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Rethinking the central causes of diabetes

Nature Medicine volume 9, pages 645–647 (2003)Cite this article

Is diabetes a disease of the central nervous system? New data point in that direction. Alterations of the levels of long chain fatty acids in the hypothalamus are now shown to influence glucose homeostasis (pages 756–761).

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Figure 1: Neurons in the hypothalamus (in particular, the arcuate nucleus) are primary targets of a number of key hormones and metabolic cues.

Kimberly Homer

References

  1. Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 (1994).

    Article  CAS  Google Scholar 

  2. Obici, S., Feng, Z., Arduni, A., Conti, R. & Rossetti, L. Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat. Med. 9, 756–761 (2003).

    Article  CAS  Google Scholar 

  3. Schwartz, M.W. Progress in the search for neuronal mechanisms coupling type 2 diabetes to obesity. J. Clin. Invest. 108, 963–964 (2001).

    Article  CAS  Google Scholar 

  4. Loftus, T.M. et al. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 288, 2379–2381 (2000).

    Article  CAS  Google Scholar 

  5. Obici, S. et al. Central administration of oleic acid inhibits glucose production and food intake. Diabetes 51, 271–275 (2002).

    Article  CAS  Google Scholar 

  6. Wortman, R.D., Clegg, D.J., D'Alessio, D., Woods, S.C. & Seeley, R.J. C75 inhibits food intake by increasing CNS glucose metabolism. Nat Med 9, 483–485 (2003).

    Article  CAS  Google Scholar 

  7. Briscoe, C.P. et al. The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J. Biol. Chem. 278, 11303–11311 (2003).

    Article  CAS  Google Scholar 

  8. Itoh, Y. et al. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 422, 173–176 (2003).

    Article  CAS  Google Scholar 

  9. Cowley, M.A. et al. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37, 649–661 (2003).

    Article  CAS  Google Scholar 

  10. Cowley, M.A. et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411, 480–484 (2001).

    Article  CAS  Google Scholar 

  11. Marks, D.L. & Cone, R.D. Central melanocortins and the regulation of weight during acute and chronic disease. Recent Prog. Horm. Res. 56, 359–375 (2001).

    Article  CAS  Google Scholar 

  12. Farooqi, I.S. et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N. Engl. J. Med. 348, 1085–1095 (2003).

    Article  CAS  Google Scholar 

  13. Obici, S. et al. Central melanocortin receptors regulate insulin action. J. Clin. Invest. 108, 1079–1085 (2001).

    Article  CAS  Google Scholar 

  14. Fan, W. et al. The central melanocortin system can directly regulate serum insulin levels. Endocrinology 141, 3072–3079 (2000).

    Article  CAS  Google Scholar 

  15. Kishi, T. et al. Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. J. Comp. Neurol. 457, 213–235 (2003).

    Article  CAS  Google Scholar 

  16. Makimura, H. et al. Cerulenin mimics effects of leptin on metabolic rate, food intake, and body weight independent of the melanocortin system, but unlike leptin, cerulenin fails to block neuroendocrine effects of fasting. Diabetes 50, 733–739 (2001).

    Article  CAS  Google Scholar 

  17. Shimomura, I., Hammer, R.E., Ikemoto, S., Brown, M.S. & Goldstein, J.L. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 401, 73–76 (1999).

    Article  CAS  Google Scholar 

  18. Oral, E.A. et al. Leptin-replacement therapy for lipodystrophy. N. Engl. J. Med. 346, 570–578 (2002).

    Article  CAS  Google Scholar 

  19. Bernard, C. Leçons de Physiologie Experimentale Appliquée à la Médecine. (Baillière et Fils, Paris, 1855).

  20. Stevenson, J.A.F. Neural control of food and water intake. in The Hypothalamus (eds. Haymaker, W., Anderson, E. & Nauta, W.J.H.) 524–621 (Charles C. Thomas, Springfield, Illinois, 1969).

    Google Scholar 

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Authors and Affiliations

  1. Departments of Medicine and Neurology, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Program in Neuroscience, Harvard Medical School, Boston, 02215, Massachusetts, USA

    Joel K Elmquist & Jacob N Marcus

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  1. Joel K Elmquist
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  2. Jacob N Marcus
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Correspondence to Joel K Elmquist.

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Elmquist, J., Marcus, J. Rethinking the central causes of diabetes. Nat Med 9, 645–647 (2003). https://doi.org/10.1038/nm0603-645

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