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Journal of Inherited Metabolic Disease

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01.12.2009 | REVIEW

Mitochondria and diabetes mellitus: untangling a conflictive relationship?

verfasst von: M. Schiff, S. Loublier, A. Coulibaly, P. Bénit, H. Ogier de Baulny, P. Rustin

Erschienen in: Journal of Inherited Metabolic Disease | Ausgabe 6/2009

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Summary

Diabetes mellitus is occasionally observed in patients with skeletal muscle respiratory chain deficiency, suggesting that skeletal muscle mitochondrial dysfunction might play a pathogenic role in type 2 diabetes (T2D). In support of this hypothesis, decreased muscle mitochondrial activity has been reported in T2D patients and in mouse models of diabetes. However, recent work by several groups suggests that decreased muscle mitochondrial function may be a consequence rather than a cause of diabetes, since decreased mitochondrial function in mice affords protection from diabetes and obesity. We review the data on this controversial but important issue of potential links between mitochondrial dysfunction and diabetes.

Affourtit C, Brand MD (2008) On the role of uncoupling protein--2 in pancreatic beta cells. Biochim Biophys Acta 1777:973–979PubMedCrossRef

Ashcroft E, Ashcroft S (1992) In: Ashcroft E, Ashcroft S (eds). Insulin: Molecular biology to pathology. OUP, Oxford, pp 97–150

Asmann YW, Stump CS, Short KR et al (2006) 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. Diabetes 55:3309–3319PubMedCrossRef

Ballinger SW, Shoffner JM, Hedaya EV et al (1992) Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion. Nat Genet 1:11–15PubMedCrossRef

Ballinger SW, Shoffner JM, Gebhart S, Koontz DA, Wallace DC (1994) Mitochondrial diabetes revisited. Nat Genet 7:458–459PubMedCrossRef

Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM (1993) Type 2 (non--insulin--dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 36:62–67PubMedCrossRef

Bénit P, Goncalves S, Dassa EP, Brière JJ, Rustin P (2008) The variability of the Harlequin mouse phenotype resembles that of human mitochondrial--complex I--deficiency syndromes. PloS One 3:e3208PubMedPubMedCentralCrossRef

Bonnard C, Durand A, Peyrol S et al (2008) Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet--induced insulin--resistant mice. J Clin Invest 118:789–800PubMedPubMedCentral

Boubaker K, Flepp M, Sudre P et al (2001) Hyperlactatemia and antiretroviral therapy: the Swiss HIV Cohort Study. Clin Infect Dis 33:1931–1937PubMedCrossRef

Boushel R, Gnaiger E, Schjerling P, Skovbro M, Kraunsoe R, Dela F (2007) Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia 50:790–796PubMedPubMedCentralCrossRef

Campuzano V, Montermini L, Molto MD et al (1996) Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271:1423–1427PubMedCrossRef

Casteels K, Ong K, Phillips D, Bendall H, Pembrey M (1999) Mitochondrial 16189 variant, thinness at birth, and type-2 diabetes. ALSPAC study team. Avon Longitudinal Study of Pregnancy and Childhood. Lancet 353:1499–1500PubMedCrossRef

Civitarese AE, Carling S, Heilbronn LK et al (2007) Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med 4:e76PubMedPubMedCentralCrossRef

Cree LM, Patel SK, Pyle A et al (2008) Age-related decline in mitochondrial DNA copy number in isolated human pancreatic islets. Diabetologia 51:1440–1443PubMedCrossRef

Daneman D (2006) Type 1 diabetes. Lancet 367:847–858PubMedCrossRef

De Feyter HM, van den Broek NM, Praet SF, Nicolay K, van Loon LJ, Prompers JJ (2008a) Early or advanced stage type 2 diabetes is not accompanied by in vivo skeletal muscle mitochondrial dysfunction. Eur J Endocrinol 158:643–653PubMedCrossRef

De Feyter HM, Lenaers E, Houten SM et al (2008b) Increased intramyocellular lipid content but normal skeletal muscle mitochondrial oxidative capacity throughout the pathogenesis of type 2 diabetes. FASEB J 22:3947–3955PubMedCrossRef

Dimauro S, Davidzon G (2005) Mitochondrial DNA and disease. Ann Med 37:222–232PubMedCrossRef

