Time course of change in sucrose-induced insulin resistance,
triglyceride concentration, and liver fatty acid composition.
Pagliassotti, Michael J., Piper A. Prach, Thad A. Koppenhafer, David
A. Pan.
Section of Pediatric Nutrition and Center for Human Nutrition,
University of Colorado Health Sciences Center, Denver, CO. 80262;
Department of Endocrinology, Royal Prince Alfred Hospital, Sydney,
NSW 2050, Australia
APStracts 3:0161R, 1996.
In the present study the euglycemic, hyperinsulinemic clamp technique
with 3-3H-glucose was used to examine the time course of change in
sucrose-induced insulin resistance in liver (reduced suppression of
hepatic glucose production) and muscle (reduced glycogen synthesis).
In addition, changes in plasma and tissue triglyceride (TG)
concentration, and liver fatty acid composition were assessed over
time. Male rats (n=8-10/group/time point) were fed a high starch diet
(ST, 68% of calories as corn starch) for 2 wk and then were
equicalorically fed ST or a high sucrose diet (SU, 68% of calories as
sucrose) for 1, 2, 5, or 8 wk. Body weight (318+/-5g, 367+/-7g,
491+/-7g, 525+/-6g) and percent body fat were similar between ST and
SU at 1, 2, 5, and 8 wk, respectively. The glucose infusion rate
(GIR) at an insulin level of 113+/-6 [mu]U/ml was significantly
(p<0.05) lower in SU (9.2+/-0.9, 7.4+/-0.5, 6.2+/-1.0, 6.0+/-0.9
mg.kg-1.min-1) vs. ST (15.1+/-1.7, 15.7+/-0.7, 14.7+/-0.9, 14.2+/-0.9
mg.kg-1.min-1) at 1, 2, 5, and 8 wk, respectively. Reduced
suppression of hepatic glucose production accounted for 85, 50, 45,
and 40% of the reduction in GIR at these same time points. Tracer
estimated muscle glycogen synthetic rates were reduced (p<0.05
vs. ST) in SU at 2, 5, and 8 wk. Fasting plasma TG concentration was
inversely related (r=-0.79, p<0.001) to muscle glycogen
synthesis, and liver TG concentration was positively related (r=0.59,
p<0.01) to hepatic glucose production when the two diet groups
were examined together. Liver fatty acid composition was similar
between diet groups at all time points. In summary, a high sucrose
diet produced insulin resistance in liver prior to muscle.
Triglyceride concentration appears to be related to sucrose-induced
insulin resistance in liver and muscle.
Received 24 January 1996; accepted in final form 24 April 1996.
APS Manuscript Number R37-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96