Mitochondrial Dysfunction in Type 2 Diabetes and Obesity

Endocrinology and Metabolism Clinics of North America

Volumn 37, Issue 3, 2008, Pages 713-731

  Højlund, Kurt ^a   Mogensen, Martin ^b   Sahlin, Kent ^b,c   Beck Nielsen, Henning ^a  

^a ODENSE UNIVERSITY HOSPITAL   (Denmark)

^b UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^c SWEDISH SCHOOL OF SPORT AND HEALTH SCIENCES   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOGEN SYNTHASE; TRANSCRIPTOME;

ENZYME ACTIVATION; FUNCTIONAL PROTEOMICS; GENE; HUMAN; INSULIN RESISTANCE; MITOCHONDRIAL RESPIRATION; MUSCLE MITOCHONDRION; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; OXPHOS GENE; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; TISSUE SPECIFICITY;

BIOGENESIS; DIABETES MELLITUS, TYPE 2; HUMANS; INSULIN RESISTANCE; MITOCHONDRIA; OBESITY; OXIDATION-REDUCTION; PROTEOMICS;

EID: 50449084335     PISSN: 08898529     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ecl.2008.06.006     Document Type: Review

References (101)

1. Zimmet P., Alberti K.G., and Shaw J. Global and societal implications of the diabetes epidemic. Nature 414 (2001) 782-787
2. Beck-Nielsen H., Vaag A., Poulsen P., et al. Metabolic and genetic influence on glucose metabolism in type 2 diabetic subjects-experiences from relatives and twin studies. Best Pract Res Clin Endocrinol Metab 17 (2003) 445-467
3. Kahn S.E. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 46 (2003) 3-19
4. Shulman G.I., Rothman D.L., Jue T., et al. Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med 322 (1990) 223-228
5. Cusi K., Maezono K., Osman A., et al. Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. J Clin Invest 105 (2000) 311-320
6. Damsbo P., Vaag A., Hother-Nielsen O., et al. Reduced glycogen synthase activity in skeletal muscle from obese patients with and without type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 34 (1991) 239-245
7. Højlund K., Staehr P., Hansen B.F., et al. Increased phosphorylation of skeletal muscle glycogen synthase at NH2-terminal sites during physiological hyperinsulinemia in type 2 diabetes. Diabetes 52 (2003) 1393-1402
8. Højlund K., and Beck-Nielsen H. Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle. Markers or mediators of insulin resistance in type 2 diabetes. Curr Diabetes Rev 2 (2006) 375-95
9. Krook A., Bjornholm M., Galuska D., et al. Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients. Diabetes 49 (2000) 284-292
10. Bjornholm M., Kawano Y., Lehtihet M., et al. Insulin receptor substrate-1 phosphorylation and phosphatidylinositol 3-kinase activity in skeletal muscle from NIDDM subjects after in vivo insulin stimulation. Diabetes 46 (1997) 524-527
11. Højlund K., Frystyk J., Levin K., et al. Reduced plasma adiponectin concentrations may contribute to impaired insulin activation of glycogen synthase in skeletal muscle of patients with type 2 diabetes. Diabetologia 49 (2006) 1283-1291
12. Pratipanawatr T., Cusi K., Ngo P., et al. Normalization of plasma glucose concentration by insulin therapy improves insulin-stimulated glycogen synthesis in type 2 diabetes. Diabetes 51 (2002) 462-468
13. Kelley D.E., and Mandarino L.J. Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes 49 (2000) 677-683
14. Kelley D.E. Skeletal muscle fat oxidation: timing and flexibility are everything. J Clin Invest 115 (2005) 1699-1702
15. Simoneau J.A., Veerkamp J.H., Turcotte L.P., et al. Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss. FASEB J 13 (1999) 2051-2060
16. Kelley D.E., and Simoneau J.A. Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus. J Clin Invest 94 (1994) 2349-2356
17. Kelley D.E., Goodpaster B., Wing R.R., et al. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol 277 (1999) E1130-E1141
18. Pan D.A., Lillioja S., Kriketos A.D., et al. Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 46 (1997) 983-988
19. Phillips D.I., Caddy S., Ilic V., et al. Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects. Metabolism 45 (1996) 947-950
20. He J., Watkins S., and Kelley D.E. Skeletal muscle lipid content and oxidative enzyme activity in relation to muscle fiber type in type 2 diabetes and obesity. Diabetes 50 (2001) 817-823