Doria A, Patti ME, Kahn CR (2008) The emerging genetic architecture of type 2 diabetes. Cell Metab 8:186–200PubMedPubMedCentralCrossRef

Dunbar DR, Moonie PA, Swingler RJ, Davidson D, Roberts R, Holt IJ (1993) Maternally transmitted partial direct tandem duplication of mitochondrial DNA associated with diabetes mellitus. Hum Mol Genet 2:1619–1624PubMedCrossRef

Fleming JC, Tartaglini E, Steinkamp MP, Schorderet DF, Cohen N, Neufeld EJ (1999) The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter. Nat Genet 22:305–308PubMedCrossRef

Freyer C, Larsson NG (2007) Is energy deficiency good in moderation? Cell 131:448–450PubMedCrossRef

Garcia-Roves P, Huss JM, Han DH et al (2007) Raising plasma fatty acid concentration induces increased biogenesis of mitochondria in skeletal muscle. Proc Natl Acad Sci USA 104:10709–10713PubMedPubMedCentralCrossRef

Guarente L (2008) Mitochondria—a nexus for aging, calorie restriction, and sirtuins? Cell 132:171–176PubMedPubMedCentralCrossRef

Hammer S, Snel M, Lamb HJ et al (2008) Prolonged caloric restriction in obese patients with type 2 diabetes mellitus decreases myocardial triglyceride content and improves myocardial function. J Am Coll Cardiol 52:1006–1012PubMedCrossRef

Hancock CR, Han DH, Chen M et al (2008) High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc Natl Acad Sci USA 105:7815–7820PubMedPubMedCentralCrossRef

Harding AE (1981) Friedreich’s ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain 104:589–620PubMedCrossRef

Herzig S, Long F, Jhala US et al (2001) CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 413:179–183PubMedCrossRef

Hoeks J, Briede JJ, de Vogel J et al (2008) Mitochondrial function, content and ROS production in rat skeletal muscle: effect of high-fat feeding. FEBS Lett 582:510–516PubMedCrossRef

Holloszy JO (1967) Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. J Biol Chem 242:2278–2282PubMed

Holloszy JO (2009) Skeletal muscle “mitochondrial deficiency” does not mediate insulin resistance. Am J Clin Nutr 89:463S–466SPubMedCrossRef

Hoppeler H, Fluck M (2003) Plasticity of skeletal muscle mitochondria: structure and function. Med Sci Sports Exerc 35:95–104PubMedCrossRef

Kelley DE, He J, Menshikova EV, Ritov VB (2002) Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 51:2944–2950PubMedCrossRef

Khan AH, Pessin JE (2002) Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways. Diabetologia 45:1475–1483PubMedCrossRef

Koo SH, Satoh H, Herzig S et al (2004) PGC-1 promotes insulin resistance in liver through PPAR-alpha-dependent induction of TRB-3. Nat Med 10:530–534PubMedCrossRef

Krishnan KJ, Greaves LC, Reeve AK, Turnbull D (2007) The ageing mitochondrial genome. Nucleic Acids Res 35:7399–7405PubMedPubMedCentralCrossRef

Kroemer G (2001) Mitochondrial control of apoptosis. Bull Acad Natl Med 185:1135–1142; discussion 1143PubMed

Krssak M, Falk Petersen K, Dresner A et al (1999) Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 42:113–116PubMedCrossRef

Kuhlmann J, Neumann-Haefelin C, Belz U et al (2003) Intramyocellular lipid and insulin resistance: a longitudinal in vivo 1H-spectroscopic study in Zucker diabetic fatty rats. Diabetes 52:138–144PubMedCrossRef

Labay V, Raz T, Baron D et al (1999) Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness. Nat Genet 22:300–304PubMedCrossRef

Lagouge M, Argmann C, Gerhart-Hines Z et al (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122PubMedCrossRef

Lazar MA (2005) How obesity causes diabetes: not a tall tale. Science 307:373–375PubMedCrossRef

Li X, Monks B, Ge Q, Birnbaum MJ (2007) Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha transcription coactivator. Nature 447:1012–1016PubMedCrossRef

Lin J, Wu PH, Tarr PT et al (2004) Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell 119:121–135PubMedCrossRef

