Insulin Resistance and Insulin Receptors in Hepatic Cirrhosis

Blei, Andrés T.; Robbins, David C.; Drobny, Elaine C.; Baumann, Gerhard; Rubenstein, Arthur H.

doi:10.1016/s0016-5085(82)80127-3

Cited by 52 publications

(10 citation statements)

References 41 publications

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“…The reason for these discrepancies in different studies is unclear, but may indicate a wider spectrum of receptor abnormalities in cirrhosis, reflecting heterogeneity of the patient populations studied and differences in laboratory techniques. However, the failure to find any correlation between insulin receptor binding and insulin insensitivity in this and in our earlier adipocyte study , and in those studies in which some decrease of insulin receptor binding was observed (Blei et a/., 1982;Greco et al, 1980;Regonese et al, 1982), strongly supports the view that a post-receptor defect of insulin action exists in cirrhosis. Why down regulation of the insulin receptor is not observed in the hyperinsulinaemic cirrhotic subject is not known.…”

Section: J Proietto Et Alsupporting

confidence: 67%

Insulin Resistance in Cirrhosis: Evidence for a Post‐receptor Defect

Proietto

Nankervis

Aitken

et al. 1984

Clinical Endocrinology

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Receptor and post-receptor abnormalities of insulin action and their possible role in the insulin resistance of cirrhosis were examined in eight biopsy-proven cirrhotic subjects and eight age-weight matched healthy volunteers. To this end, oral glucose tolerance tests (OGTT), insulin dose response curves and insulin binding to circulating monocytes were determined for each subject. The dose-response curves for the cirrhotic subjects were significantly shifted to the right compared to the control subjects, indicating the presence of insulin insensitivity (ED50 223 +/- 30 versus 64 +/- 8 mU/l respectively; P less than 0.001). The magnitude of the right shift of the insulin-dose response curves correlated significantly (P less than 0.001) with the OGTT 2 h insulin levels (r = 0.74) and the insulin areas under the OGTT curves (r = 0.86). In contrast, insulin responsiveness was marginally elevated in the cirrhotic group (maximal glucose disposal 680 +/- 47 versus 574 +/- 21 ml/m2/min; P less than 0.05). Insulin binding to circulating monocytes was normal in the cirrhotic subjects. It is concluded that the insulin resistance of cirrhosis is due to a post-receptor defect in insulin action which reduces insulin sensitivity but not insulin responsiveness.

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Section: J Proietto Et Alsupporting

confidence: 67%

Insulin Resistance in Cirrhosis: Evidence for a Post‐receptor Defect

Proietto

Nankervis

Aitken

et al. 1984

Clinical Endocrinology

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“…In a group of alcoholic cirrhotics, monocyte insulin binding was found to be reduced (25). Blei and co-workers observed no reduction in monocyte insulin binding in a group of 16 patients with cirrhosis of varying etiology but found that the five hyperinsulinemic cirrhotics had reduced monocyte insulin binding (26). In a group of Japanese patients with unspecified liver disease, monocyte insulin binding was found to be reduced in direct proportion to the severity of impairment of glucose tolerance (27), whereas in a large group of Caucasian cirrhotics, monocyte insulin binding was normal in those subjects with impaired glucose tolerance and was reduced only in those subjects with normal glucose tolerance (Pinieweski, M. et al, unpublished observations).…”

