Effects of islet amyloid polypeptide on hepatic insulin resistance and glucose production in the isolated perfused rat liver (original) (raw)

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The impact of (pancreatic) islet amyloid polypeptide on glucose metabolism and insulin sensitivity was examined in isolated rat livers perfused in a non-recirculating system. Continuous infusion of 10−7mol/l islet amyloid polypeptide affected neither basal nor glucagon (10−9 mol/l)-stimulated glucose output by livers from fed rats, but it did increase the hepatic cyclic AMP release within 44 min (7.91±12.07 vs control: 0.07±0.03 pmol·100 g body weight−1). The effect of the peptide on the ability of insulin to inhibit glucagon-induced hepatic glycogenolysis was measured in three experimental groups (n = 6). As expected glucagon (7×10−11 mol/l) increased integral hepatic glucose release within 84 min (763.4±161.7 vs −25.7±73.2 μmol · 100 g body weight−1 in the control group, p<0.001), while insulin (100 mU/l) decreased the glucagon-stimulated glucose production (395.2±180.0 μmol·100 g body weight−1, p<0.01). Simultaneous infusion of 10−7 mol/l islet amyloid polypeptide however, was not able to reverse insulin-dependent inhibition of glucagon-stimulated hepatic glucose output (370.0±102.5 μmol·100 g body weight−1, NS) or to enhance lactate-induced gluconeogenesis of livers from 24 h fasted rats (n = 8). The glucose production stimulated by 10−9 mol/l glucagon was slightly greater in islet amyloid polypeptide-pre-treated livers than in a control group without addition of islet amyloid polypeptide (5 min: 3.60±3.36 vs 1.67±1.28 μmol·min−1·100 g body weight−1). These results suggest that islet amyloid polypeptide neither directly affects hepatic glycogenolysis nor causes insulin resistance to hormone-sensitive glucose production, but may increase the size of the hepatic glycogen pool by enhancing gluconeogenesis.

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Authors and Affiliations

  1. Ist Medical Department, Division of Clinical Endocrinology and Diabetology, University of Vienna, Austria
    M. Roden, K. Liener, C. Fürnsinn, P. Nowotny, U. Hollenstein, H. Vierhapper & W. Waldhäusl

Authors

  1. M. Roden
  2. K. Liener
  3. C. Fürnsinn
  4. P. Nowotny
  5. U. Hollenstein
  6. H. Vierhapper
  7. W. Waldhäusl

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Roden, M., Liener, K., Fürnsinn, C. et al. Effects of islet amyloid polypeptide on hepatic insulin resistance and glucose production in the isolated perfused rat liver.Diabetologia 35, 116–120 (1992). https://doi.org/10.1007/BF00402542

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