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Dr. MICHEL RISTOW

Dr. MICHEL RISTOW

           Michael Ristow (b April 24, 1967) is a Germanmedical researcher who has published influential articles on the metabolic basis of human diseases, including type 2 diabetes, obesity and cancer, as well as general aging processes. Amongst more than 50 peer-reviewed scientific publications, Ristow published a seminal article describing a genetic mutation associated with extreme human obesity. [1]

Ristow was born in Lübeck in the North of Germany. He graduated at the University of Bochum in 1992 and received his M.D. from University of Bochum in 1996. He was appointed to the University of Jena in 2005 as a full professor in nutritional science.

Ristow’s laboratory has provided direct evidence supporting the so-called Warburg hypothesis. Specifically Ristow has shown that forced metabolic activity and respiration of mitochondria efficiently blocks cancer growth [2] as anticipated by Otto Heinrich Warburg as early as in 1924.

In 2007, Ristow’s group published evidence which could explain the basis of the observed extension of lifespan by restriction of sugar intake. In experiments on a model organism, the worm Caenorhabditis elegans, they found that lowering the availability of glucose extended the lifespan of the worms. It has been known since the 1930s that restricting calories while maintaining adequate amounts of other nutrients extends lifespan across a broad range of organisms. The mechanism has been proposed as a change in the activity of the sirtuins. Interestingly, Michael Ristow shows in his article that this effect can also occur independent of sirtuins, since worms deficient for sirtuins still show extended life span in states of sugar restriction.[3]

Most importantly, Ristow's research further suggests that this is a mitohormetic effect. Hormesis is a controversial concept in which it has been demonstrated that the induction of a stress can lengthen lifespan in some species. Ristow's interpretation was that in response to a decrease in glycolytic energy production, the worms have to generate ATP by oxidative phosphorylation in the mitochondria, leading to increased production of reactive oxygen species. In response, the organism produces more defenses against oxidative stress, including increased production of catalase. Supplementation with antioxidants abolishes the increase in lifespan, and so does disruption of an AMP-kinase but not disruption of sirtuins.[3]

These findings bring into question Denham Harman's free radical theory of aging, and provide a mechanistic basis to question the application of antioxidants to human health. [4]

References

  1. ^ Michael Ristow, M.D., Dirk Müller-Wieland, M.D., Andreas Pfeiffer, M.D., Wilhelm Krone, M.D., and C. Ronald Kahn, M.D. (October 1, 1998). "Obesity Associated with a Mutation in a Genetic Regulator of Adipocyte Differentiation". The New England Journal of Medicine 339 (14): 953–959. doi:10.1056/NEJM199810013391403. PMID 9753710. http://content.nejm.org/cgi/content/abstract/339/14/953/. 
  2. ^ Tim J. Schulz, Rene Thierbach, Anja Voigt, Gunnar Drewes, Brun Mietzner, Pablo Steinberg, Andreas F. H. Pfeiffer and Michael Ristow (2006). "Induction of Oxidative Metabolism by Mitochondrial Frataxin Inhibits Cancer Growth: Otto Warburg Revisited". J. Biol. Chem. 281 (2): 977–981. doi:10.1074/jbc.M511064200. PMID 16263703. http://www.jbc.org/cgi/reprint/281/2/977.pdf. 
  3. ^ a b Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M (2007). "Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress". Cell Metab. 6 (4): 280–93. doi:10.1016/j.cmet.2007.08.011. PMID 17908557. 
  4. ^ Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2007). "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis". JAMA 297 (8): 842–57. doi:10.1001/jama.297.8.842. PMID 17327526.
Publications Ristow Lab

Ranking 'Ernährungsforschung' (2007) / 'Hormon-/Stoffwechselforschung' (2006)

2010

Birringer M, Lington D, Vertuani S, Manfredini S, Scharlau D, Glei M and Ristow M: Proapoptotic effects of long chain vitamin E metabolites in HepG2 cells are mediated by oxidative stress. Free Radical Biology and Medicine, in press (2010)

Ristow M, Zarse K: How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis). Exp Gerontol, 45, 410-8 (2010).

Fezeu L, Henegar A, Kesse-Guyot E, Julia C, Galan P, Hercberg S, Ristow M, Czernichow S: Physical Activity does not Influence the Effect of Antioxidant Supplementation at Nutritional Doses on the Incidence of Impaired Fasting Glucose: A 7.5 Year Post-hoc Analysis from the SU.VI.MAX Study. Horm Metab Res, in press (2010)

Kuhlow D, Zarse K, Voigt A, Schulz TJ, Petzke KJ, Schomburg L, Pfeiffer AF, Ristow M: Opposing effects of dietary sugar and saturated fat on cardiovascular risk factors and glucose metabolism in mitochondrially impaired mice, Eur. J. Nutr., in press (2010)

Birringer M: Analysis of vitamin E metabolites in biological specimen. Mol. Nutr. Food Res. 54, 588-598, (2010).

Wuensch T, Thilo F, Krueger K, Scholze A, Ristow M, Tepel M: High glucose-induced oxidative stress increases transient receptor potential (TRP) channel expression in human monocytes. Diabetes, in press (2010).

Blüher M, Stumvoll M, Kahn CR, Ristow M: High baseline vitamin C levels do not prevent a positive outcome of  a lifestyle intervention (comment letter). Diabetes Care, 33:c17 (2010).

2009

Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Blüher M: Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci USA, 106:8865-70 (2009) --- corresponding entries:
--- New York Times--- BBC--- Forbes--- Reuters--- Scientific American--- Spiegel--- Ärzteblatt--- Stern--- Focus--- Süddeutsche--- Handelsblatt--- FTD--- Welt--- Tagesspiegel--- Bild--- Heute--- N24--- n-TV

Ripcke J, Zarse K, Ristow M, Birringer M: Small-molecule targeting to the mitochondrial compartment by an endogenously cleaved reversible tag. ChemBioChem, 10:1689-96 (2009)

Fex M, Haemmerle G, Wierup N, Dekker-Nitert M, Rehn M, Ristow M, Zechner R, Sundler F, Holm C, Eliasson L, Mulder H: A beta cell-specific knockout of hormone-sensitive lipase in mice results in hyperglycaemia and disruption of exocytosis. Diabetologia, 52:271–280 (2009)

Perwitz N, Wenzel J, Wagner I, Büning J, Drenckhan M, Zarse K, Ristow M, Lilienthal W, Lehnert H, Klein J: Cannabinoid type 1 receptor blockade induces transdifferentiation towards a brown fat phenotype in white adipocytes, Diab Obes Metab 12:158-166 (2009)

2008

Zarse K, Ristow M: Antidepressants of the serotonin-antagonist type increase body fat and decrease lifespan of adult Caenorhabditis elegans. PLoS One, 3: e4062 (2008)

Schwiertz A, Deubel S, Birringer M: Bioactivation of selenocysteine derivatives by beta-lyases present in common gastrointestinal bacterial species. Int J Vitam Nutr Res, 78:169-74(2008)

Isken F, Pfeiffer AFH, Nogueiras R, Osterhoff MA, Ristow M, Thorens B, Tschöp MH, Weickert MO: Deficiency of Glucose-Dependent Insulinotropic Polypeptide (GIP) Receptor Prevents Ovariectomy-Induced Obesity in Mice. Am J Physiol Endocrinol Metab, 295: E350-5 (2008)

Ristow M: Glukosestoffwechsel und Tumorwachstum [Glucose metabolism and cancer growth]. Der Onkologe, 14: 22-30 (2008)

Zimmermann S, Zarse K, Schulz TJ, Siems K, Müller-Kuhrt L, Birringer M, Ristow M: A cell-based high-throughput assay system reveals modulation of oxidative and non-oxidative glucose metabolism due to commonly used organic solvents. Horm Metab Res, 40: 29-37 (2008)

2007

Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M: Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress, Cell Metab, 6: 280-293 (2007).   --- corresponding Reuters entry --- corresponding ScienceSignaling entry  --- corresponding Eurekalert entry   --- corresponding Faculty 1000 entry --- 

Birringer M, Kuhlow D, Pfluger PT, Landes N, Schulz TJ, Glaubitz M, Florian S, Pfeiffer AF, Schuelke M, Brigelius-Flohé R, Ristow M: Improved glucose metabolism in mice lacking α-tocopherol transfer protein, Eur J Nutr, 46: 397-405 (2007).

