term somatostatin blockade of insulin secretion was determined in fed and 20-h fasted rats. These enzyme systems regulate glycogen synthesis and degradation, respectively. In the presence of somatostatin, intravenous glucose (1.0 g/kg), promptly (5 min) increased the proportion of synthase in the I (active) form, and the increase was similar to that in animals that had not received somatostatin. In the same animals, phosphorylase a also was decreased, and the decrease was similar in all groups. When a smaller dose of glucose (250 mg/kg) was used that only modestly increased plasma glucose (139 mg/dl) and produced a less than maximal synthase response, insulin (1 U/kg) did not potentiate glucose activation of synthase either in the presence or absence of somatostatin. Phosphorylase a did not change significantly in any group.Glucose, in both the presence and absence of somatostatin, also rapidly (2 min) converted synthase phosphatase from a form inhibited by EDTA to a form not inhibited by EDTA.These data indicate that the synthase and phosphorylase systems in vivo respond primarily to a rise in plasma glucose and not to a simultaneous elevation in plasma insulin. Thus, glucose is regulating its own storage as glycogen in the liver. The effect of glucose on the synthase may be mediated through a conversion of the synthase phosphatase to a form that is not dependent on divalent cation for activity. This form presumably is more active in vivo. DIABETES 28: 231-236, March 1979. I n an intact animal, a high level of circulating glucose results in an increased rate of glucose stored as glycogen in the liver. The rate-limiting step in this process is mediated by glycogen synthase. Glycogen synthase is present in an active form, synthase I, and an inactive form, synthase D. Synthase kinase mediates the conversion of synthase I to synthase D. Conversion of the D form back to the I form is mediated by synthase phosphatase. 1 We recently obtained data by using a ± EDTA assay that suggests that this latter enzyme, or its substrate, also is present in two forms and that interconversion is under metabolite and hormonal control. 2 The rate-limiting step in the degradation of glycogen to glucose is mediated by glycogen phosphorylase. Phosphorylase is likewise interconvertible between an inactive form, phosphorylase b, and an active form, phosphorylase a. A phosphatase catalyzes the conversion of phosphorylase a to phosphorylase b, and a kinase catalyzes the reverse reaction. 1 In vivo, glucose administration stimulates a rapid conversion of liver synthase D to synthase I. 3 -4 However, the relative importance of a rise in glucose concentration and of a rise in insulin concentration in this process has been uncertain. 5 -6 ' 7 -8 Somatostatin rapidly inhibits the secretion of both insulin and glucagon without any apparent direct effect on the liver. 9 -10 Therefore, it should be useful for ...

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“…Previously, Seglen (7) had reported an insulin effect on glycogen metabolism only in cells from starved rats whose glycogen-synthesizing capacity was strongly depressed. However, insulin has since been demonstrated to increase glycogen synthase activity in isolated rat hepatocytes in the presence of glucose (8,9). …”

Section: Preparation Of Hepatocytesmentioning

confidence: 97%

Induction of fatty acid synthetase and acetyl-CoA carboxylase by isolated rat liver cells

Porter¹,

Swenson²

1983

Enzyme Induction and Modulation

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SummaryCurrent studies on the synthesis of long-chain fatty acids by isolated rat liver cells are largely concerned with the regulation of the activity of previously existing acetyl-CoA carboxylase and fatty acid synthetase, and with the regulation of the quantity of these enzymes. These studies have required the development of methods for obtaining high yields of viable hepatocytes that respond to hormonal treatment. Such methods have been developed over the past 10-15 years through the efforts of several laboratories. These studies ha ve also required the development of a method to determine whether a change in the activity of an enzyme is due to a modification of preexisting enzyme or to a change in quantity of that enzyme. The most satisfactory method to use for such studies is immunotitration of enzyme activity.In recent years studies on the regulation of acetyl-CoA carboxylase have largely centered upon the effect of phosphorylation-dephosphorylation on the activity of this enzyme and whether glucagon inhibits the activity of this enzyme through this process. Much data from a number oflaboratories have suggested that glucagon regulates the activity ofthis enzyme through phosphorylation-dephosphorylation. However, several ofthese studies involved the use of crude systems in which competing enzymes and substrates that can significantly interfere with acetyl-CoA carboxylase activity measurements were still present. Hence, a confirmation of these studies needs to be carried out under conditions in which the effects of competing enzymes and substrates are eliminated.Studies on changes in quantity of acetyl-CoA carboxylase and ratty acid synthetase have shown that these enzymes are induced by the fasting and refeeding of animals. They have also shown that insulin stimulates (10-to 3D-fold) the induction ofthese enzymes. This induction appears to be due to a change in the quantity of translatable mRNA which may, in turn, be due to a change in the rate of transcription of the genes coding for these enzymes.

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Studies on the effects of insulin and acetylcholine on activation of glycogen synthase and on glycogenesis in hepatocytes isolated from normal fed rats

Cited by 59 publications

References 12 publications

Intraportal glucose delivery alters the relationship between net hepatic glucose uptake and the insulin concentration.

Intraportal glucose delivery alters the relationship between net hepatic glucose uptake and the insulin concentration.

Glycogen Synthase, Synthase Phosphatase, and Phosphorylase Response to Glucose in Somatostatin-Pretreated Intact Rats

Induction of fatty acid synthetase and acetyl-CoA carboxylase by isolated rat liver cells

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