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Diabetologia
Published in: Diabetologia 4/2007

Open Access 01-04-2007 | Article

Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle

Authors: R. Boushel, E. Gnaiger, P. Schjerling, M. Skovbro, R. Kraunsøe, F. Dela

Published in: Diabetologia | Issue 4/2007

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Abstract

Aims/hypothesis

Insulin resistance and type 2 diabetes are associated with mitochondrial dysfunction. The aim of the present study was to test the hypothesis that oxidative phosphorylation and electron transport capacity are diminished in the skeletal muscle of type 2 diabetic subjects, as a result of a reduction in the mitochondrial content.

Materials and methods

The O2 flux capacity of permeabilised muscle fibres from biopsies of the quadriceps in healthy subjects (n = 8; age 58 ± 2 years [mean±SEM]; BMI 28 ± 1 kg/m2; fasting plasma glucose 5.4 ± 0.2 mmol/l) and patients with type 2 diabetes (n = 11; age 62 ± 2 years; BMI 32 ± 2 kg/m2; fasting plasma glucose 9.0 ± 0.8 mmol/l) was measured by high-resolution respirometry.

Results

O2 flux expressed per mg of muscle (fresh weight) during ADP-stimulated state 3 respiration was lower (p < 0.05) in patients with type 2 diabetes in the presence of complex I substrate (glutamate) (31 ± 2 vs 43 ± 3 pmol O2 s−1 mg−1) and in response to glutamate + succinate (parallel electron input from complexes I and II) (63 ± 3 vs 85 ± 6 pmol s−1 mg−1). Further increases in O2 flux capacity were observed in response to uncoupling by FCCP, but were again lower (p < 0.05) in type 2 diabetic patients than in healthy control subjects (86 ± 4 vs 109 ± 8 pmol s−1 mg−1). However, when O2 flux was normalised for mitochondrial DNA content or citrate synthase activity, there were no differences in oxidative phosphorylation or electron transport capacity between patients with type 2 diabetes and healthy control subjects.