Lin J, Handschin C, Spiegelman BM (2005) Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 1:361–370PubMedCrossRef

Lowell BB, Shulman GI (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307:384–387PubMedCrossRef

Maassen JA, ‘T Hart LM, Van Essen E et al (2004) Mitochondrial diabetes: molecular mechanisms and clinical presentation. Diabetes 53(Suppl 1):103–109CrossRef

Maassen JA, Janssen GM, t Hart LM (2005) Molecular mechanisms of mitochondrial diabetes (MIDD). Ann Med 37:213–221PubMedCrossRef

Maassen JA, Jahangir Tafrechi RS, Janssen GM, Raap AK, Lemkes HH, t Hart LM (2006a) New insights in the molecular pathogenesis of the maternally inherited diabetes and deafness syndrome. Endocrinol Metab Clin North Am 35:385–396, x–xiPubMedCrossRef

Maassen JA, ‘t Hart LM, Janssen GM, Reiling E, Romijn JA, Lemkes HH (2006b) Mitochondrial diabetes and its lessons for common Type 2 diabetes. Biochem Soc Trans 34:819–823PubMedCrossRef

Maassen JA, t Hart LM, Ouwens DM (2007) Lessons that can be learned from patients with diabetogenic mutations in mitochondrial DNA: implications for common type 2 diabetes. Curr Opin Clin Nutr Metab Care 10:693–697PubMedCrossRef

Maechler P, de Andrade PB (2006) Mitochondrial damages and the regulation of insulin secretion. Biochem Soc Trans 34:824–827PubMedCrossRef

Maechler P, Wollheim CB (2001) Mitochondrial function in normal and diabetic beta-cells. Nature 414:807–812PubMedCrossRef

Majander A, Suomalainen A, Vettenranta K et al (1991) Congenital hypoplastic anemia, diabetes, and severe renal tubular dysfunction associated with a mitochondrial DNA deletion. Pediatr Res 30:327–330PubMedCrossRef

Matschinsky F, Liang Y, Kesavan P et al (1993) Glucokinase as pancreatic beta cell glucose sensor and diabetes gene. J Clin Invest 92:2092–2098PubMedPubMedCentralCrossRef

Mensink M, Hesselink MK, Russell AP, Schaart G, Sels JP, Schrauwen P (2007) 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) 31:1302–1310CrossRef

Misu H, Takamura T, Matsuzawa N et al (2007) Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes. Diabetologia 50:268–277PubMedCrossRef

Mogensen M, Sahlin K, Fernstrom M et al (2007) Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes. Diabetes 56:1592–1599PubMedCrossRef

Mootha VK, Lindgren CM, Eriksson KF et al (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34:267–273PubMedCrossRef

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 115:3587–3593PubMedPubMedCentralCrossRef

Morten K, Field P, Ashley N et al (2005) Fetal and neonatal exposure to AZT and low-protein diet affects glucose homeostasis: a model with implications for AIDS prevention. Am J Physiol Endocrinol Metab 289:E1115–1118PubMedCrossRef

Mulder H, Ling C (2009) Mitochondrial dysfunction in pancreatic beta-cells in Type 2 diabetes. Mol Cell Endocrinol 297:34–40PubMedCrossRef

Muoio DM, Newgard CB (2008) Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol 9:193–205PubMedCrossRef

Murphy R, Turnbull DM, Walker M, Hattersley AT (2008) Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation. Diabet Med 25:383–399PubMedCrossRef

Nair KS, Bigelow ML, Asmann YW et al (2008) Asian Indians have enhanced skeletal muscle mitochondrial capacity to produce ATP in association with severe insulin resistance. Diabetes 57:1166–1175PubMedCrossRef

Park KS, Chan JC, Chuang LM et al (2008) A mitochondrial DNA variant at position 16189 is associated with type 2 diabetes mellitus in Asians. Diabetologia 51:602–608PubMedCrossRef

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 100:8466–8471PubMedPubMedCentralCrossRef

Paupe V, Dassa EP, Goncalves S et al (2009) Impaired nuclear Nrf2 translocation undermines the oxidative stress response in Friedreich ataxia. PLoS ONE 4:e4253PubMedPubMedCentralCrossRef