21. Levin K., Daa Schroeder H., Alford F.P., et al. Morphometric documentation of abnormal intramyocellular fat storage and reduced glycogen in obese patients with type II diabetes. Diabetologia 44 (2001) 824-833
22. Krebs M., and Roden M. Molecular mechanisms of lipid-induced insulin resistance in muscle, liver and vasculature. Diabetes Obes Metab 7 (2005) 621-632
23. Adams II J.M., Pratipanawatr T., Berria R., et al. Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. Diabetes 53 (2004) 25-31
24. Lowell B.B., and Shulman G.I. Mitochondrial dysfunction and type 2 diabetes. Science 307 (2005) 384-387
25. Kruszynska Y.T., Mulford M.I., Baloga J., et al. Regulation of skeletal muscle hexokinase II by insulin in nondiabetic and NIDDM subjects. Diabetes 47 (1998) 1107-1113
26. Kelley D.E., He J., Menshikova E.V., et al. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51 (2002) 2944-2950
27. Kim J.Y., Hickner R.C., Cortright R.L., et al. Lipid oxidation is reduced in obese human skeletal muscle. Am J Physiol Endocrinol Metab 279 (2000) E1039-E1044
28. Simoneau J.A., and Kelley D.E. Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. J Appl Physiol 83 (1997) 166-171
29. Simoneau J.A., Colberg S.R., Thaete F.L., et al. Skeletal muscle glycolytic and oxidative enzyme capacities are determinants of insulin sensitivity and muscle composition in obese women. FASEB J 9 (1995) 273-278
30. Marin P., Andersson B., Krotkiewski M., et al. Muscle fiber composition and capillary density in women and men with NIDDM. Diabetes Care 17 (1994) 382-386
31. Lillioja S., Young A.A., Culter C.L., et al. Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man. J Clin Invest 80 (1987) 415-424
32. Oberbach A., Bossenz Y., Lehmann S., et al. Altered fiber distribution and fiber-specific glycolytic and oxidative enzyme activity in skeletal muscle of patients with type 2 diabetes. Diabetes Care 29 (2006) 895-900
33. Mogensen M., Sahlin K., Fernström M., et al. Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes. Diabetes 56 (2007) 1592-1599
34. Nyholm B., Qu Z., Kaal A., et al. Evidence of an increased number of type IIb muscle fibers in insulin-resistant first-degree relatives of patients with NIDDM. Diabetes 46 (1997) 1822-1828
35. østergård T., Jessen N., Schmitz O., et al. The effect of exercise, training, and inactivity on insulin sensitivity in diabetics and their relatives: what is new?. Appl Physiol Nutr Metab 32 (2007) 541-548
36. Nyholm B., Mengel A., Nielsen S., et al. Insulin resistance in relatives of NIDDM patients: the role of physical fitness and muscle metabolism. Diabetologia 39 (1996) 813-822
37. Thamer C., Stumvoll M., Niess A., et al. Reduced skeletal muscle oxygen uptake and reduced beta-cell function. Diabetes Care 26 (2003) 2126-2132
38. Orio Jr. F., Giallauria F., Palomba S., et al. Cardiopulmonary impairment in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 91 (2006) 2967-2971
39. Petersen K.F., Befroy D., Dufour S., et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300 (2003) 1140-1142
40. Barazonni R. Skeletal muscle mitochondrial protein metabolism and function in ageing and type 2 diabetes. Curr Opin Clin Nutr Metab Care 7 (2004) 97-102
41. Hood D.A., Irrcher I., Ljubicic V., et al. Coordination of metabolic plasticity in skeletal muscle. J Exp Biol 209 (2006) 2265-2275
42. Patti M.E., Butte A.J., Crunkhorn S., et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A 100 (2003) 8466-8471
43. Mootha V.K., Lindgren C.M., Eriksson K.F., et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34 (2003) 267-273
44. Sreekumar R., Halvatsiotis P., Schimke J.C., et al. Gene expression profile in skeletal muscle of type 2 diabetes and the effect of insulin treatment. Diabetes 51 (2002) 1913-1920
45. Yang X., Pratley R.E., Tokraks S., et al. Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians. Diabetologia 45 (2002) 1584-1593
46. Skov V., Glintborg D., Knudsen S., et al. Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome. Diabetes 56 (2007) 2349-2355
47. Wu Z., Puigserver P., Andersson U., et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98 (1999) 115-124
48. Subramanian A., Tamayo P., Mootha V.K., et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102 (2005) 15545-15550
49. Finck B.N., and Kelly D.P. PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 116 (2006) 615-622
