Insulin Resistance is Associated with Diminished Endoplasmic Reticulum Stress Responses in Adipose Tissue of Healthy and Diabetic Subjects

  1. Lucas Ferrer, M.D.3
  1. 1Division of Endocrinology/Diabetes/Metabolism
  2. 2Clinical Research Center
  3. 3Department of Surgery, Temple University School of Medicine, Philadelphia, PA
  1. Corresponding Author: Guenther Boden, E-mail: bodengh{at}tuhs.temple.edu

Abstract

We have recently shown that insulin increased ER stress in human adipose tissue. The effect of insulin resistance on ER stress is not known. It could be decreased, unchanged or increased, depending on whether insulin regulates ER stress via the metabolic/phosphoinositide 3-kinase (PI3K) or alternate signaling pathways.

To address this question, we have examined effects of lipid induced insulin resistance on insulin stimulation of ER stress.

mRNAs of several ER stress markers were determined in fat biopsies obtained before and after 8 hour hyperglycemic-hyperinsulinemic clamping in 13 normal subjects and in 6 chronically insulin resistant patients with type 2 diabetes (T2DM).

In normal subjects, hyperglycemia-hyperinsulinemia increased post/pre mRNA ratios of several ER stress markers (determined by ER stress pathway array and by individual RT-PCR). Lipid infusion was associated with inhibition of the PI3K insulin signaling pathway and with a decrease of hyperinsulinemia induced ER stress responses. In chronically insulin resistant patients with T2DM, hyperglycemic-hyperinsulinemia was unable to increase ER stress response marker mRNAs.

In summary, insulin resistance, either produced by lipid infusions in normal subjects or chronically present in T2DM patients, was associated with decreased hyperinsulinemia induced ER stress responses. This suggested, but did not prove, that these 2 phenomena were causally related.

  • Received January 13, 2014.
  • Accepted April 10, 2014.

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