In Vivo Regulation of Liver and Skeletal Muscle Glycogen Synthase Activity by Glucose and Insulin

Kruszynska, Yolanta T.; Home, Philip; Alberti, K. G. M. M.

doi:10.2337/diab.35.6.662

Cited by 53 publications

(21 citation statements)

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“…5; r = 0.89, p < 0.001) in the cirrhotic patients suggests they can achieve peripheral insulin levels in response to intravenous glucose that, despite their insulin insensitivity, result in a glucose disposal rate appropriate to the prevailing blood glucose level. The strong relationship between the peripheral insulin concentration and clamp glucose disposal is consistent with the observation that -under glucose clamp conditions with peripheral venous glucose administrationvery little glucose is taken up by liver, skeletal muscle being the major determinant of whole-body glucose disposal (38)(39)(40).…”

Section: Discussionsupporting

confidence: 85%

“…Insulin sensitivity in our subjects was measured by the euglycemic clamp technique using an insulin infusion rate considerably higher than that shown to suppress hepatic glucose production completely in both cirrhotic patients and controls (6,17). Because only a small fraction of the infused glucose is taken up by liver (38)(39)(40), the lower glucose requirement during the euglycemic clamp (Fig. 2) implies marked peripheral tissue insulin resistance in our patients.…”

Section: Discussionmentioning

confidence: 87%

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Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis

1991

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Hepatic insulin extraction is difficult to measure in humans; as a result, the interrelationship between defective insulin secretion and insulin insensitivity in the pathogenesis of glucose intolerance in cirrhosis remains unclear. To reassess this we used recombinant human C-peptide to measure C-peptide clearance in cirrhotic patients and controls and thus derive C-peptide and insulin secretion rates after a 75-gm oral glucose load and during a 10 mmol/L hyperglycemic clamp. Cirrhotic patients were confirmed as insulin-insensitive during a euglycemic clamp (glucose requirement: 4.1 +/- 0.1 mg/kg/min vs. 8.1 +/- 0.5 mg/kg/min; p less than 0.001), which also demonstrated a low insulin metabolic clearance rate (p less than 0.001). Although intolerant after oral glucose, the cirrhotic patients had glucose requirements identical to those of controls during the hyperglycemic clamp (cirrhotic patients: 6.1 +/- 1.0 mg/kg/min; controls: 6.3 +/- 0.7 mg/kg/min), suggesting normal intravenous glucose tolerance. C-peptide MCR was identical in cirrhotic patients (2.93 +/- 0.16 ml/min/kg) and controls (2.96 +/- 0.24 ml/min/kg). Insulin secretion was higher in cirrhotic patients, both fasting (2.13 +/- 0.26 U/hr vs. 1.09 +/- 0.10 U/hr; p less than 0.001) and from min 30 to 90 of the hyperglycemic clamp (5.22 +/- 0.70 U/hr vs. 2.85 +/- 0.22 U/hr; p less than 0.001). However, with oral glucose the rise in serum C-peptide concentration was relatively delayed, and the insulin secretion index (secretion/area under 3-hr glucose curve) was not elevated. Hepatic insulin extraction was reduced both in fasting and during the hyperglycemic clamp (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 87%

Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis

1991

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“…It may be speculated that under these conditions insulin-controlled metabolic processes in muscle which are connected to alanine production are altered on the basis of the chronically elevated insulin action which is more or less reversed by portal insulin administration. An elevated peripheral insulin action would stimulate the muscular uptake of glucose [25,26], thereby feeding glycogen synthesis and glycolysis. Thus, lactate becomes the main product of glucose utilisation, even in resting muscle; this can be seen from the high circulating lactate levels.…”