50. Lin J., Handschin C., and Spiegelman B.M. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 1 (2005) 361-370
51. Timmons J.A., Norrbom J., Scheele C., et al. Expression profiling following local muscle inactivity in humans provides new perspective on diabetes-related genes. Genomics 87 (2006) 165-172
52. Ling C., Poulsen P., Carlsson E., et al. Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins. J Clin Invest 114 (2004) 1518-1526
53. Handschin C., and Spiegelman B.M. Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 27 (2006) 728-735
54. Jäger S., Handschin C., St-Pierre J., et al. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A 104 (2007) 12017-12022
55. Musi N., Fujii N., Hirshman M.F., et al. AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise. Diabetes 50 (2001) 921-927
56. Højlund K., Mustard K.J., Staehr P., et al. AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes. Am J Physiol Endocrinol Metab 286 (2004) E239-E244
57. Wojtaszewski J.F., Birk J.B., Frosig C., et al. 5'AMP activated protein kinase expression in human skeletal muscle: effects of strength training and type 2 diabetes. J Physiol 564 (2005) 563-573
58. Steinberg G.R., Smith A.C., Van Denderen B.J., et al. AMP-activated protein kinase is not down-regulated in human skeletal muscle of obese females. J Clin Endocrinol Metab 89 (2004) 4575-4580
59. Højlund K., Glintborg D., Andersen N.R., et al. Impaired insulin-stimulated phosphorylation of Akt and AS160 in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment. Diabetes (2007 Oct 31) [Epub ahead of print]
60. Højlund K., Wrzesinski K., Larsen P.M., et al. Proteome analysis reveals phosphorylation of ATP synthase beta-subunit in human skeletal muscle and proteins with potential roles in type 2 diabetes. J Biol Chem 278 (2003) 10436-10442
61. Arrell D.K., Elliott S.T., Kane L.A., et al. Proteomic analysis of pharmacological preconditioning: novel protein targets converge to mitochondrial metabolism pathways. Circ Res 99 (2006) 706-714
62. Bijur G.N., and Jope R.S. Rapid accumulation of Akt in mitochondria following phosphatidylinositol 3-kinase activation. J Neurochem 87 (2003) 1427-1435
63. Hopper R.K., Carroll S., Aponte A.M., et al. Mitochondrial matrix phosphoproteome: effect of extra mitochondrial calcium. Biochemistry 45 (2006) 2524-2536
64. Schulenberg B., Aggeler R., Beechem J.M., et al. Analysis of steady-state protein phosphorylation in mitochondria using a novel fluorescent phosphosensor dye. J Biol Chem 278 (2003) 27251-27255
65. Hittel D.S., Hathout Y., Hoffman E.P., et al. Proteome analysis of skeletal muscle from obese and morbidly obese women. Diabetes 54 (2005) 1283-1288
66. Ptitsyn A., Hulver M., Cefalu W., et al. Unsupervised clustering of gene expression data points at hypoxia as possible trigger for metabolic syndrome. BMC Genomics 7 (2006) 318
67. Gelfi C., De Palma S., Cerretelli P., et al. Two-dimensional protein map of human vastus lateralis muscle. Electrophoresis 24 (2003) 286-295
68. Højlund K., Yi Z., Hwang H., et al. Characterization of the human skeletal muscle proteome by one-dimensional gel electrophoresis and HPLC-ESI-MS/MS. Mol Cell Proteomics (2007 Oct 1) [Epub ahead of print]
69. Pagliarini D.J., and Dixon J.E. Mitochondrial modulation: reversible phosphorylation takes center stage?. Trends Biochem Sci 31 (2006) 26-34
70. Morino K., Petersen K.F., and Shulman G.I. Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes 55 Suppl 2 (2006) S9-S15
71. Petersen K.F., Dufour S., Befroy D., et al. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350 (2004) 664-671
72. Befroy D.E., Petersen K.F., Dufour S., et al. Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients. Diabetes 56 (2007) 1376-1381
73. Morino K., Petersen K.F., Dufour S., et al. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest 115 (2005) 3587-3593
74. Schrauwen-Hinderling V.B., Kooi M.E., Hesselink M.K., et al. Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects. Diabetologia 50 (2007) 113-120
75. Toledo F.G., Menshikova E.V., Ritov V.B., et al. Effects of physical activity and weight loss on skeletal muscle mitochondria and relationship with glucose control in type 2 diabetes. Diabetes 56 (2007) 2142-2147
