Boushel 2007 Diabetologia

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Publications in the MiPMap
Boushel RC, Gnaiger E, Schjerling P, Skovbro M, Kraunsoee R, Dela F (2007) Patients with Type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia 50:790-6.

» PMID: 17334651 Open Access

Boushel RC, Gnaiger E, Schjerling P, Skovbro M, Kraunsoee R, Dela F (2007) Diabetologia

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.

Keywords: Diabetes, Mitochondria, Skeletal muscle Bioblast editor: Gnaiger E O2k-Network Lab: DK Copenhagen Dela F, AT Innsbruck Gnaiger E, SE Stockholm Boushel RC, CA Vancouver Boushel RC, DK Copenhagen Larsen S

SUIT-011

SUIT protocol

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Corrections

Some concentrations of substrates applied in the respirometric protocols are reported in this publication to have been higher than in MiPNet09.12, but actually the concentrations have been applied according to MiPNet09.12.



MitoEAGLE VO2max/BME database

  • Human vastus lateralis
  • 8 males
  • 58 years
  • Western sedentary lifestyle, routine activities (walking, gardening..), not engaged in regular structured aerobic or strength training programmes or athletics; non-diabetic controls
  • H = 1.79 m
  • M = 90 kg
  • BME = 0.34
  • BMI = 28.1 kg·m-2
  • VO2max/M = 31.2 mL·min-1·kg-1
  • Permeabilized muscle fibres; 37 °C; GMSP; mw
  • JO2,P(NS) = 85.4 µmol·s-1·kg-1 wet muscle mass

  • Human vastus lateralis
  • 11 males
  • 62 years
  • T2 Diabetic patients
  • H = 1.77 m
  • M = 100.5 kg
  • BME = 0.55
  • BMI = 32.1 kg·m-2
  • VO2max/M
  • Permeabilized muscle fibres; 37 °C; GMSP; mw
  • JO2,P(NS) = 63.5 µmol·s-1·kg-1 wet muscle mass

