title: Consistency of the disposition index in the face of diet induced insulin resistance: potential role of FFA.
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.
authors.affiliation: Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America. stefanov@usc.edu
authors.forename: Darko
authors.initials: D
authors.lastname: Stefanovski
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Richey
authors.forename: Orison
authors.initials: O
authors.lastname: Woolcott
authors.forename: Maya
authors.initials: M
authors.lastname: Lottati
authors.forename: Dan
authors.initials: D
authors.lastname: Zheng
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Harrison
authors.forename: Viorica
authors.initials: V
authors.lastname: Ionut
authors.forename: Stella P
authors.initials: SP
authors.lastname: Kim
authors.forename: Isabel
authors.initials: I
authors.lastname: Hsu
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D001835:Body Weight; D003624:Darkness; D004032:Diet; D004285:Dogs; D005215:Fasting / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005247:Feeding Behavior; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin