Current Diabetes Reports

, Volume 5, Issue 2, pp 136–140 | Cite as

Adiponectin: An adipokine linking adipocytes and type 2 diabetes in humans

  • Kazuo Hara
  • Toshimasa Yamauchi
  • Takashi Kadowaki


Adipocyte-derived adiponectin is an insulin-sensitizing and antiatherosclerotic hormone, and replenishment of adiponectin in animal models ameliorated insulin resistance and atherosclerosis. In humans, recent studies have demonstrated that adiponectin level is a good predictor of developing type 2 diabetes and coronary artery disease. Decreasing level of adiponectin is caused by the interaction between genetic factors, such as single nucleotide polymorphisms in the adiponectin gene, and environmental factors, such as high-fat diet. Agents that increase blood level of adiponectin or enhance the actions of adiponectin can be an ideal medicine for ameliorating insulin resistance and type 2 diabetes.


Insulin Resistance Metabolic Syndrome Adiponectin Level Serum Adiponectin Plasma Adiponectin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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References and Recommended Reading

  1. 1.
    Weyer C, Funahashi T, Tanaka S, et al.: Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001, 86:1930–1935.PubMedCrossRefGoogle Scholar
  2. 2.
    Hotta K, Funahashi T, Bodkin NL, et al.: Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 2001, 501:126–133.Google Scholar
  3. 3.
    Arita Y, Kihara S, Ouchi N, et al.: Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999, 257:79–83.PubMedCrossRefGoogle Scholar
  4. 4.
    Yamauchi T, Kamon J, Waki H, et al.: The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001, 7:941–946. Demonstrated for the first time that adiponectin is an insulin-sensitizing hormone and a decrease of adiponectin has a major role in the pathogenesis of insulin resistance and, thus, type 2 diabetes.PubMedCrossRefGoogle Scholar
  5. 5.
    Mori Y, Otabe S, Dina C, et al.: Genome-wide search for type 2 diabetes susceptibility genes in Japanese affected sibpairs. Autosomal scan supplemented with markers for 12 transcription factor genes and adiponectin gene. Diabetes 2002, 51:536–540.PubMedCrossRefGoogle Scholar
  6. 6.
    Kissebah AH, Sonnenberg GE, Myklebust J, et al.: Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci U S A 2000, 97:14478–14483.PubMedCrossRefGoogle Scholar
  7. 7.
    Yamauchi T, Waki H, Kamon J, et al.: Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes. J Clin Invest 2001, 108:1001–1113.PubMedCrossRefGoogle Scholar
  8. 8.
    Kubota N, Terauchi Y, Miki H, et al.: PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell 1999, 4:597–609.PubMedCrossRefGoogle Scholar
  9. 9.
    Hara K, Boutin P, Mori Y, et al.: Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 2002, 51:536–540.PubMedCrossRefGoogle Scholar
  10. 10.
    Kadowaki T, Hara K, Yamauchi T, et al.: Molecular mechanism of insulin resistance and obesity. Exp Biol Med (Maywood) 2003, 228:1111–1117.Google Scholar
  11. 11.
    Comuzzie AG, Funahashi T, Sonnenberg G, et al.: The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab 2001, 86:4321–4325.PubMedCrossRefGoogle Scholar
  12. 12.
    Stumvoll M, Tschritter O, Fritsche A, et al.: Association of the TG polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes 2002, 51:37–41.PubMedCrossRefGoogle Scholar
  13. 13.
    Menzaghi C, Ercolino T, Paola RD, et al.: A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 2002, 51:2306–2312.PubMedCrossRefGoogle Scholar
  14. 14.
    Vasseur F, Helbecque N, Dina C, et al.: Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet 2002, 11:2607–2614.PubMedCrossRefGoogle Scholar
  15. 15.
    Populaire C, Mori Y, Dina C, et al.: Does the -11377 promoter variant of APM1 gene contribute to the genetic risk for type 2 diabetes mellitus in Japanese families? Diabetologia 2003, 46:443–445.PubMedGoogle Scholar