76. Ritov V.B., Menshikova E.V., He J., et al. Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Diabetes 54 (2005) 8-14
77. Tonkonogi M., and Sahlin K. Rate of oxidative phosphorylation in isolated mitochondria from human skeletal muscle: effect of training status. Acta Physiol Scand 161 (1997) 345-353
78. Boushel R., Gnaiger E., Schjerling P., et al. Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia 50 (2007) 790-796
79. Ukropcova B., Sereda O., de Jonge L., et al. Family history of diabetes links impaired substrate switching and reduced mitochondrial content in skeletal muscle. Diabetes 56 (2007) 720-727
80. Wredenberg A., Freyer C., Sandström M.E., et al. Respiratory chain dysfunction in skeletal muscle does not cause insulin resistance. Biochem Biophys Res Commun 350 (2006) 202-207
81. Pospisilik J.A., Knauf C., Joza N., et al. Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes. Cell 131 (2007) 476-491
82. Short K.R., Nair K.S., and Stump C.S. Impaired mitochondrial activity and insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350 (2004) 2419-2421
83. Stump C.S., Short K.R., Bigelow M.L., et al. Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts. Proc Natl Acad Sci U S A 100 (2003) 7996-8001
84. Rome S., Clément K., Rabasa-Lhoret R., et al. Microarray profiling of human skeletal muscle reveals that insulin regulates ∼800 genes during a hyperinsulinemic clamp. J Biol Chem 278 (2003) 18063-18068
85. Petersen K.F., Dufour S., and Shulman G.I. Decreased insulin-stimulated ATP synthesis and phosphate transport in muscle of insulin-resistant offspring of type 2 diabetic parents. PLoS Med 2 (2005) e233
86. Szendroedi J., Schmid A.I., Chmelik M., et al. Muscle mitochondrial ATP synthesis and glucose transport/phosphorylation in type 2 diabetes. PLoS Med 4 (2007) e154
87. Brehm A., Krssak M., Schmid A.I., et al. Increased lipid availability impairs insulin-stimulated ATP synthesis in human skeletal muscle. Diabetes 55 (2006) 136-140
88. Hawley J.A., and Lessard S.J. Mitochondrial function: use it or lose it. Diabetologia 50 (2007) 699-702
89. Toledo F.G., Watkins S., and Kelley D.E. Changes induced by physical activity and weight loss in the morphology of intermyofibrillar mitochondria in obese men and women. J Clin Endocrinol Metab 91 (2006) 3224-3227
90. Burns N., Finucane F.M., Hatunic M., et al. Early-onset type 2 diabetes in obese white subjects is characterised by a marked defect in beta cell insulin secretion, severe insulin resistance and a lack of response to aerobic exercise training. Diabetologia 50 (2007) 1500-1508
91. Bogacka I., Xie H., Bray G.A., et al. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 54 (2005) 1392-1399
92. Mensink M., Hesselink M.K., Russell A.P., et al. Improved skeletal muscle oxidative enzyme activity and restoration of PGC-1 alpha and PPAR beta/delta gene expression upon rosiglitazone treatment in obese patients with type 2 diabetes mellitus. Int J Obes (Lond) 31 (2007) 1302-1310
93. Skov V., Glintborg D., Knudsen S., et al. Pioglitazone enhances mitochondrial biogenesis and ribosomal protein biosynthesis in skeletal muscle in polycystic ovary syndrome. PloS ONE 3 (2008) e2466
94. Civitarese A.E., Ukropcova B., Carling S., et al. Role of adiponectin in human skeletal muscle bioenergetics. Cell Metab 4 (2006) 75-87
95. Kadowaki T., and Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 26 (2005) 439-451
96. Bergeron R., Ren J.M., Cadman K.S., et al. Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis. Am J Physiol Endocrinol Metab 281 (2001) E1340-E1346
97. Zong H., Ren J.M., Young L.H., et al. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A 99 (2002) 15983-15987
98. Bandyopadhyay G.K., Yu J.G., Ofrecio J., et al. Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects. Diabetes 55 (2006) 2277-2285
99. Dahlman I., Forsgren M., Sjögren A., et al. Downregulation of electron transport chain genes in visceral adipose tissue in type 2 diabetes independent of obesity and possibly involving tumor necrosis factor-alpha. Diabetes 55 (2006) 1792-1799
100. Anello M., Lupi R., Spampinato D., et al. Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients. Diabetologia 48 (2005) 282-289
101. Misu H., Takamura T., Matsuzawa N., et al. Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes. Diabetologia 50 (2007) 268-277