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

This article is under a Creative Commons Attribution 4.0 license. This license permits any user to download, print out, copy, archive, and distribute the article, so long as appropriate credit is given to the authors and source of the work.

Comments

At the time of publication, author Darko Stefanovski was affiliated with University of Southern California. Currently, he is a faculty member at the School of Veterinary Medicine at the University of Pennsylvania.

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Date Posted: 22 December 2016

This document has been peer reviewed.