Effects of islet amyloid polypeptide on hepatic insulin resistance and glucose production in the isolated perfused rat liver.
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)
Roden
M
M
Ist Medical Department, University of Vienna, Austria.
Liener
K
K
Fürnsinn
C
C
Nowotny
P
P
Hollenstein
U
U
Vierhapper
H
H
Waldhäusl
W
W
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
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D007773:Lactates; D008112:Liver Glycogen; D005934:Glucagon; D000242:Cyclic AMP