Petersen KF, Shulman GI (2006) Etiology of insulin resistance. Am J Med 119:S10–16PubMedPubMedCentralCrossRef

Petersen KF, Befroy D, Dufour S et al (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300:1140–1142PubMedPubMedCentralCrossRef

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 350:664–671PubMedPubMedCentralCrossRef

Pospisilik JA, Knauf C, Joza N et al (2007) Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes. Cell 131:476–491PubMedCrossRef

Poulton J, Holt IJ (1994) Mitochondrial DNA: does more lead to less? Nat Genet 8:313–315PubMedCrossRef

Poulton J, Deadman ME, Gardiner RM (1989) Duplications of mitochondrial DNA in mitochondrial myopathy. Lancet 1:236–240PubMedCrossRef

Poulton J, O’Rahilly S, Morten KJ, Clark A (1995) Mitochondrial DNA, diabetes and pancreatic pathology in Kearns-Sayre syndrome. Diabetologia 38:868–871PubMedCrossRef

Puigserver P, Rhee J, Donovan J et al (2003) Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 423:550–555PubMedCrossRef

Reardon W, Ross RJ, Sweeney MG et al (1992) Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA. Lancet 340:1376–1379PubMedCrossRef

Richardson DK, Kashyap S, Bajaj M et al (2005) Lipid infusion decreases the expression of nuclear encoded mitochondrial genes and increases the expression of extracellular matrix genes in human skeletal muscle. J Biol Chem 280:10290–10297PubMedCrossRef

Ristow M, Mulder H, Pomplun D et al (2003) Frataxin deficiency in pancreatic islets causes diabetes due to loss of beta cell mass. J Clin Invest 112:527–534PubMedPubMedCentralCrossRef

Ritov VB, Menshikova EV, He J, Ferrell RE, Goodpaster BH, Kelley DE (2005) Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Diabetes 54:8–14PubMedCrossRef

Roden M, Petersen KF, Shulman GI (2001) Nuclear magnetic resonance studies of hepatic glucose metabolism in humans. Recent Prog Horm Res 56:219–237PubMedCrossRef

Rotig A, Bessis JL, Romero N et al (1992) Maternally inherited duplication of the mitochondrial genome in a syndrome of proximal tubulopathy, diabetes mellitus, and cerebellar ataxia. Am J Hum Genet 50:364–370PubMedPubMedCentral

Rotig A, de Lonlay P, Chretien D et al (1997) Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia. Nat Genet 17:215–217PubMedCrossRef

Saltiel AR, Kahn CR (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414:799–806PubMedCrossRef

Schrauwen-Hinderling VB, Roden M, Kooi ME, Hesselink MK, Schrauwen P (2007) Muscular mitochondrial dysfunction and type 2 diabetes mellitus. Curr Opin Clin Nutr Metab Care 10:698–703PubMedCrossRef

Schrauwen-Hinderling VB, Mensink M, Hesselink MK, Sels JP, Kooi ME, Schrauwen P (2008) The insulin-sensitizing effect of rosiglitazone in type 2 diabetes mellitus patients does not require improved in vivo muscle mitochondrial function. J Clin Endocrinol Metab 93:2917–2921PubMedCrossRef

Semple RK, Chatterjee VK, O’Rahilly S (2006) PPAR gamma and human metabolic disease. J Clin Invest 116:581–589PubMedPubMedCentralCrossRef

Silva JP, Kohler M, Graff C et al (2000) Impaired insulin secretion and beta-cell loss in tissue-specific knockout mice with mitochondrial diabetes. Nat Genet 26:336–340PubMedCrossRef

Simmons RA, Suponitsky-Kroyter I, Selak MA (2005) Progressive accumulation of mitochondrial DNA mutations and decline in mitochondrial function lead to beta-cell failure. J Biol Chem 280:28785–28791PubMedCrossRef

Soejima A, Inoue K, Takai D et al (1996) Mitochondrial DNA is required for regulation of glucose-stimulated insulin secretion in a mouse pancreatic beta cell line, MIN6. J Biol Chem 271:26194–26199PubMedCrossRef

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 54:1926–1933PubMedCrossRef

Stump CS, Short KR, Bigelow ML, Schimke JM, Nair KS (2003) Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts. Proc Natl Acad Sci U S A 100:7996–8001PubMedPubMedCentralCrossRef

