Abstract
Background: Skeletal muscle mitochondrial function in type 2 diabetes (T2D) is currently being studied intensively. In vivo 31P magnetic resonance spectroscopy (31P MRS) is a noninvasive tool used to measure mitochondrial respiratory function (MIFU) in skeletal muscle tissue. However, microvascular co-morbidity in long-standing T2D can interfere with the 31P MRS methodology.
Aim: To compare 31P MRS-derived parameters describing in vivo MIFU with an in vitro assessment of muscle respiratory capacity and muscle fiber-type composition in T2D patients.
Methods: 31P MRS was applied in long-standing, insulin-treated T2D patients. 31P MRS markers of MIFU were measured in the M. vastus lateralis. Muscle biopsy samples were collected from the same muscle and analyzed for succinate dehydrogenase activity (SDH) and fiber-type distribution.
Results: Several 31P MRS parameters of MIFU showed moderate to good correlations with the percentage of type I fibers and type I fiber-specific SDH activity (Pearson’s R between 0.70 and 0.75). In vivo and in vitro parameters of local mitochondrial respiration also correlated well with whole-body fitness levels (VO 2peak) in these patients (Pearson’s R between 0.62 and 0.90).
Conclusion: Good correlations exist between in vivo and in vitro measurements of MIFU in long-standing insulin-treated T2D subjects, which are qualitatively and quantitatively consistent with previous results measured in healthy subjects. This justifies the use of 31P MRS to measure MIFU in relation to T2D.
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References
Lowell BB, Shulman GI (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307:384–387
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 350:664–671
Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300:1140–1142
Kelley DE, He J, Menshikova EV, Ritov VB (2002) Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51:2944–2950
Short KR, Nair KS, Stump CS (2004) Impaired mitochondrial activity and insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:2419–2421; author reply 2419–2421
Simoneau JA, Kelley DE (1997) Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. J Appl Physiol 83:166–171
van Loon LJ, Goodpaster BH (2006) Increased intramuscular lipid storage in the insulin-resistant and endurance-trained state. Pflugers Arch 451:606–616
Arnold DL, Matthews PM, Radda GK (1984) Metabolic recovery after exercise and the assessment of mitochondrial function in vivo in human skeletal muscle by means of 31P NMR. Magn Reson Med 1:307–315
Mattei JP, Bendahan D, Cozzone P (2004) P-31 magnetic resonance spectroscopy. A tool for diagnostic purposes and pathophysiological insights in muscle diseases. Reumatismo 56:9–14
Radda GK, Odoom J, Kemp G, Taylor DJ, Thompson C, Styles P (1995) Assessment of mitochondrial function and control in normal and diseased states. Biochim Biophys Acta 1271:15–19
Kemp GJ, Taylor DJ, Thompson CH, Hands LJ, Rajagopalan B, Styles P, Radda GK (1993) Quantitative analysis by 31P magnetic resonance spectroscopy of abnormal mitochondrial oxidation in skeletal muscle during recovery from exercise. NMR Biomed 6:302–310
Radda GK, Kemp GJ, Styles P, Taylor DJ (1993) Control of oxidative phosphorylation in muscle. Biochem Soc Trans 21(Pt 3):762–764
Arnold DL, Taylor DJ, Radda GK (1985) Investigation of human mitochondrial myopathies by phosphorus magnetic resonance spectroscopy. Ann Neurol 18:189–196
Kemp GJ, Radda GK (1994) Quantitative interpretation of bioenergetic data from 31P and 1H magnetic resonance spectroscopic studies of skeletal muscle: an analytical review. Magn Reson Q 10:43–63
Larson-Meyer DE, Newcomer BR, Hunter GR, Joanisse DR, Weinsier RL, Bamman MM (2001) Relation between in vivo and in vitro measurements of skeletal muscle oxidative metabolism. Muscle Nerve 24:1665–1676