  16. 16.
    Jacob S, Machann J, Rett K, et al.: Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects. Diabetes 1999, 48:1113–1119.PubMedCrossRefGoogle Scholar
  17. 17.
    Krssak M, Falk Petersen K, Dresner A, et al.: Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 1999, 42:113–116.PubMedCrossRefGoogle Scholar
  18. 18.
    Staiger H, Tschritter O, Machann J, et al.: Relationship of serum adiponectin and leptin concentrations with body fat distribution in humans. Obes Res 2003, 11:368–372.PubMedCrossRefGoogle Scholar
  19. 19.
    Spranger J, Kroke A, Mohlig M, et al.: Adiponectin and protection against type 2 diabetes mellitus. Lancet 2003, 361:226–228. Demonstrated for the first time that adiponectin is a predictor of type 2 diabetes developing in humans.PubMedCrossRefGoogle Scholar
  20. 20.
    Lindsay RS, Funahashi T, Hanson RL, et al.: Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 2002, 360:57–58.PubMedCrossRefGoogle Scholar
  21. 21.
    Fumeron F, Aubert R, Siddiq A, et al.: Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study. Diabetes 2004, 53:1150–1157.PubMedCrossRefGoogle Scholar
  22. 22.
    Ouchi N, Kihara S, Arita Y, et al.: Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocytederived macrophages. Circulation 2001, 103:1057–1063.PubMedGoogle Scholar
  23. 23.
    Kazumi T, Kawaguchi A, Sakai K, et al.: Young men with highnormal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure. Diabetes Care 2002, 25:971–976.PubMedCrossRefGoogle Scholar
  24. 24.
    Valsamakis G, Chetty R, McTernan PG, et al.: Fasting serum adiponectin concentration is reduced in Indo-Asian subjects and is related to HDL cholesterol. Diabetes Obes Metab 2003, 5:131–135.PubMedCrossRefGoogle Scholar
  25. 25.
    Yamauchi T, Kamon J, Waki H, et al.: Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem 2003, 278:2461–2468.PubMedCrossRefGoogle Scholar
  26. 26.
    Pischon T, Girman CJ, Hotamisligil GS, et al.: Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004, 291:1730–1737.PubMedCrossRefGoogle Scholar
  27. 27.
    Yang WS, Lee WJ, Funahashi T, et al.: Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 2001, 86:3815–3819.PubMedCrossRefGoogle Scholar
  28. 28.
    Esposito K, Pontillo A, Di Palo C, et al.: Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003, 2:1799–1804.CrossRefGoogle Scholar
  29. 29.
    Faraj M, Havel PJ, Phelis S, et al.: Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab 2003, 88:1594–1602.PubMedCrossRefGoogle Scholar
  30. 30.
    Savage DB, Tan GD, Acerini CL, et al.: Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma. Diabetes 2003, 52:910–917.PubMedCrossRefGoogle Scholar
  31. 31.
    Yu JG, Javorschi S, Hevener AL, et al.: The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 2002, 51:2968–2974.PubMedCrossRefGoogle Scholar
  32. 32.
    Tonelli J, Li W, Kishore P, et al.: Mechanisms of early insulinsensitizing effects of thiazolidinediones in type 2 diabetes. Diabetes 2004, 53:1621–1629.PubMedCrossRefGoogle Scholar
  33. 33.
    Kondo H, Shimomura I, Matsukawa Y, et al.: Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes 2002, 51:2325–2328.PubMedCrossRefGoogle Scholar
  34. 34.
    Waki H, Yamauchi T, Kamon J, et al.: Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003, 278:40352–40363.PubMedCrossRefGoogle Scholar
  35. 35.
    Yamauchi T, Kamon J, Ito Y, et al.: Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003, 423:762–769.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc. 2005

Authors and Affiliations

  • Kazuo Hara
    • 1
  • Toshimasa Yamauchi
    • 1
  • Takashi Kadowaki
    • 1
  1. 1.Department of Metabolic Diseases, Graduate School of MedicineThe University of TokyoTokyoJapan

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