Document Type
Journal Article
Date of this Version
3-30-2011
Publication Source
PLoS ONE
Volume
6
Issue
3
Start Page
e18134
DOI
10.1371/journal.pone.0018134
Abstract
Objective
Insulin resistance induces hyperinsulinemic compensation, which in turn maintains almost a constant disposition index. However, the signal that gives rise to the hyperinsulinemic compensation for insulin resistance remains unknown.
Methods
In a dog model of obesity we examined the possibility that potential early-week changes in plasma FFA, glucose, or both could be part of a cascade of signals that lead to compensatory hyperinsulinemia induced by insulin resistance.
Results
Hypercaloric high fat feeding in dogs resulted in modest weight gain, and an increase in adipose tissue with no change in the non-adipose tissue size. To compensate for the drop in insulin sensitivity, there was a significant rise in plasma insulin, which can be attributed in part to a decrease in the metabolic clearance rate of insulin and increased insulin secretion. In this study we observed complete compensation for high fat diet induced insulin resistance as measured by the disposition index. The compensatory hyperinsulinemia was coupled with significant changes in plasma FFAs and no change in plasma glucose.
Conclusions
We postulate that early in the development of diet induced insulin resistance, a change in plasma FFAs may directly, through signaling at the level of β-cell, or indirectly, by decreasing hepatic insulin clearance, result in the observed hyperinsulinemic compensation.
Copyright/Permission Statement
© 2011 Stefanovski, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Recommended Citation
Stefanovski, D., Richey, J. M., Woolcott, O., Lottati, M., Zheng, D., Harrison, L. N., Ionut, V., Kim, S. P., & Bergman, R. N. (2011). Consistency of the Disposition Index in the Face of Diet Induced Insulin Resistance: Potential Role of FFA. PLoS ONE, 6 (3), e18134-. http://dx.doi.org/10.1371/journal.pone.0018134
Date Posted: 22 December 2016
This document has been peer reviewed.
Comments
At the time of publication, author Darko Stefanovski was affiliated with the University of Southern California. Currently, he is a faculty member at the University of Pennsylvania's School of Veterinary Medicine.