McCully KK, Fielding RA, Evans WJ, Leigh JS, Jr, Posner JD (1993) Relationships between in vivo and in vitro measurements of metabolism in young and old human calf muscles. J Appl Physiol 75:813–819
Argov Z, De Stefano N, Taivassalo T, Chen J, Karpati G, Arnold DL (1997) Abnormal oxidative metabolism in exercise intolerance of undetermined origin. Neuromuscul Disord 7:99–104
Bendahan D, Desnuelle C, Vanuxem D, Confort-Gouny S, Figarella-Branger D, Pellissier JF, Kozak-Ribbens G, Pouget J, Serratrice G, Cozzone PJ (1992) 31P NMR spectroscopy and ergometer exercise test as evidence for muscle oxidative performance improvement with coenzyme Q in mitochondrial myopathies. Neurology 42: 1203–1208
Massie BM, Conway M, Yonge R, Frostick S, Sleight P, Ledingham J, Radda G, Rajagopalan B (1987) 31P nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with congestive heart failure. Am J Cardiol 60:309–315
Pipinos II, Shepard AD, Anagnostopoulos PV, Katsamouris, A, Boska MD (2000) Phosphorus 31 nuclear magnetic resonance spectroscopy suggests a mitochondrial defect in claudicating skeletal muscle. J Vasc Surg 31:944–952
Bendahan D, Confort-Gouny S, Kozak-Reiss G, Cozzone PJ (1990) Heterogeneity of metabolic response to muscular exercise in humans. New criteria of invariance defined by in vivo phosphorus-31 NMR spectroscopy. FEBS Lett 272:155–158
Iotti S, Lodi R, Frassineti C, Zaniol P, Barbiroli B (1993) In vivo assessment of mitochondrial functionality in human gastrocnemius muscle by 31P MRS The role of pH in the evaluation of phosphocreatine and inorganic phosphate recoveries from exercise. NMR Biomed 6:248–253
Lodi R, Kemp GJ, Iotti S, Radda GK, Barbiroli B (1997) Influence of cytosolic pH on in vivo assessment of human muscle mitochondrial respiration by phosphorus magnetic resonance spectroscopy. Magn Reson Mator Phy. 5:165–171
Roussel M, Bendahan D, Mattei JP, Le Fur Y, Cozzone PJ (2000) 31P magnetic resonance spectroscopy study of phosphocreatine recovery kinetics in skeletal muscle: the issue of intersubject variability. Biochim Biophys Acta 1457:18–26
Quistorff B, Johansen L, Sahlin K (1993) Absence of phosphocreatine resynthesis in human calf muscle during ischaemic recovery. Biochem J 291(Pt 3):681–686
Haseler LJ, Lin AP, Richardson RS (2004) Skeletal muscle oxidative metabolism in sedentary humans: 31P-MRS assessment of O2 supply and demand limitations. J Appl Physiol 97:1077–1081
Home P (2005) Contributions of basal and post-prandial hyperglycaemia to micro- and macrovascular complications in people with type 2 diabetes. Curr Med Res Opin 21:989–998
Young JL, Pendergast DR, Steinbach J (1991) Oxygen transport and peripheral microcirculation in long-term diabetes. Proc Soc Exp Biol Med 196:61–68
Marin P, Anersson B, Krotkiewski M, Bjorntorp P (1994) Muscle fiber composition and capillary density in women and men with NIDDM. Diabetes Care 17:382–386
Girach A, Vignati L (2006) Diabetic microvascular complications–can the presence of one predict the development of another? J Diabetes Complicat 20:228–237
Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553
Zhang YY, Johnson MC, 2nd, Chow N, Wasserman K (1991) Effect of exercise testing protocol on parameters of aerobic function. Med Sci Sports Exerc 23:625–630
Weber CT, Janicki JS, McElroy PA (1986) Cardiopulmonary exercise testing (CPX) testing. W.B. Saunders, Philadelphia
Richardson RS, Frank LR, Haseler LJ (1998) Dynamic knee-extensor and cycle exercise: functional MRI of muscular activity. Int J Sports Med 19:182–187
Vanhamme L, van den Boogaart A, Van Huffel S (1997) Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. J Magn Reson 129:35–43
