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Mitochondrial oxidants, but not respiration, are sensitive to glucose in adipocytes

Thursday 2/20 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Heng Bai

Paper: Mitochondrial oxidants, but not respiration, are sensitive to
glucose in adipocytes

Authors: James R. Krycer, Sarah D. Elkington, Alexis Diaz-Vegas, Kristen C. Cooke, James G. Burchfield, Kelsey H. Fisher-Wellman, Gregory J. Cooney, Daniel J. Fazakerley, and David E. James

Insulin action in adipose tissue is crucial for whole-body glucose homeostasis, with insulin resistance being a major risk factor for metabolic diseases such as type 2 diabetes. Recent studies have proposed mitochondrial oxidants as a unifying driver of adipose insulin resistance, serving as a signal of nutrient excess. However, neither the substrates for nor sites of oxidant production are known. Because insulin stimulates glucose utilization, we hypothesized that glucose oxidation would fuel respiration, in turn generating mitochondrial oxidants. This would impair insulin action, limiting further glucose uptake in a negative feedback loop of “glucose-dependent” insulin resistance. Using primary rat adipocytes and cultured 3T3-L1 adipocytes, we observed that insulin increased respiration, but notably this occurred independently of glucose supply. In contrast, glucose was required for insulin to increase mitochondrial oxidants. Despite rising to similar levels as when treated with other agents that cause insulin resistance, glucose-dependent mitochondrial oxidants failed to cause insulin resistance. Subsequent studies revealed a temporal relationship whereby mitochondrial oxidants needed to increase before the insulin stimulus to induce insulin resistance. Together, these data reveal that (a) adipocyte respiration is principally fueled from nonglucose sources; (b) there is a disconnect between respiration and oxidative stress, whereby mitochondrial oxidant levels do not rise with increased respiration unless glucose is present; and (c) mitochondrial oxidative stress must precede the insulin stimulus to cause insulin

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Last Updated On Wednesday, January 29, 2020 by Orbell, Adam W
Created On Wednesday, January 29, 2020