Conclusions/interpretation

Mitochondrial function is normal in type 2 diabetes. Blunting of coupled and uncoupled respiration in type 2 diabetic patients can be attributed to lower mitochondrial content.
Literature
1.
Kelley DE, He J, Menshikova EV, Ritov VB (2002) Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51:2944–2950PubMed
2.
Vondra K, Rath R, Bass A, Slabochová Z, Teisinger T, Vítek V (1977) Enzyme activities in quadriceps femoris muscle of obese diabetic male patients. Diabetologia 13:527–529PubMedCrossRef
3.
He J, Watkins S, Kelley DE (2001) Skeletal muscle lipid content and oxidative enzyme activity in relation to muscle fiber type in type 2 diabetes and obesity. Diabetes 50:817–823PubMed
4.
Ørtenblad N, Mogensen M, Petersen I et al (2005) Reduced insulin-mediated citrate synthase activity in cultured skeletal muscle cells from patients with type 2 diabetes: evidence for an intrinsic oxidative enzyme defect. Biochim Biophys Acta 1741:206–214PubMed
5.
Simoneau JA, Kelley DE (1997) Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. J Appl Physiol 83:166–171PubMed
6.
Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI (2004) Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:664–671PubMedCrossRef
7.
Mootha VK, Lindgren CM, Eriksson KF et al (2003) PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34:267–273PubMedCrossRef
8.
Patti ME, Butte AJ, Crunkhorn S et al (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 100:8466–8471PubMedCrossRef
9.
Sparks LM, Xie H, Koza RA et al (2005) A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle. Diabetes 54:1926–1933PubMed
10.
Kuznetsov AV, Schneeberger S, Seiler R et al (2004) Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion. Am J Physiol Heart Circ Physiol 286:H1633–H1641PubMedCrossRef
11.
Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir Physiol 128:277–297PubMedCrossRef
12.
Andersen JL, Schjerling P, Andersen LL, Dela F (2003) Resistance training and insulin action in humans: effects of de-training. J Physiol 551:1049–1058PubMedCrossRef
13.
Morino K, Petersen KF, Dufour S et al (2005) Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest 115:3587–3593PubMedCrossRef
14.
Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625PubMed
15.
Scheede-Bergdahl C, Penkowa M, Hidalgo J et al (2005) Metallothionein-mediated antioxidant defense system and its response to exercise training are impaired in human type 2 diabetes. Diabetes 54:3089–3094PubMed
16.
Holloszy JO (1967) Biochemical adaptations in muscle. J Biol Chem 242:2278–2282PubMed
17.
Molé PA, Oscai LB, Holloszy JO (1971) Adaptation of muscle to exercise. Increase in levels of palmityl CoA synthetase, carnitine palmityltransferase, and palmityl CoA dehydrogenase, and in the capacity to oxidize fatty acids. J Clin Invest 50:2323–2330PubMedCrossRef
18.
Holloszy JO (1975) Adaptation of skeletal muscle to endurance exercise. Med Sci Sports 7:155–164PubMed
19.
Holloszy JO, Booth FW (1976) Biochemical adaptations to endurance exercise in muscle. Ann Rev Physiol 273–291
20.
Pilegaard H, Saltin B, Neufer PD (2003) Exercise induces transient transcriptional activation of the PGC-1α gene in human skeletal muscle. J Physiol 546:851–858PubMedCrossRef
21.
Short KR, Vittone JL, Bigelow ML et al (2003) Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity. Diabetes 52:1888–1896PubMed
22.
Pan XR, Li GW, Hu YH et al (1997) Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 20:537–544PubMed
23.
Knowler WC, Barrett-Connor E, Fowler SE et al (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403PubMedCrossRef
24.
Eriksson K-F, Lindgärde F (1991) Prevention of type 2 (non-insulin-dependent) diabetes mellitus by diet and physical exercise. Diabetologia 34:891–898PubMedCrossRef
25.
Tuomilehto J, Lindstrom J, Eriksson JG et al (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350PubMedCrossRef
26.
Dela F, Mikines KJ, Larsen JJ, Ploug T, Petersen LN, Galbo H (1995) Insulin-stimulated muscle glucose clearance in patients with NIDDM. Effects of one-legged physical training. Diabetes 44:1010–1020PubMed
27.
Holten MK, Zacho M, Gaster M, Juel C, Wojtaszewski JFP, Dela F (2004) Strength training increases insulin-mediated glucose uptake, GLUT4 content and insulin signaling in skeletal muscle in patients with Type 2 diabetes. Diabetes 53:294–305PubMed
28.
Dela F, Ploug T, Handberg A et al (1994) Physical training increases muscle GLUT-4 protein and mRNA in patients with NIDDM. Diabetes 43:862–865PubMed
29.
Wojtaszewski JF, Birk JB, Frosig C, Holten M, Pilegaard H, Dela F (2005) 5′AMP activated protein kinase expression in human skeletal muscle: effects of strength training and type 2 diabetes. J Physiol 564:563–573PubMedCrossRef
30.
Christ-Roberts CY, Pratipanawatr T, Pratipanawatr W et al (2004) Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signaling in overweight nondiabetic and type 2 diabetic subjects. Metabolism 53:1233–1242PubMedCrossRef
31.
Sriwijitkamol A, Christ-Roberts C, Berria R et al (2006) Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training. Diabetes 55:760–767PubMedCrossRef
32.
Toledo FG, Watkins S, Kelley DE (2006) Changes induced by physical activity and weight loss in the morphology of intermyofibrillar mitochondria in obese men and women. J Clin Endocrinol Metab 91:3224–3227PubMedCrossRef
33.
Coyle EF, Martin WH 3rd, Sinacore DR, Joyner MJ, Hagberg JM, Holloszy JO (1984) Time course of loss of adaptations after stopping prolonged intense endurance training. J Appl Physiol 57:1857–1864PubMed
34.
Booth FW, Holloszy JO (1977) Cytochrome c turnover in rat skeletal muscles. J Biol Chem 252:416–419PubMed
35.
Henriksson J, Reitman JS (1977) Time course of changes in human skeletal muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with physical activity and inactivity. Acta Physiol Scand 99:91–97PubMedCrossRef
36.
Bjorntorp P, Schersten T, Fagerberg SE (1967) Respiration and phosphorylation of mitochondria isolated from the skeletal muscle of diabetic and normal subjects. Diabetologia 3:346–352PubMedCrossRef
Metadata
Title
Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle
Authors
R. Boushel
E. Gnaiger
P. Schjerling
M. Skovbro
R. Kraunsøe
F. Dela
Publication date
01-04-2007
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 4/2007
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-007-0594-3

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