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Insulin and glucagon signaling in the central nervous system

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Abstract

The prevalence of the obesity and diabetes epidemic has triggered tremendous research investigating the role of the central nervous system (CNS) in the regulation of food intake, body weight gain and glucose homeostasis. This invited review focuses on the role of two pancreatic hormones—insulin and glucagon—that trigger signaling pathways in the brain to regulate energy and glucose homeostasis. Unlike in the periphery, insulin and glucagon signaling in the CNS does not seem to have opposing metabolic effects, as both hormones exert a suppressive effect on food intake and weight gain. They signal through different pathways and alter different neuronal populations suggesting a complementary action of the two hormones in regulating feeding behavior. Similar to its systemic effect, insulin signaling in the brain lowers glucose production. However, the ability of glucagon signaling in the brain to regulate glucose production remains unknown. Future studies that aim to dissect insulin and glucagon signaling in the CNS that regulate energy and glucose homeostasis could unveil novel signaling molecules to lower body weight and glucose levels in obesity and diabetes.

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Acknowledgments

The work discussed in this review produced by the Lam laboratory was supported by a research grant from the Canadian Diabetes Association. M.A.A. is supported by a BBDC scholarship. J.T.Y.Y is supported by a BBDC and University Health Network post-doctoral fellowship. 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.

Conflict of interest

The authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Toronto General Research Institute, University Health Network, Toronto, Canada, M5G 1L7

    Beatrice M. Filippi, Mona A. Abraham, Jessica T. Y. Yue & Tony K. T. Lam

  2. Department of Medicine, University of Toronto, Toronto, Canada, M5S 1A8

    Beatrice M. Filippi, Jessica T. Y. Yue & Tony K. T. Lam

  3. Department of Physiology, University of Toronto, Toronto, Canada, M5S 1A8

    Mona A. Abraham & Tony K. T. Lam

  4. Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada, M5G 2C4

    Tony K. T. Lam

  5. MaRS Centre, 101 College Street, Toronto Medical Discovery Tower, 10th floor, Room 705, Toronto, ON, Canada, M5G 1L7

    Tony K. T. Lam

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  1. Beatrice M. Filippi
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  2. Mona A. Abraham
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  3. Jessica T. Y. Yue
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  4. Tony K. T. Lam
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Correspondence to Tony K. T. Lam.

Additional information

Beatrice M. Filippi and Mona A. Abraham contributed equally to this work

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Filippi, B.M., Abraham, M.A., Yue, J.T.Y. et al. Insulin and glucagon signaling in the central nervous system. Rev Endocr Metab Disord 14, 365–375 (2013). https://doi.org/10.1007/s11154-013-9258-4

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