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Mitochondrial dysfunction has divergent, cell type-dependent effects on insulin action

Martin,SD, Morrison,S, Konstantopoulos,N and McGee,SL 2014, Mitochondrial dysfunction has divergent, cell type-dependent effects on insulin action, Molecular metabolism, vol. 3, no. 4, pp. 408-418, doi: 10.1016/j.molmet.2014.02.001.

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Title Mitochondrial dysfunction has divergent, cell type-dependent effects on insulin action
Author(s) Martin,SD
Morrison,S
Konstantopoulos,N
McGee,SL
Journal name Molecular metabolism
Volume number 3
Issue number 4
Start page 408
End page 418
Publisher Elsevier BV
Place of publication Amsterdam, Netherlands
Publication date 2014-07
ISSN 2212-8778
Keyword(s) AMPK, AMP-activated protein kinase
AS160, Akt substrate of 160 kDa
Adipocyte
BSA, bovine serum albumin
ECAR, extracellular acidification rate
FoxO1, forkhead box protein O1
G.O., glucose oxidase
GLUT4, facilitative glucose transporter isoform 4
GP, glucose production
HI-FBS, heat-inactivated foetal bovine serum
Hepatocyte
IRS1, insulin receptor substrate 1
Insulin action
LDH, lactate dehydrogenase
MMP, mitochondrial membrane potential
Mitochondria
MnTBAP, manganese (III) tetrakis (4-benzoic acid) porphyrin chloride
PI3K, phosphatidylinositol 3-kinase
ROS, reactive oxygen species
Reactive oxygen species
SOD, superoxide dismutase
T2D, type 2 diabetes
TNFα, tumour necrosis factor alpha
Summary The contribution of mitochondrial dysfunction to insulin resistance is a contentious issue in metabolic research. Recent evidence implicates mitochondrial dysfunction as contributing to multiple forms of insulin resistance. However, some models of mitochondrial dysfunction fail to induce insulin resistance, suggesting greater complexity describes mitochondrial regulation of insulin action. We report that mitochondrial dysfunction is not necessary for cellular models of insulin resistance. However, impairment of mitochondrial function is sufficient for insulin resistance in a cell type-dependent manner, with impaired mitochondrial function inducing insulin resistance in adipocytes, but having no effect, or insulin sensitising effects in hepatocytes. The mechanism of mitochondrial impairment was important in determining the impact on insulin action, but was independent of mitochondrial ROS production. These data can account for opposing findings on this issue and highlight the complexity of mitochondrial regulation of cell type-specific insulin action, which is not described by current reductionist paradigms.
Language eng
DOI 10.1016/j.molmet.2014.02.001
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 920104 Diabetes
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, Elsevier
Persistent URL http://hdl.handle.net/10536/DRO/DU:30067301

Document type: Journal Article
Collection: School of Medicine
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Created: Mon, 08 Dec 2014, 14:27:15 EST

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