Stumvoll M, Goldstein BJ, van Haeften TW (2005) Type 2 diabetes: principles of pathogenesis and therapy. Lancet 365:1333–1346PubMedCrossRef

Szendroedi J, Schmid AI, Chmelik M et al (2007) Muscle mitochondrial ATP synthesis and glucose transport/phosphorylation in type 2 diabetes. PLoS Med 4:e154PubMedPubMedCentralCrossRef

‘t Hart LM, Ruige JB, Dekker JM, Stehouwer CD, Maassen JA, Heine RJ (1999) Altered beta-cell characteristics in impaired glucose tolerant carriers of a GAA trinucleotide repeat polymorphism in the frataxin gene. Diabetes 48:924–926CrossRef

‘t Hart LM, Hansen T, Rietveld I et al (2005) Evidence that the mitochondrial leucyl tRNA synthetase (LARS2) gene represents a novel type 2 diabetes susceptibility gene. Diabetes 54:1892–1895PubMedCrossRef

Toledo FG, Menshikova EV, Ritov VB et al (2007) Effects of physical activity and weight loss on skeletal muscle mitochondria and relationship with glucose control in type 2 diabetes. Diabetes 56:2142–2147PubMedCrossRef

Tontonoz P, Spiegelman BM (2008) Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem 77:289–312PubMedCrossRef

Trifunovic A, Larsson NG (2008) Mitochondrial dysfunction as a cause of ageing. J Intern Med 263:167–178PubMedCrossRef

Trifunovic A, Wredenberg A, Falkenberg M et al (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429:417–423PubMedCrossRef

Turner N, Bruce CR, Beale SM et al (2007) Excess lipid availability increases mitochondrial fatty acid oxidative capacity in muscle: evidence against a role for reduced fatty acid oxidation in lipid-induced insulin resistance in rodents. Diabetes 56:2085–2092PubMedCrossRef

Vahsen N, Cande C, Briere JJ et al (2004) AIF deficiency compromises oxidative phosphorylation. Embo J 23:4679–4689PubMedPubMedCentralCrossRef

van den Ouweland JM, Lemkes HH, Ruitenbeek W et al (1992) Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet 1:368–371PubMedCrossRef

Wang H, Antinozzi PA, Hagenfeldt KA, Maechler P, Wollheim CB (2000) Molecular targets of a human HNF1 alpha mutation responsible for pancreatic beta-cell dysfunction. Embo J 19:4257–4264PubMedPubMedCentralCrossRef

Whittaker RG, Schaefer AM, McFarland R, Taylor RW, Walker M, Turnbull DM (2007) Prevalence and progression of diabetes in mitochondrial disease. Diabetologia 50:2085–2089PubMedCrossRef

Williams RS (1986) Mitochondrial gene expression in mammalian striated muscle. Evidence that variation in gene dosage is the major regulatory event. J Biol Chem 261:12390–12394PubMed

Wobser H, Dussmann H, Kogel D et al (2002) Dominant-negative suppression of HNF-1 alpha results in mitochondrial dysfunction, INS-1 cell apoptosis, and increased sensitivity to ceramide-, but not to high glucose-induced cell death. J Biol Chem 277:6413–6421PubMedCrossRef

Wredenberg A, Freyer C, Sandstrom ME et al (2006) Respiratory chain dysfunction in skeletal muscle does not cause insulin resistance. Biochem Biophys Res Commun 350:202–207PubMedCrossRef

Yoon JC, Puigserver P, Chen G et al (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413:131–138PubMedCrossRef

Zhang D, Liu ZX, Choi CS et al (2007) Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance. Proc Natl Acad Sci USA 104:17075–17080PubMedPubMedCentralCrossRef

Titel: Mitochondria and diabetes mellitus: untangling a conflictive relationship?
verfasst von: M. Schiff
S. Loublier
A. Coulibaly
P. Bénit
H. Ogier de Baulny
P. Rustin
Publikationsdatum: 01.12.2009
Verlag: Springer Netherlands
Erschienen in: Journal of Inherited Metabolic Disease / Ausgabe 6/2009
Print ISSN: 0141-8955
Elektronische ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-009-1263-0

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