Pomplun D, Voigt A, Schulz TJ, Thierbach R, Pfeiffer, AF, Ristow M: Reduced expression of mitochondrial frataxin in mice exacerbates diet-induced obesity. Proc Natl Acad Sci USA, 104: 6377-6381 (2007).  --- corresponding 'Spiegel Online' article

Fex M, Wierup N, Dekker Nitert M, Ristow M, Mulder H: RIP2-Cre mice bred onto a pure C57BL/6J background exhibit unaltered glucose tolerance. J Endocrinology, 194: 551-5 (2007)

Adler G, Bischoff S, Daniel H, Grüters A, Haller D, Haller H, Häring HU, Illig T, Joost HG, Köhrle J, Kramer W, Lehnert H, Pfeiffer A, Ristow M, Roscher A, Ruth P, Schick F, Ziegler AG: Kapitel 4.2. Ernährung und Stoffwechselerkrankungen sowie endokrinologische Erkrankungen; In: Adler G, Balling R, Einhäupl K, Seeger W: Roadmap für das Gesundheitsforschungsprogramm der Bundesregierung, Eigenverlag des Gesundheitsforschungsrats, Bonn/Berlin 2007   --- corresponding English summary

Schulz TJ, Glaubitz M, Kuhlow D, Thierbach R, Birringer M, Steinberg P, Pfeiffer AFH, Ristow M: Variable expression of Cre recombinase transgenes precludes reliable prediction of tissue-specific gene disruption by tail-biopsy genotyping, PLoS ONE 2 (10): e1013 (2007).

Pomplun D, Florian S, Schulz TJ, Pfeiffer AFH, Ristow M: Alterations of pancreatic beta-cell mass and islet number due to Ins2-controlled expression of cre recombinase: RIP-cre revisited part 2. Horm Metab Res, 39: 336-40 (2007).

Ristow M, Birringer M, Schulz TJ: Prävention von Krankheiten und Steigerung der Lebenserwartung durch Kalorienrestriktion [Calorie Restriction Mediates Increased Disease Resistance and Life Expectancy]. Aktuelle Ernähr Med, 32: 104-109 (2007).

Neuzil J, Tomasetti M, Zhao Y, Dong LF, Birringer M, Wang XF, Low P, Wu K, Salvatore BA, Ralph SJ.: Vitamin E analogs, a novel group of 'mitocans,' as anti-cancer agents: The importance of being redox-silent. Mol Pharmacology, 77: 1185-1199 (2007).

Wang X-F, Birringer M, Dong L-F, Veprek P, Low P, Swettenham E, Stanic M, Yuan L-H, Zobalova R, Wu K, Ralph S-J, Ledvina M, and Neuzil J : A peptide conjugate of vitamin E succinate targets breast cancer cells with high erbB2 expression . Cancer Res, 67: 3337-3344 (2007).

Zarse K, Schulz TJ, Birringer M, Ristow M: Impaired respiration is positively correlated with decreased life span in Caenorhabditis elegans models of Friedreich Ataxia. FASEB Journal, 21: 1271-1275 (2007).

Bobbert T, Wegewitz U, Brechtel L, Freudenberg M, Mai K, Möhlig M, Diederich S, Ristow M, Rochlitz H, Pfeiffer AFH, Spranger J: Adiponectin oligomers in human serum during acute and chronic exercise: relation to lipid metabolism and insulin sensitivity. Int J Sports Med, 28: 1-8 (2007).

2006

Schulz TJ, Thierbach R, Voigt A, Drewes G, Mietzner B, Steinberg P, Pfeiffer AFH, Ristow M: Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth: Otto Warburg revisited. J Biol Chem, 281: 977-81 (2006).

