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Failure of adipocyte differentiation causes type II diabetes mellitus?

Nature Genetics volume 26, page 13 (2000)Cite this article

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Anand and Chada1 have reported that knockouts of Hmgic prevent adipocyte differentiation and therefore might serve as a target for obesity. Prevention of adipocyte differentiation, however, is destined to exchange obesity for diabetes and suggests an interesting hypothesis: that type II diabetes is the result of the inability of the adipose organ to expand to accommodate excess calories and that type II diabetes in the centrally obese, in spite of their unlikely phenotype, is a form of lipodystrophy. If the adipose organ is unable to accommodate excess energy, the calories are stored in the liver, muscles and, with the development of diabetes, in the blood and urine. This is most clearly seen in acquired total lipodystrophy where a positive energy balance begets diabetes2, and is revealed in obese type II diabetics when, early in their disease, caloric restriction reverses the diabetes.

This is supported by Gavrilova et al.3, who reversed the diabetes in a mouse model of lipodystrophy by surgically implanting adipose tissue. It is supported by Okuno et al.4, who found that thiazolidinediones improved insulin sensitivity in Zucker rats by increasing the number of new adipocytes. It is supported in studies in obese Pima Indians, in which the best correlation with the onset of diabetes is with adipocyte size, suggesting difficulty in differentiating new ones5. It is supported by the observation that insulin sensitivity during overfeeding correlates with the recruitment of new adipocytes6, and that the in vitro yield of newly differentiated adipocytes is greater in lean than in obese subjects.

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References

  1. Anand, A. & Chada, K. Nature Genet. 24, 377–380 (2000).

    Article  CAS  Google Scholar 

  2. Robbins, D.C. et al. Metabolism 28, 908–916 (1979).

    Article  CAS  Google Scholar 

  3. Gavrilova, O. et al. J. Clin. Invest. 105, 271–278 (2000).

    Article  CAS  Google Scholar 

  4. Okuno, A. et al. J. Clin. Invest. 101, 1354–1361 (1998).

    Article  CAS  Google Scholar 

  5. Paolisso, G. et al. Diabetologia 38, 1213–1217 (1995).

    Article  CAS  Google Scholar 

  6. Kashiwagi, A. et al. Metabolism 34, 364–370 (1985).

    Article  CAS  Google Scholar 

  7. Randle, P.J., Kales, C.N., Garland, P.B. & Newshome, E.A. Lancet 1, 785–789 (1963).

    Article  CAS  Google Scholar 

  8. McGarry, J.D. & Dobbins, R.L. Diabetologia 42, 128–138 (1999).

    Article  CAS  Google Scholar 

  9. Unger, R.H., Shou, Y. & Orci, L. Proc. Natl Acad. Sci. USA 96, 2327–2332 (1999).

    Article  CAS  Google Scholar 

  10. Knittle, J.L. & Hirsch, J. J. Clin. Invest. 47, 2091–2097 (1968).

    Article  CAS  Google Scholar 

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  1. University of Vermont, Underhill, Vermont, USA

    Elliot Danforth Jr

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Danforth, E. Failure of adipocyte differentiation causes type II diabetes mellitus?. Nat Genet 26, 13 (2000). https://doi.org/10.1038/79111

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