Mitochondrial dysfunction and insulin resistance: an update

被引:380
作者
Montgomery, Magdalene K. [1 ]
Turner, Nigel [1 ]
机构
[1] Univ New South Wales, Sch Med Sci, UNSW Med, Dept Pharmacol, Sydney, NSW 2052, Australia
基金
澳大利亚研究理事会; 澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;
关键词
mitochondrial function; insulin resistance; lipid accumulation; oxidative stress; mitophagy; mitochondrial dynamics; HUMAN SKELETAL-MUSCLE; ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; OXYGEN SPECIES PRODUCTION; ACETYL-COA CARBOXYLASE-2; RESPIRATORY COMPLEX-I; WEIGHT-LOSS; ENERGY-EXPENDITURE; METABOLIC SYNDROME; NONDIABETIC SUBJECTS;
D O I
10.1530/EC-14-0092
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mitochondrial dysfunction has been implicated in the development of insulin resistance (IR); however, a large variety of association and intervention studies as well as genetic manipulations in rodents have reported contrasting results. Indeed, even 39 years after the first publication describing a relationship between IR and diminished mitochondrial function, it is still unclear whether a direct relationship exists, and more importantly if changes in mitochondrial capacity are a cause or consequence of IR. This review will take a journey through the past and summarise the debate about the occurrence of mitochondrial dysfunction and its possible role in causing decreased insulin action in obesity and type 2 diabetes. Evidence is presented from studies in various human populations, as well as rodents with genetic manipulations of pathways known to affect mitochondrial function and insulin action. Finally, we have discussed whether mitochondria are a potential target for the treatment of IR.
引用
收藏
页数:15
相关论文
共 139 条
  • [1] Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets
    Abu-Elheiga, L
    Oh, WK
    Kordari, P
    Wakil, SJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (18) : 10207 - 10212
  • [2] Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2
    Abu-Elheiga, L
    Matzuk, MM
    Abo-Hashema, KAH
    Wakil, SJ
    [J]. SCIENCE, 2001, 291 (5513) : 2613 - 2616
  • [3] Acetyl-CoA Carboxylase 2-/- Mutant Mice are Protected against Fatty Liver under High-fat, High-carbohydrate Dietary and de Novo Lipogenic Conditions
    Abu-Elheiga, Lutfi
    Wu, Hongmei
    Gu, Ziwei
    Bressler, Rubin
    Wakil, Salih J.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (15) : 12578 - 12588
  • [4] Mitochondrial uncoupling in skeletal muscle by UCP1 augments energy expenditure and glutathione content while mitigating ROS production
    Adjeitey, Cyril Nii-Klu
    Mailloux, Ryan J.
    deKemp, Robert A.
    Harper, Mary-Ellen
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2013, 305 (03): : E405 - E415
  • [5] Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans
    Anderson, Ethan J.
    Lustig, Mary E.
    Boyle, Kristen E.
    Woodlief, Tracey L.
    Kane, Daniel A.
    Lin, Chien-Te
    Price, Jesse W., III
    Kang, Li
    Rabinovitch, Peter S.
    Szeto, Hazel H.
    Houmard, Joseph A.
    Cortright, Ronald N.
    Wasserman, David H.
    Neufer, P. Darrell
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (03) : 573 - 581
  • [6] Derivatives of Rhodamine 19 as Mild Mitochondria-targeted Cationic Uncouplers
    Antonenko, Yuri N.
    Avetisyan, Armine V.
    Cherepanov, Dmitry A.
    Knorre, Dmitry A.
    Korshunova, Galina A.
    Markova, Olga V.
    Ojovan, Silvia M.
    Perevoshchikova, Irina V.
    Pustovidko, Antonina V.
    Rokitskaya, Tatyana I.
    Severina, Inna I.
    Simonyan, Ruben A.
    Smirnova, Ekaterina A.
    Sobko, Alexander A.
    Sumbatyan, Natalia V.
    Severin, Fedor F.
    Skulachev, Vladimir P.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (20) : 17831 - 17840
  • [7] RETRACTED: Vitamin D Supplementation Affects Serum High-Sensitivity C-Reactive Protein, Insulin Resistance, and Biomarkers of Oxidative Stress in Pregnant Women (Publication with Expression of Concern. See vol. 150, pg. 3042, 2020) (Retracted article. See vol. 151, pg. 1359, 2021)
    Asemi, Zatollah
    Samimi, Mansooreh
    Tabassi, Zohreh
    Shakeri, Hossein
    Esmailzadeh, Ahmad
    [J]. JOURNAL OF NUTRITION, 2013, 143 (09) : 1432 - 1438
  • [8] Skeletal muscle mitochondrial functions, mitochondrial DNA copy numbers, and gene transcript profiles in type 2 diabetic and nondiabetic subjects at equal levels of low or high insulin and euglycemia
    Asmann, Yan W.
    Stump, Craig S.
    Short, Kevin R.
    Coenen-Schimke, Jill M.
    Guo, ZengKui
    Bigelow, Maureen L.
    Nair, K. Sreekumaran
    [J]. DIABETES, 2006, 55 (12) : 3309 - 3319
  • [9] Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle -: Effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor α, and interleukin-6
    Bach, D
    Naon, D
    Pich, S
    Soriano, FX
    Vega, N
    Rieusset, J
    Laville, M
    Guillet, C
    Boirie, Y
    Wallberg-Henriksson, H
    Manco, M
    Calvani, M
    Castagneto, M
    Palacín, M
    Mingrone, G
    Zierath, JR
    Vidal, H
    Zorzano, A
    [J]. DIABETES, 2005, 54 (09) : 2685 - 2693
  • [10] Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism -: A novel regulatory mechanism altered in obesity
    Bach, D
    Pich, S
    Soriano, FX
    Vega, N
    Baumgartner, B
    Oriola, J
    Daugaard, JR
    Lloberas, J
    Camps, M
    Zierath, JR
    Rabasa-Lhoret, R
    Wallberg-Henriksson, H
    Laville, M
    Palacín, M
    Vidal, H
    Rivera, F
    Brand, M
    Zorzano, A
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (19) : 17190 - 17197