Section: Discussionmentioning

confidence: 98%

Insulin action in cirrhosis

et al. 1985

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In vivo insulin sensitivity and adipocyte insulin binding and action were assessed in 16 patients with histologically proven hepatic cirrhosis and 11 age-, weight- and sex-matched normal control subjects. The cirrhotic group displayed impaired oral glucose tolerance, despite an exaggerated serum immunoreactive insulin response, and in vivo insulin resistance as assessed both by the euglycemic hyperinsulinemic clamp and the glucose-insulin infusion techniques. Adipocytes of the cirrhotic patients bound significantly less insulin than those of the control subjects (2.21 +/- 0.12% vs. 2.64 +/- 0.13%; p less than 0.05). Although the adipocytes from the cirrhotic patients were less sensitive to insulin stimulation in vitro (half-maximal stimulation at 60.0 +/- 8.0 vs. 21.8 +/- 3.3 pM; p less than 0.001), they exhibited higher maximum rates of lipogenesis. Comparison of the responses of the alcoholic, primary biliary cirrhosis and cryptogenic subgroups suggested pronounced differences in the maximum rates of lipogenesis. There were significant negative correlations between specific binding to adipocytes and both fasting serum immunoreactive insulin and in vivo insulin resistance as assessed by glucose-insulin infusion. Monocyte insulin binding was normal in the cirrhotic group and did not correlate with in vivo insulin resistance. It is concluded that both binding and postbinding defects in insulin target organ cells contribute to the marked in vivo insulin resistance of hepatic cirrhosis.

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“…In addition, nonalcoholic fatty liver disease is often complicated with increased adiposity, which leads to hyperinsulinemia both in the non-cirrhotic and cirrhotic population [38]. Chronic hyperinsulinemia then leads to insulin resistance via the desensitization and downregulation of insulin receptors [11][12][13]. As it was already mentioned, insulin resistance is both an early process in the natural history of liver disease, often preceding the onset of liver cirrhosis, and a remarkable risk factor of death or transplantation [9,18].…”

Section: Discussionmentioning

confidence: 99%

“…Both disease progression with further hepatocellular dysfunction and portal hypertension-related portosystemic shunting of insulin aggravate hyperinsulinemia [10,11]. Insulin resistance then occurs via insulin receptor desensitization and downregulation due to chronic hyperinsulinemia [11][12][13]. Transition to overt diabetes mellitus is primarily driven by beta-cell dysfunction and the inability to compensate for the insulin resistance [14].…”

Section: Introductionmentioning

confidence: 99%

Leptin as a Key Player in Insulin Resistance of Liver Cirrhosis? A Cross-Sectional Study in Liver Transplant Candidates

Košuta

Mrzljak

Kolarić

et al. 2020

JCM

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Insulin resistance is associated with increased risk of death and liver transplantation in the cirrhotic population, independent of disease aetiology. However, factors accounting for insulin resistance in the context of cirrhosis are incompletely understood. This study aimed to investigate the association between adiponectin and leptin with insulin resistance in cirrhotic patients and to assess the influence of disease severity on insulin resistance and metabolic status. This cross-sectional study included 126 non-diabetic cirrhotic transplant candidates. The homeostasis model assessment 2 model was used to determine the insulin resistance index, and fasting adiponectin, leptin, insulin, c-peptide, glucose, HbA1c, and lipid profiles were analysed. Insulin resistance was detected in 83% of subjects and associated with increased leptin, fasting plasma glucose and body mass index, and lower triglyceride levels. Logistic regression analysis identified leptin and triglycerides as independent predictors of insulin resistance (OR 1.247, 95% CI 1.076–1.447, p = 0.003; OR 0.357, 95% CI 0.137–0.917, p = 0.032.). Leptin levels remained unchanged, whereas adiponectin levels increased (p < 0.001) with disease progression, and inversely correlated with HbA1c (ρ = −0.349, p < 0.001). Our results indicate that leptin resistance, as indicated by elevated leptin levels, can be regarded as a contributing factor to insulin resistance in cirrhotic patients, whereas triglycerides elicited a weak protective effect. Progressively increasing adiponectin levels elicited a positive effect on glucose homeostasis, but not insulin sensitivity across disease stages.

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Insulin Resistance and Insulin Receptors in Hepatic Cirrhosis

Cited by 52 publications

References 41 publications

Insulin Resistance in Cirrhosis: Evidence for a Post‐receptor Defect

Insulin Resistance in Cirrhosis: Evidence for a Post‐receptor Defect

Insulin action in cirrhosis

Leptin as a Key Player in Insulin Resistance of Liver Cirrhosis? A Cross-Sectional Study in Liver Transplant Candidates

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