Taylor DJ, Styles P, Matthews PM, Arnold DA, Gadian DG, Bore P, Radda GK (1986) Energetics of human muscle: exercise-induced ATP depletion. Magn Reson Med 3:44–54
Taylor DJ, Bore PJ, Styles P, Gadian DG, Radda GK (1983) Bioenergetics of intact human muscle. A 31P nuclear magnetic resonance study. Mol Biol Med 1:77–94
Lawson JW, Veech RL (1979) Effects of pH and free Mg2+ on the K eq of the creatine kinase reaction and other phosphate hydrolyses and phosphate transfer reactions. J Biol Chem 254:6528–6537
Boska M (1994) ATP production rates as a function of force level in the human gastrocnemius/soleus using 31P MRS. Magn Reson Med 32:1–10
Kemp GJ, Thompson CH, Barnes PR, Radda GK (1994) Comparisons of ATP turnover in human muscle during ischemic and aerobic exercise using 31P magnetic resonance spectroscopy. Magn Reson Med 31:248–258
Cho M, Webster SG, Blau HM (1993) Evidence for myoblast-extrinsic regulation of slow myosin heavy chain expression during muscle fiber formation in embryonic development. J Cell Biol 121:795–810
Gosker HR, van Mameren H, van Dijk PJ, Engelen MP, van der Vusse GJ, Wouters EF, Schols AM (2002) Skeletal muscle fibre-type shifting and metabolic profile in patients with chronic obstructive pulmonary disease. Eur Respir J 19:617–625
Argov Z, De Stefano N, Arnold DL (1996) ADP recovery after a brief ischemic exercise in normal and diseased human muscle—a 31P MRS study. NMR Biomed 9:165–172
Richardson RS (1998) Oxygen transport: air to muscle cell. Med Sci Sports Exerc 30:53–59
Kingwell BA, Formosa M, Muhlmann M, Bradley SJ, McConell GK (2003) Type 2 diabetic individuals have impaired leg blood flow responses to exercise: role of endothelium-dependent vasodilation. Diabetes Care 26:899–904
Rasmussen UF, Rasmussen HN, Krustrup P, Quistorff B, Saltin B, Bangsbo J (2001) Aerobic metabolism of human quadriceps muscle: in vivo data parallel measurements on isolated mitochondria. Am J Physiol Endocrinol Metab 280: E301–307
Scheuermann-Freestone M, Madsen PL, Manners D, Blamire AM, Buckingham RE, Styles P, Radda GK, Neubauer S, Clarke K (2003) Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes. Circulation 107:3040–3046
Kent-Braun JA, Ng AV (2000) Skeletal muscle oxidative capacity in young and older women and men. J Appl Physiol 89:1072–1078
Conley KE, Jubrias SA, Esselman PC (2000) Oxidative capacity and ageing in human muscle. J Physiol 526 (Pt 1):203–210
Schunk K, Pitton M, Duber C, Kersjes W, Schadmand-Fischer S, Thelen M (1999) Dynamic phosphorus-31 magnetic resonance spectroscopy of the quadriceps muscle: effects of age and sex on spectroscopic results. Invest Radiol 34:116–125
Giudicelli JF, Richer C, Richard C, Thuillez C (1991) Angiotensin converting enzyme inhibition. Systemic and regional hemodynamics in rats and humans. Am J Hypertens 4:258S–262S
Scheen AJ (2004) Renin-angiotensin system inhibition prevents type 2 diabetes mellitus Part 2. Overview of physiological and biochemical mechanisms. Diabetes Metab 30:498–505
Bahi L, Koulmann N, Sanchez H, Momken I, Veksler V, Bigard AX, Ventura-Clapier R (2004) Does ACE inhibition enhance endurance performance and muscle energy metabolism in rats?. J Appl Physiol 96:59–64
Challiss RA, Hayes DJ, Radda GK (1988) A 31P-NMR study of the acute effects of altered beta-adrenoceptor stimulation on the bioenergetics of skeletal muscle during contraction. Biochem Pharmacol 37:4653–4659
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Praet, S.F.E., Feyter, H.M.M.D., Jonkers, R.A.M. et al. 31P MR spectroscopy and in vitro markers of oxidative capacity in type 2 diabetes patients. Magn Reson Mater Phy 19, 321–331 (2006). https://doi.org/10.1007/s10334-006-0060-0
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DOI: https://doi.org/10.1007/s10334-006-0060-0