Lee JY, Ristow M, Lin X, White MF, Magnuson MA, Hennighausen L: RIP-Cre revisited - Evidence for impairments of pancreatic beta-cell function. J Biol Chem, 281: 2649-53 (2006).

Ristow M: Oxidative metabolism in cancer growth. Curr Opin Clin Nutr Metabol, 9: 339-345 (2006).

Meyer C, Carlqvist H, Vorgerd M, Schöls L, Östenson C-G, Ristow M: Regular insulin secretory oscillations despite impaired ATP synthesis in Friedreich Ataxia patients. Horm Metabol Res, 38: 683-7 (2006).

Möhlig M, Freundeberg M, Bobbert T, Ristow M, Rochlitz H, Weickert MO, Pfeiffer AFH, Spranger J: Acetylsalicylic acid improves lipid-induced insulin resistance in healthy men. J Clin Endocrin Metab, 91: 964-7 (2006).

Isken F, Schulz TJ, Möhlig, Pfeiffer AFH, Ristow M: Chemical inhibition of citrate metabolism alters glucose metabolism in mice. Horm Metabol Res, 38: 543–545 (2006).

Isken F, Schulz TJ, Weickert MO, Pfeiffer AFH, Ristow M: Chemical inhibition of citrate metabolism alters body fat content in mice. Horm Metab Res, 38: 134-6 (2006).

Möhlig M, Spranger J, Ristow M, Pfeiffer AF, Schill T, Schlosser HW, Moltz L, Brabant G, Schofl C: Predictors of abnormal glucose metabolism in women with polycystic ovary syndrome: Eur J Endocrinol, 154: 295-301 (2006).

Andresen H, Grötzinger C, Zarse K, Kreuzer OJ, Ehrentreich-Förster E, and Bier FF: Functional peptide microarrays for specific and sensitive antibody diagnostics. Proteomics, 113: 655-633 (2006).

Andresen H, Grötzinger C, Zarse K, Birringer M, Kreuzer OJ, Ehrentreich-Förster E, Bier FF: Peptide microarrays with site-specific immobilized synthetic peptides for antibody diagnostics. Sensors & Actuators B, 113: 655-633 (2006).

Andresen H, Zarse K, Grötzinger C,Hollidt JM,Ehrentreich-Förster E,Bier FF, Kreuzer OJ: Development of peptide microarrays for epitope mapping of antibodies against the human TSH receptor. J Immunolog Meth, 11-18 (2006).

2005

Jürgens H, Haass W, Castaneda TR, Schürmann A, Koebnick C, Dombrowski F, Otto B, Nawrocki-AR, Scherer PE, Spranger J, Ristow M, Joost HG, Havel PJ, Tschöp M: Consuming fructose-sweetened beverages increases body adiposity in mice. Obes Res, 13:1150-6 (2005).

Thierbach R, Schulz TJ, Isken F, Voigt A, Mietzner B, Drewes G, von Kleist-Retzow JC, Wiesner RJ, Magnuson MA, Puccio H, Pfeiffer AFH, Steinberg P, Ristow M: Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span, and tumor growth in mice. Hum Mol Genet, 14: 3857-64 (2005).

Schoenfeld RA, Napoli E, Wong A, Zhan S, Morin D, Buckpitt AR, Taroni F, Lonnerdal B, Ristow M, Puccio H, Cortopassi GA: Frataxin deficiency alters heme pathway transcripts and decreases mitochondrial heme metabolites in mammalian cells. Hum Mol Genet, 14: 3787-99 (2005).

Boggiano MM, Chandler PC, Oswald KD, Rodgers RJ, Blundell JE, Ishii Y, Beattie AH, Holch P, Allison DB, Schindler M, Arndt K, Rudolf K, Mark M, Schoelch C, Joost HG, Klaus S, Thöne-Reineke C, Benoit SC, Seeley RJ, Beck-Sickinger AG, Koglin N, Raun K, Madsen K, Wulff BS, Stidsen CE, Birringer M, Kreuzer OJ, Deng XY, Whitcomb DC, Halem H, Taylor J, Dong J, Datta R, Culler M, Ortmann S, Castañeda TR, Tschöp M: PYY3-36 as an anti-obesity drug target. Obesity Rev, 6: 307-22 (2005).