References: BME and VO2max

» VO2max
 Reference
Bakkman 2007 ActaPhysiolBakkman L, Sahlin K, Holmberg HC, Tonkonogi M (2007) Quantitative and qualitative adaptation of human skeletal muscle mitochondria to hypoxic compared with normoxic training at the same relative work rate. Acta Physiol (Oxford) 190:243–51.
Boushel 2007 DiabetologiaBoushel RC, Gnaiger E, Schjerling P, Skovbro M, Kraunsoee R, Dela F (2007) Patients with Type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia 50:790-6.
Chambers 2020 J Appl Physiol (1985)Chambers TL, Burnett TR, Raue U, Lee GA, Finch WH, Graham BM, Trappe TA, Trappe S (2020) Skeletal muscle size, function, and adiposity with lifelong aerobic exercise. J Appl Physiol (1985) 128:368–78.
Daussin 2008 Am J Physiol Regul Integr Comp PhysiolDaussin FN, Zoll J, Dufour SP, Ponsot E, Lonsdorfer-Wolf E, Doutreleau S, Mettauer B, Piquard F, Geny B, Richard R (2008) Effect of interval versus continuous training on cardiorespiratory and mitochondrial functions: relationship to aerobic performance improvements in sedentary subjects. Am J Physiol Regul Integr Comp Physiol 295:R264-72.
Garnier 2005 FASEB JGarnier A, Fortin D, Zoll J, N'Guessan B, Mettauer B, Lampert E, Veksler V, Ventura-Clapier R (2005) Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle. FASEB J 19:43-52.
Gnaiger 2015 Scand J Med Sci SportsGnaiger E, Boushel R, Søndergaard H, Munch-Andersen T, Damsgaard R, Hagen C, Díez-Sánchez C, Ara I, Wright-Paradis C, Schrauwen P, Hesselink M, Calbet JAL, Christiansen M, Helge JW, Saltin B (2015) Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and caucasians in the arctic winter. Scand J Med Sci Sports 25 (Suppl 4):126–34.
Gnaiger 2019 MiP2019
Erich Gnaiger
OXPHOS capacity in human muscle tissue and body mass excess – the MitoEAGLE mission towards an integrative database (Version 6; 2020-01-12).
Loe 2013 PLOS ONELoe H, Rognmo Ø, Saltin B, Wisløff U (2013) Aerobic capacity reference data in 3816 healthy men and women 20-90 years. PLOS ONE 8:e64319.
Mettauer 2001 J Am Coll CardiolMettauer B, Zoll J, Sanchez H, Lampert E, Ribera F, Veksler V, Bigard X, Mateo P, Epailly E, Lonsdorfer J, Ventura-Clapier R (2001) Oxidative capacity of skeletal muscle in heart failure patients versus sedentary or active control subjects. J Am Coll Cardiol 38:947-54.
Mogensen 2006 J PhysiolMogensen M, Bagger M, Pedersen PK, Fernström M, Sahlin K (2006) Cycling efficiency in humans is related to low UCP3 content and to type I fibres but not to mitochondrial efficiency. J Physiol 571:669-81.
N'Guessan 2004 Mol Cell BiochemN'Guessan B, Zoll J, Ribera F, Ponsot E, Lampert E, Ventura-Clapier R, Veksler V, Mettauer B (2004) Evaluation of quantitative and qualitative aspects of mitochondrial function in human skeletal and cardiac muscles. Mol Cell Biochem 256-257:267-80.
Pesta 2011 Am J Physiol Regul Integr Comp PhysiolPesta D, Hoppel F, Macek C, Messner H, Faulhaber M, Kobel C, Parson W, Burtscher M, Schocke M, Gnaiger E (2011) Similar qualitative and quantitative changes of mitochondrial respiration following strength and endurance training in normoxia and hypoxia in sedentary humans. Am J Physiol Regul Integr Comp Physiol 301:R1078–87.
Ponsot 2006 J Appl Physiol (1985)Ponsot E, Dufour SP, Zoll J, Doutrelau S, N'Guessan B, Geny B, Hoppeler H, Lampert E, Mettauer B, Ventura-Clapier R, Richard R (2006) Exercise training in normobaric hypoxia in endurance runners. II. Improvement of mitochondrial properties in skeletal muscle. J Appl Physiol (1985) 100:1249-57.
Pribis 2010 NutrientsPribis P, Burtnack CA, McKenzie SO, Thayer J (2010) Trends in body fat, body mass index and physical fitness among male and female college students. Nutrients 2:1075-85.
Raboel 2009 Diabetes Obes MetabRaboel R, Hojberg PM, Almdal T, Boushel RC, Haugaard SB, Madsbad S, Dela F (2009) Improved glycaemic control decreases inner mitochondrial membrane leak in type 2 diabetes. Diabetes Obes Metab 11:355-60.
Rasmussen 2001 Am J Physiol Endocrinol MetabRasmussen 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:E301-7.
Rasmussen 2003 Eur J PhysiolRasmussen UF, Krustrup P, Kjaer M, Rasmussen HN (2003) Human skeletal muscle mitochondrial metabolism in youth and senescence: no signs of functional changes in ATP formation and mitochondrial oxidative capacity. Pflugers Arch – Eur J Physiol 446:270-78.
Zoll 2002 J PhysiolZoll J, Sanchez H, N'Guessan B, Ribera F, Lampert E, Bigard X, Surrurier B, Fortin D, Geny B, Veksler V, Ventura-Clapier R, Mettauer B (2002) Physical activity changes the regulation of mitochondrial respiration in human skeletal muscle. J Physiol 543:191-200.

