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Neuronal regulation of homeostasis by nutrient sensing

Abstract

In type 2 diabetes and obesity, the homeostatic control of glucose and energy balance is impaired, leading to hyperglycemia and hyperphagia. Recent studies indicate that nutrient-sensing mechanisms in the body activate negative-feedback systems to regulate energy and glucose homeostasis through a neuronal network. Direct metabolic signaling within the intestine activates gut-brain and gut-brain-liver axes to regulate energy and glucose homeostasis, respectively. In parallel, direct metabolism of nutrients within the hypothalamus regulates food intake and blood glucose levels. These findings highlight the importance of the central nervous system in mediating the ability of nutrient sensing to maintain homeostasis. Futhermore, they provide a physiological and neuronal framework by which enhancing or restoring nutrient sensing in the intestine and the brain could normalize energy and glucose homeostasis in diabetes and obesity.

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Figure 1: Proposed mechanisms of nutrient sensing in the gut and the brain.

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Acknowledgements

Work in the Lam laboratory is supported by grants from the Canadian Institute of Health Research (MOP-82701 and 86554) and the Banting and Best Diabetes Centre, as well as the Early Researcher Award from the Ontario Ministry of Research and Innovation (ER08-05-141). T.K.T.L. holds the John Kitson McIvor (1915-1942) Endowed Chair in Diabetes Research and the Canada Research Chair in Obesity at the Toronto General Research Institute and the University of Toronto.

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Correspondence to Tony K T Lam.

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Lam, T. Neuronal regulation of homeostasis by nutrient sensing. Nat Med 16, 392–395 (2010). https://doi.org/10.1038/nm0410-392

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