Weickert MO, Mohlig M, Koebnick C, Holst JJ, Namsolleck P, Ristow M, Osterhoff M, Rochlitz H, Rudovich N, Spranger J, Pfeiffer AFH: Impact of cereal fibre on glucose-regulating factors, Diabetologia, 48: 2343-2353 (2005).

Shellie RA, Welthagen W, Zrostlikova J, Spranger J, Ristow M, Fiehn O, Zimmermann R: Statistical methods for comparing comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry results: metabolomic analysis of mouse tissue extracts. J Chromatogr A 1086: 83-90 (2005).

Welthagen W, Shellie R, Ristow M, Spranger J, Zimmermann R, Fiehn O Comprehensive two dimensional gas chromatography – time of flight mass spectrometry, GCxGC-TOF for high resolution metabolomics: Biomarker discovery on spleen tissue extracts of obese NZO compared to lean C57BL/6 mice. Metabolomics, 1: 57-65 (2005).

Rudovich NN, Dick D, Möhlig M, Otto B, Spranger J, Rochlitz HJ, Ristow M, Tschoep M, Pfeiffer AFH: Ghrelin is not suppressed in hyperglycemic clamps by gastric inhibitory polypeptide and arginine. Regul Pept, 127: 95-99 (2005).

Kluth D, Landes N, Pfluger P, Muller-Schmehl K, Weiss K, Bumke-Vogt C, Ristow M, Brigelius-Flohe R: Modulation of Cyp3a11 mRNA expression by alpha-tocopherol but not gamma-tocotrienol in mice. Free Rad Biol Med, 38: 507-14 (2005).

2004

Ristow M: Neurodegenerative disorders associated with diabetes mellitus. J Mol Med, 82: 510-529 (2004).

Möhlig M, Isken F, Ristow M: Impaired mitochondrial activity and insulin-resistant offspring of patients with type 2 diabetes (comment letter). New Engl J Med, 350: 2420-21 (2004).

Ristow M: Aspekte der mitochondrialen Pathogenese des Diabetes mellitus. Diab Stoffw, 13: 177-179 (2004).

Pomplun D, Möhlig M, Spranger J, Pfeiffer AFH, Ristow M: Elevation of blood glucose following anaesthetic treatment in C57Bl/6 mice. Horm Metab Res, 36: 67-69 (2004).

Möhlig M, Spranger J, Osterhoff M, Ristow M, Pfeiffer AF, Schill T, Schlosser HW, Brabant G, Schöfl C: The polycystic ovary syndrome per se is not associated with increased chronic inflammation. Eur J Endocrinol, 150: 525-32 (2004).

Tschöp M, Castaneda TR, Joost HG, Thöne-Reineke C, Ortmann S, Klaus S, Hagan MM, Chandler PC, Oswald KD, Benoit SC, Seeley RJ, Kinzig KP, Moran TH, Beck-Sickinger AG, Koglin N, Rodgers RJ, Blundell JE, IshiiI Y, Beattie AH, Holch P, Allison DB, Raun K, Madsen K, Wulff BS, Stidsen CE, Birringer M, Kreuzer OJ, Schindler M, Arndt K, Rudolf K, Mark M, Deng XY, Withcomb DC, Halem H, Taylor J, Dong J,. Datta R, Culler M, Craney S, Flora D, Skiley D, Heiman ML: Does gut hormone PYY3–36 decrease food intake in rodents? Nature 430: 166 (2004).

Möhlig M, Boeing H, Spranger J, OSterhoff M, Kroke A, Fisher A, Bergmann MM, Ristow M, Hoffmann K, Pfeiffer AFH: Body mass index and C-174G interleukin-6 promoter polymorphism interact in predicting type 2 diabetes. J Clin Endocrinol Metab, 89: 1885-90 (2004)

Spranger J, Mohlig M, Wegewitz U, Ristow M, Pfeiffer AF, Schill T, Schlosser HW, Brabant G, Schöfl C: Adiponectin is independently associated with insulin sensitivity in women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 61: 738-46 (2004).

