Time course of insulin resistance associated with feeding dogs a
high fat diet.
Rocchini, Albert P., Paul Marker, Tereza Cervenka.
Division of Pediatric Cardiology, Department of Pediatrics,
University of Minnesota, Minneapolis, MN 55455
APStracts 3:0135E, 1996.
The current study evaluated both the time course of insulin resistance
associated with feeding dogs a high fat diet and the relationship
between the development of insulin resistance and the increase in
blood pressure that also occurs. Twelve adult mongrel dogs were
chronically instrumented and randomly assigned to either a control
diet group (n=4) or a high fat diet group (n=8). Insulin-resistance
was assessed by a weekly, single dose (2 mU/kg x min) euglycemic
hyperinsulinemic clamp on all dogs. Feeding dogs a high fat diet was
associated with a 3.7+/-0.5 kg increase in body weight, a 20+/-4 mm
Hg increase in mean blood pressure, a reduction in insulin mediated
glucose uptake (decreasing from 72+/-6 [mu]mol/kg x min before to
49+/-7 at one week, 29+/-3 at 3 weeks and 30+/-2 [mu]mol/kg x min at
6 weeks of the high fat diet, p<0.01) and a reduced insulin
mediated increase in cardiac output. In eight dogs (4 high fat and 4
control ), the dose response relationship of insulin induced glucose
uptake also was studied. The whole body glucose uptake dose response
curve was shifted to the right and the rate of maximal whole body
glucose uptake was significantly decreased (p<0.001). Finally,
we observed a direct relationship between the high fat diet induced
weekly increase in mean arterial pressure and the degree to which
insulin-resistance developed. In summary the current study documents
that feeding dogs a high fat diet causes the rapid development of
insulin resistance that is the result of both a reduced sensitivity
and a reduced responsiveness to insulin.
Received 14 August 1995; accepted in final form 19 February 1996.
APS Manuscript Number E388-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996