MitoPedia: BME and mitObesity

» Body mass excess and mitObesity | BME and mitObesity news | Summary |

TermAbbreviationDescription
BME cutoff pointsBME cutoffObesity is defined as a disease associated with an excess of body fat with respect to a healthy reference condition. Cutoff points for body mass excess, BME cutoff points, define the critical values for underweight (-0.1 and -0.2), overweight (0.2), and various degrees of obesity (0.4, 0.6, 0.8, and above). BME cutoffs are calibrated by crossover-points of BME with established BMI cutoffs.
Body fat excessBFEIn the healthy reference population (HRP), there is zero body fat excess, BFE, and the fraction of excess body fat in the HRP is expressed - by definition - relative to the reference body mass, M°, at any given height. Importantly, body fat excess, BFE, and body mass excess, BME, are linearly related, which is not the case for the body mass index, BMI.
Body massm [kg]; M [kg·x-1]The body mass, M, is the mass (kilogram [kg]) of an individual (object) [x] and is expressed in units [kg/x]. Whereas the body weight changes as a function of gravitational force (you are weightless at zero gravity; your floating weight in water is different from your weight in air), your mass is independent of gravitational force, and it is the same in air and water.
Body mass excessBMEThe body mass excess, BME, is an index of obesity and as such BME is a lifestyle metric. The BME is a measure of the extent to which your actual body mass, M [kg/x], deviates from M° [kg/x], which is the reference body mass [kg] per individual [x] without excess body fat in the healthy reference population, HRP. A balanced BME is BME° = 0.0 with a band width of -0.1 towards underweight and +0.2 towards overweight. The BME is linearly related to the body fat excess.
Body mass indexBMIThe body mass index, BMI, is the ratio of body mass to height squared (BMI=M·H-2), recommended by the WHO as a general indicator of underweight (BMI<18.5 kg·m-2), overweight (BMI>25 kg·m-2) and obesity (BMI>30 kg·m-2). Keys et al (1972; see 2014) emphasized that 'the prime criterion must be the relative independence of the index from height'. It is exactly the dependence of the BMI on height - from children to adults, women to men, Caucasians to Asians -, which requires adjustments of BMI-cutoff points. This deficiency is resolved by the body mass excess relative to the healthy reference population.
ComorbidityComorbidities are common in obesogenic lifestyle-induced early aging. These are preventable, non-communicable diseases with strong associations to obesity. In many studies, cause and effect in the sequence of onset of comorbidities remain elusive. Chronic degenerative diseases are commonly obesity-induced. The search for the link between obesity and the etiology of diverse preventable diseases lead to the hypothesis, that mitochondrial dysfunction is the common mechanism, summarized in the term 'mitObesity'.
Healthy reference populationHRPA healthy reference population, HRP, establishes the baseline for the relation between body mass and height in healthy people of zero underweight or overweight, providing a reference for evaluation of deviations towards underweight or overweight and obesity. The WHO Child Growth Standards (WHO-CGS) on height and body mass refer to healthy girls and boys from Brazil, Ghana, India, Norway, Oman and the USA. The Committee on Biological Handbooks compiled data on height and body mass of healthy males from infancy to old age (USA), published before emergence of the fast-food and soft-drink epidemic. Four allometric phases are distinguished with distinct allometric exponents. At heights above 1.26 m/x the allometric exponent is 2.9, equal in women and men, and significantly different from the exponent of 2.0 implicated in the body mass index, BMI [kg/m2].
Height of humansh [m]; H [m·x-1]The height of humans, h, is given in SI units in meters [m]. Humans are countable objects, and the symbol and unit of the number of objects is N [x]. The average height of N objects is, H = h/N [m/x], where h is the heights of all N objects measured on top of each other. Therefore, the height per human has the unit [m·x-1] (compare body mass [kg·x-1]). Without further identifyer, H is considered as the standing height of a human, measured without shoes, hair ornaments and heavy outer garments.
Lengthl [m]Length l is an SI base quantity with SI base unit meter m. Quantities derived from length are area A [m2] and volume V [m3]. Length is an extensive quantity, increasing additively with the number of objects. The term 'height' h is used for length in cases of vertical position (see height of humans). Length of height per object, LUX [m·x-1] is length per unit-entity UX, in contrast to lentgth of a system, which may contain one or many entities, such as the length of a pipeline assembled from a number NX of individual pipes. Length is a quantity linked to direct sensory, practical experience, as reflected in terms related to length: long/short (height: tall/small). Terms such as 'long/short distance' are then used by analogy in the context of the more abstract quantity time (long/short duration).
MitObesity drugsBioactive mitObesity compounds are drugs and nutraceuticals with more or less reproducible beneficial effects in the treatment of diverse preventable degenerative diseases implicated in comorbidities linked to obesity, characterized by common mechanisms of action targeting mitochondria.
ObesityObesity is a disease resulting from excessive accumulation of body fat. In common obesity (non-syndromic obesity) excessive body fat is due to an obesogenic lifestyle with lack of physical exercise ('couch') and caloric surplus of food consumption ('potato'), causing several comorbidities which are characterized as preventable non-communicable diseases. Persistent body fat excess associated with deficits of physical activity induces a weight-lifting effect on increasing muscle mass with decreasing mitochondrial capacity. Body fat excess, therefore, correlates with body mass excess up to a critical stage of obesogenic lifestyle-induced sarcopenia, when loss of muscle mass results in further deterioration of physical performance particularly at older age.
VO2maxVO2max; VO2max/MMaximum oxygen consumption, VO2max, is and index of cardiorespiratory fitness, measured by spiroergometry on human and animal organisms capable of controlled physical exercise performance on a treadmill or cycle ergometer. VO2max is the maximum respiration of an organism, expressed as the volume of O2 at STPD consumed per unit of time per individual object [mL.min-1.x-1]. If normalized per body mass of the individual object, M [kg.x-1], mass specific maximum oxygen consumption, VO2max/M, is expressed in units [mL.min-1.kg-1].


Labels: MiParea: Respiration, mt-Biogenesis;mt-density, mt-Medicine  Pathology: Diabetes, Obesity 

Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Regulation: Coupling efficiency;uncoupling, Substrate  Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS  HRR: Oxygraph-2k 

SUIT-011, BMI, VO2max, BME, MitoEAGLE BME