Winkler D,Morbach G,Hessenius C, Ritzke M, Schmidt J, Birringer M, Kreuzer OJ: High-throughput solid phase parallel synthesis of peptides in 96-well format. Pharma Chem 7-8: 34-36 (2004).

Neuzil J, Tomasetti M, Mellick AS, Alleva R, Salvatore BA, Birringer M, Fariss MW: Vitamin E analogues: a new class of inducers of apoptosis with selective anti-cancer effects. Curr Cancer Drug Targets. 4: 355-72, (2004)

Spranger J, Mohlig M, Wegewitz U, Ristow M, Pfeiffer AF, Schill T, Schlosser HW, Brabant G, Schöfl C: Adiponectin is independently associated with insulin sensitivity in women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 61: 738-46 (2004).

2003

Ristow M, Mulder H, Pomplun D, Schulz TJ, Müller-Schmehl K, Krause A, Fex M, Puccio H, Müller J, IskenF, Spranger J, Müller-Wieland D, Magnuson MA, Möhlig M, Koenig M, Pfeiffer AFH: Frataxin-deficiency in pancreatic islets causes diabetes due to loss of beta-cell mass, J Clin Invest, 112: 527-534 (2003).

Norris AW, Chen L, Fisher SJ, Szanto I, Ristow M, Joszi AC, Hirshman MF, Goodyear LJ, Spiegelman BM, Gonzalez FJ, Kahn CR: Muscle-specific PPARgamma deficient mice develop increased adiposity and insulin resistance but respond to thiazolidinediones, J Clin Invest, 112: 608-618 (2003).

Kreuzer OJ, Birringer M, Zarse K, Henkel J, Bier FF, Thurk M, Zinsser W: Novel tools and applications in parallel peptide synthesis. Biopolymers 71: 353, (2003)

Landes N, Birringer M, Brigelius-Flohé R: Homologous metabolic and gene activating routes for vitamin E and K. Mol Aspects Med, 24: 337-44, (2003)

Birringer M, EyTina JH, Salvatore BA, Neuzil J: Vitamin E analogues as inducers of apoptosis: structure-function relation: Br J Canc 88: 1948-1955, (2003)

Landes N, Pfluger P, Kluth D, Birringer M, Rühl R, Böl G, Glatt H, Brigelius-Flohé R: Vitamin E activates gene expression via the pregnane X receptor. Biochem Pharmacol. 65: 269-273, (2003)

Spranger J, Ristow M, Otto B, Heldwein W, Tschöp M, Pfeiffer AFH, Möhlig M. Postprandial decrease of human plasma ghrelin in the absence of insulin. J Endocrinol Invest 26: RC19-22 (2003)

Tschöp M, Arlt W, Anker SD, Ristow M: Medizinische Forschungsbedingungen in Deutschland: Eine Aufforderung auszuwandern. Dtsch Arztebl 100:A 1916-1919 (2003).

Tschöp M, Arlt W, Anker SD, Ristow M: Perspektiven des medizinisch-akademischen Nachwuchses in Deutschland. Der Internist 44: M114 - M118 (2003).

Tschöp M, Arlt W, Anker SD, Ristow M: Perspektiven des medizinisch-akademischen Nachwuchses in Deutschland. Der Chirurg 10: M304 - M307 (2003) (Nachdruck).

Tschöp M, Arlt W, Anker SD, Ristow M: Perspektiven des medizinisch-akademischen Nachwuchses in Deutschland. Der Urologe 42: 1290-3 (2003) (Nachdruck).

Spranger J, Kroke A, Möhlig M, Hoffmann K, Bergmann MM, Ristow M, Boeing H, Pfeiffer AFH: Inflammatory cytokines and the risk to develop type 2 diabetes mellitus: Results of the prospective population based EPIC-Potsdam study. Diabetes, 52: 812-817 (2003)

Spranger J, Kroke A, Möhlig M, Bergmann MM, Ristow M, Boeing H, Pfeiffer AFH: Adiponectin and protection against diabetes mellitus. Lancet, 361: 226-228 (2003)

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