title: Effects of islet amyloid polypeptide on hepatic insulin resistance and glucose production in the isolated perfused rat liver.
abstract: 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(-7) mol/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 x 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 x 10(-11) mol/l) increased integral hepatic glucose release within 84 min (763.4 +/- 161.7 vs -25.7 +/- 73.2 mumol x 100 g body weight-1 in the control group, p less than 0.001), while insulin (100 mU/l) decreased the glucagon-stimulated glucose production (395.2 +/- 180.0 mumol x 100 g body weight-1, p less than 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 mumol x 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 mumol.min-1 x 100 g body weight-1).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Ist Medical Department, University of Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Roden
authors.forename: K
authors.initials: K
authors.lastname: Liener
authors.forename: C
authors.initials: C
authors.lastname: Fürnsinn
authors.forename: P
authors.initials: P
authors.lastname: Nowotny
authors.forename: U
authors.initials: U
authors.lastname: Hollenstein
authors.forename: H
authors.initials: H
authors.lastname: Vierhapper
authors.forename: W
authors.initials: W
authors.lastname: Waldhäusl
mesh_terms: D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D007773:Lactates; D008112:Liver Glycogen; D005934:Glucagon; D000242:Cyclic AMP