Glucose intolerance in liver cirrhosis

Riggio, Oliviero; Merli, Manuela; Cangiano, C.; Capocaccia, Riccardo; Cascino, A.; Lala, A.; Leonetti, Frida; Mauceri, M.; Pepe, M; Fanelli, Filippo Rossi; Savioli, Massimiliano; Tamburrano, G.; Capocaccia, L.

doi:10.1016/0026-0495(82)90103-2

Cited by 71 publications

(25 citation statements)

References 26 publications

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“…Such solutions are currently used in the parentheral nutrition of patients with liver failure, a condition often associated to impaired glucose tolerance, insulin-resistance, hyperinsulinaemia and hyper-glucagonaemia [10]. As hyperinsulinaemia may be further increased by glucose and amino acids often infused in combination in these patients, a clinical situation similar to the experimental conditions of the present study is likely to occur.…”

Section: Discussionmentioning

confidence: 89%

Hyperaminoacidaemia reduces insulin-mediated glucose disposal in healthy man

et al. 1985

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Summary.To determine whether hyperaminoacidaemia may modify insulin-mediated glucose disposal, normal subjects were studied with the euglycaemic glucose-clamp technique, with or without an amino acid infusion, at a rate sufficient to duplicate the plasma concentration of most amino acids. Steady-state glucose infusion rates to maintain euglycaemia were 36% lower during hyperaminoacidaemia (7.3 + 1.0 versus 11.4 _+ 0.8 mg. kg-1. rain-2, p < 0.01) at comparable insulin concentrations (92 + 6 versus 93 + 7 mU/1 respectively). Thus, under conditions of hyperinsulinaemia, amino acids could compete with glucose as metabolic fuels.Key words: Hyperaminoacidaemia, euglycaemic hyperinsulinaemic clamp, glucose disposal.During an euglycaemic, hyperinsulinaemic clamp, insulin-sensitivity is often expressed as the glucose infusion rate necessary to maintain euglycaemia [1]. However, many other metabolic changes occur under hyperinsulinaemic conditions. Among them, plasma free fatty acid, ketone body and amino acid concentrations decrease markedly. Since competition between substrates as metabolic fuels may occur [2], glucose uptake in vivo could be indirectly enhanced by the concomitant decrease in concentration and utilization of other substrates. Therefore, "insulin sensitivity", measured with the euglycaemic, hyperinsulinaemic clamp technique, could be modified by preventing the fall and/or increasing the concentrations of the substrates suppressed by insulin.Recently, increased plasma free fatty acid concentrations have been shown to reduce insulin-mediated glucose disposal [3]. However, it is not known whether in vivo increments in plasma amino acid concentrations may also affect glucose disposal rates. Therefore, the aim of the present study was to evaluate the effect ofhyperaminoacidaemia on insulin-mediated glucose utilization in postabsorptive normal subjects. Subjects and methodsHealthy subjects (aged 21-57 years) were studied in the post-absorptive state. All subjects had normal body weight, and consumed their usual weight-maintaining diet ( -30 kcal/kg per day, containing 50% of total calories as carbohydrates, 20% as protein and 30% as fat) for at least 3 days prior to the study. The details and the potential risks of the study were explained, and each subject signed an informed written consent before the initiation of the study. The subjects were divided into two groups. In group A, (five males, one female, age: 28 + 3 years, body mass index: 22.9+0.8), an euglycaemic-hyperinsulinaemic clamp was performed for 180 rain, as previously described [4]. Insulin was infused by means of a Harvard Pump (Harvard Apparatus, Millis, MA, USA), at the rate of 0.05 U.m 2-' .min -1. Blood glucose concentration was maintained by means of the Biostator (Miles Laboratories, Elkhart, IN, USA) [4] at 4.72 + 0.11 mmol/1 (coefficient of variation: ~11%). In group B (four males, one female, age: 35 + 5 years, body mass index: 22.0 + 0.7) the subjects were studied as for group A, with the addition of an amino acid infusion for the sam...

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Section: Discussionmentioning

confidence: 89%

Hyperaminoacidaemia reduces insulin-mediated glucose disposal in healthy man

et al. 1985

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“…Carbohydrate intolerance in cirrhosis of the liver has been extensively demonstrated (1)(2)(3)(4)(5)(6)(7)(8), ever since Naunyn first coined Some parts of this study were presented at the 2nd International Symposium on Insulin Receptors, Rome, Italy, September 1983.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of insulin resistance in human liver cirrhosis. Evidence of a combined receptor and postreceptor defect.

Cavallo‐Perin¹,

Cassader²,

Bozzo³

et al. 1985

J. Clin. Invest.

125

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“…The role of extrahe patic shunting of insulin in reducing the insulin concentration, to which the hepato cytes are exposed, has not been investigated. Despite correlation of total body insulin re sistance with the severity of the liver disease, the importance of intrahepatic insulin resis tance in determining total body insulin resis tance is not well established [30,58,59,62,[64][65][66][67][68][69], Extrahepatic insulin resistance is sug gested in cirrhotic patients by direct in vitro measurement on adipose and muscle cells [62][63][64][65][66][67][68][69] and by abnormal forearm glucose uptake [71][72][73], Furthermore, the insulin re ceptor also mediates branched-chain amino acid uptake in peripheral tissue (primarily muscle). Since branched chain amino acids are not removed significantly by the liver, the serum clearance of these amino acids in re sponse to elevated insulin levels is another means of assessing extrahepatic insulin resis tance [57,62,63], Marked branched-chain amino acid intolerance has been demon strated in patients with chronic liver disease and correlates with the degree or glucose intolerance and insulin resistance [57,62,63], Extrahepatic insulin resistance, primarily in muscle and adipose tissue, could be me diated by prereceptor, receptor or postrecep tor abnormalities [74][75][76][77], Prereceptor de fects have not been recognized [69].…”

Section: Secondary Glucose Intolerance and Insulin-dependent Diabetesmentioning

confidence: 99%

“…The degree of insulin resistance correlates with hepatic factors such as the severity of liver disease [52,53] and nonhe patic factors such as adipose and muscle tis sue responsiveness to insulin [63][64][65][66][67][68][69][70][71][72][73]. Thus, the major site of insulin resistance may be hepatic or extrahepatic [52][53][54][55][56][57][58][63][64][65][66][67][68][69][70][71][72][73].…”

Section: Secondary Glucose Intolerance and Insulin-dependent Diabetesmentioning

confidence: 99%