Insulin action in cirrhosis

Authors

  • Dr. R. Taylor M.D.,

    Corresponding author
    1. Departments of Clinical Biochemistry and Metabolic Medicine and Medicine, Newcastle University Hospitals, Newcastle upon Tyne, United Kingdom
    • Department of Clinical Biochemistry and Metabolic Medicine, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, United Kingdom
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    • MRC Training Fellowship.

  • R. J. Heine,

    1. Departments of Clinical Biochemistry and Metabolic Medicine and Medicine, Newcastle University Hospitals, Newcastle upon Tyne, United Kingdom
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  • J. Collins,

    1. Departments of Clinical Biochemistry and Metabolic Medicine and Medicine, Newcastle University Hospitals, Newcastle upon Tyne, United Kingdom
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  • O. F. W. James,

    1. Departments of Clinical Biochemistry and Metabolic Medicine and Medicine, Newcastle University Hospitals, Newcastle upon Tyne, United Kingdom
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  • K. G. M. M. Alberti

    1. Departments of Clinical Biochemistry and Metabolic Medicine and Medicine, Newcastle University Hospitals, Newcastle upon Tyne, United Kingdom
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Abstract

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 < 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 < 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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