Section: Discussionmentioning

confidence: 99%

The effect of prehepatic insulin administration on alanine flux rates in diabetic dogs

et al. 1987

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The in vivo flux rates of glucose (6-3H-glucose) and of alanine (U-14C-alanine) were measured in insulin-dependent chronically diabetic dogs which were infused with insulin employing a bedside-type artificial B cell and either the peripheral or the portal venous route. In comparison with non-diabetic control animals the diabetic dogs had near-normal patterns of glucose metabolism and pancreatic glucagon regardless of the route of insulin administration. They also showed reduced basal portal but moderately elevated peripheral insulin levels on peripheral and near-normal peripheral values on portal insulin infusion. Both concentration and production rates of alanine were reduced on peripheral (0.142 +/- 0.016 mmol/l, 4.73 +/- 0.49 mumol.kg-1.min-1, p less than 0.05) but normal on portal insulin (0.206 +/- 0.030 mmol/l, 6.33 +/- 0.63 mumol.kg-1.min-1). The alanine clearance was slightly elevated or normal in the diabetic dogs, and the glucose production from alanine showed a strongly delayed response to an exogenous glucose load on either route of insulin administration. It is concluded that the peripheral hyperinsulinism during posthepatic insulin administration stimulates glucose utilisation to a normal extent, but inhibits the provision of amino groups in resting muscle. Alanine synthesis is thereby reduced, and the carbon moieties are shunted from glucose into circulating lactate. Long-term studies are needed to elucidate the role of the liver under these conditions.

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“…Under these conditions, VLDLtriglyceride turnover fell by 20-30% in both normal and insulin over-treated rats, and at the end of the clamp was significantly less in the chronically insulin over-treated group (Table 2). Since, in the insulin overtreated animals, glucose requirement during the clamp was decreased, and as only a small proportion of infused glucose is stored as glycogen in the rat [29], a decreased supply of 3-carbon intermediates (lactate, pyruvate, alanine) for hepatic de novo lipogenesis might appear to be the important determinant of VLDL production as in the fasting state. Insulin insensitivity in the lipogenic pathway within the liver cannot, however, be ruled out.…”

Section: Discussionmentioning

confidence: 99%

Very low density lipoprotein metabolism after insulin over‐treatment and during a euglycaemic clamp

Kruszynska

Home

Alberti

1987

Eur J Clin Investigation

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The disturbance of very low density lipoprotein (VLDL) metabolism that occurs as a result of intensive insulin treatment and during a euglycaemic clamp have been investigated in a rat model. Normal rats were maintained with fed blood glucose levels below 5 mmol l-1 for 8 weeks by subcutaneous insulin injections (normal fed levels 5.8 +/- 0.4 (SD) mmol l-1). Glucose requirement to maintain a glucose clamp was significantly reduced (116 +/- 3 mumol min-1 kg-1 (SE) vs. 173 +/- 5 mumol min-1 kg-1, P less than 0.001), compared with weight-matched normal control rats. In the fasting state (blood glucose 3.5 +/- 0.2 mmol l-1 vs. 3.9 +/- 0.1 mmol l-1, NS) plasma non-esterified fatty acid levels were reduced. Fasting VLDL-triglyceride turnover, measured by bolus injection of 14C-VLDL, was also lower (3.17 +/- 0.12 mumol min-1 kg-1 vs. 3.50 +/- 0.07 mumol min-1 kg-1, P less than 0.05). Despite decreased turnover, insulin over-treated rats had normal plasma triglyceride concentrations indicating a removal defect. At the end of a 3-h euglycaemic clamp, plasma triglyceride concentrations and VLDL-triglyceride turnover were decreased in both normal control and insulin over-treated animals, and turnover remained significantly lower in the insulin over-treated rats (2.59 +/- 0.13 mumol min-1 kg-1 vs. 3.08 +/- 0.10 mumol min-1 kg-1, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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In Vivo Regulation of Liver and Skeletal Muscle Glycogen Synthase Activity by Glucose and Insulin

Cited by 53 publications

References 0 publications

Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis

Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis

The effect of prehepatic insulin administration on alanine flux rates in diabetic dogs

Very low density lipoprotein metabolism after insulin over‐treatment and during a euglycaemic clamp

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