Islet amyloid polypeptide in the control of food intake : An experimental study in the rat
Author: Arnelo, Urban
Date: 1997-12-19
Location: Hörsalen, plan 4, Novum
Time: 9.00
Abstract
Control of food intake and satiety are physiologically complex processes,
thatonly partly are understood. Several hormonal peptides have been
proposed to mediatesatiety. Islet amyloid polypeptide (IAPP) is a
recently discovered 37 amino acidpeptide, mainly produced by the
pancreatic ß-cells. Initially, IAPP was shownto impair glucose tolerance
at supra-physiological plasma concentrations and wasspeculated to be
involved in the development of type-2 diabetes. More recent studiesof
IAPP administration at pharmacological doses, demonstrate that IAPP can
inhibitfood intake in the rat. In the present study the anorectic effect
of LAPP is furtherevaluated, with the hypothesis that IAPP is a satiety
factor that plays a hormonalrole in the control of food intake.
To test the hypothesis a series of in vivo experiments in rats were
performed.IAPP was administered both acutely and chronically. Food intake
was registered eithermanually or continuously by computer, enabling
analysis of meal patterns. A novelindwelling aortic catherization
technique was developed. This new technique allowedfrequent and rapid
blood sampling for up to two months. Plasma levels of IAPP weredetermined
by radioimmunoassay in all studies. In addition, the catheterization
techniquemade it possible to in the same animals determine the threshold
dose of IAPP forsuppression of food intake, the plasma response to this
IAPP dose, and compare thisresponse to plasma concentrations of IAPP
obtained during feeding. Furthermore, theeffect of IAPP on peripheral
glucose utilization was measured by hyperinsulinemiceuglycernic clamp at
plasma con-centrations of IAPP that reduced food intake. Inaddition, the
response to anorectic IAPP doses on satiety related neurotransmittersand
neuropeptides was investigated.
Both acute and chronic IAPP administration potently inhibited food intake
in adose response manner. Inhibition of food intake occurred at lower
doses than previouslyreported. Analysis of meal pattern following both
acute and chronic IAPP administrationrevealed that the reduced food
intake was caused by a decreased meal frequency ratherthan meal size. In
the chronic meal pattern experiment, the effects were most
prominentduring the light phase. It was demonstrated that plasma
concentrations of IAPP duringfeeding were not sufficient to inhibit food
intake. However, the threshold dose resultedin circulating IAPP levels
that were close to those levels that were observed duringphysiological
conditions and well within the range of what has been reported in
anorecticpancreatic cancer patients. Chronic administration of low
anorectic doses of IAPPdid not induce hyperglycemia or insulin
resistance, and did not alter levels of neurotransmittersand
neuropeptides in the hypothalamus, hippocampus, striatum, left cortex,
and rightcortex of the rat brain.
In conclusion, IAPP potently and dose-dependently inhibits food intake by
reducingmeal frequency. The postprandial rise in plasma IAPP that was
obtained in this studyis not sufficient to reduce food intake, but
exogenously administered IAPP that producesplasma concentrations similar
to what is observed in pancreatic cancer patients inhibitsfood intake.
This study provides evidence to suggest that the anorectic effect ofIAPP
can not be explained by a reduction in glucose utilization or marked,
sustained,changes in neurotransmitters or neuropeptides in rat brain.
Keywords: body weight, glucose metabolism, IAPP, meal patterns,
monoamines, neuropeptides,radioimmunoassay, rats, satiety
ISBN 91-628-2778-2
Issue date: 1997-11-28
Publication year: 1997
ISBN: 91-628-2778-2
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