Lack of effect of islet amyloid polypeptide on hepatic glucose output in the in situ-perfused rat liver.
Islet amyloid polypeptide (IAPP), a novel peptide isolated from islet amyloid deposits in patients with insulinoma and non-insulin-dependent diabetes mellitus (NIDDM), has been reported to be cosecreted with insulin from pancreatic beta cells and to inhibit glucose uptake and glycogen synthesis in muscle tissue in vitro. We investigated the effects of the synthesized, rat-amidated form of IAPP on hepatic glucose output, and IAPP extraction, using an in situ flow-through perfusion system in rats to elucidate the actions of IAPP on the liver. The IAPP (10(-8) mol/L) alone had no effects on the hepatic glucose release. Infusion of 6 x 10(-11) mol/L glucagon alone resulted in an expected elevation in glucose production (30.0 +/- 1.7 mumol/35 min/g liver). Insulin (3 x 10(-10) mol/L) submaximally decreased the glucagon-stimulated glucose production to 73% (from 30.0 +/- 1.7 to 22.0 +/- 1.4 mumol/35 min/g liver; n = 7, P less than .01). A simultaneous infusion of 10(-8) mol/L IAPP did not influence the glucagon-stimulated glucose production (27.6 +/- 1.2 mumol/35 min/g liver) or the insulin-dependent inhibition of glucagon-stimulated glucose production (22.6 +/- 1.3 mumol/35 min/g liver). IAPP extraction by the liver in a single passage was minimal, in contrast to approximately 50% hepatic insulin extraction. These results indicate that IAPP does not play any important role in modulating glycogen metabolism in the liver.
Nishimura
S
S
First Department of Medicine, Wakayama University of Medical Science, Japan.
Sanke
T
T
Machida
K
K
Bessho
H
H
Hanabusa
T
T
Nakai
K
K
Nanjo
K
K
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D005934:Glucagon; D005947:Glucose