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The Beta Cell in Metabolic Syndrome

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A Systems Biology Approach to Study Metabolic Syndrome

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Abstract

The pancreatic beta cell is equipped with a highly sophisticated machinery to precisely sense the metabolic status of the organism and secrete the exactly appropriate amount of insulin to maintain blood glucose levels in a very narrow range. When the Metabolic Syndrome develops, insulin resistance imposes an additional burden on the beta cell, which then hypersecretes insulin to meet the demand. In the majority of individuals, the beta cell can sustain this additional workload and maintain normoglycemia. In a subset of predisposed individuals however, this compensatory response eventually fails and diabetes develops. Once diabetes is established, beta-cell function continues to deteriorate over time. The molecular and cellular mechanisms underlying beta-cell failure are not fully understood, although several hypotheses have been proposed. Amongst these, glucolipotoxicity; defective mitochondrial metabolism and oxidative stress; inflammation; amyloid deposits, disruption of autophagic flux; endoplasmic reticulum stress; beta-cell dedifferentiation and exhaustion from chronic hypersecretion probably contribute to some extent, perhaps at various stages of the disease progression and differently between individuals. Thus, beta-cell failure is likely mediated by a number of interrelated and complex mechanisms, which is reflected in the inability of the current therapeutic options to significantly slow down disease progression. This provides a strong argument for early interventions aimed at preventing the functional demise of pancreatic beta cells in the Metabolic Syndrome.

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Acknowledgements

Work performed in our laboratory was supported by the US National Institutes of Health (R01-DK58096 from NIDDK). B.Z. was supported by the Montreal Diabetes Research Center/ Merck Frosst post-doctoral fellowship and Eli Lilly Canada. G.F. was supported by a post-doctoral fellowship from the Canadian Diabetes Association. J.A. and M.S. were supported by doctoral fellowships from the Fonds de Recherche Québec—Santé. V.P. holds the Canada Research Chair in Diabetes and Pancreatic Beta-cell Function.

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  1. Montreal Diabetes Research Center, CRCHUM—Technopôle Angus, Rachel Est, H1W 4A4, 2901, Montréal, QC, Canada

    Bader Zarrouki, Ghislaine Fontés, Meriem Semache, Julie Amyot & Vincent Poitout DVM, PhD

  2. Department of Medicine, University of Montreal, Montreal, QC, Canada

    Bader Zarrouki, Ghislaine Fontés & Vincent Poitout DVM, PhD

  3. Department of Biochemistry, University of Montreal, Montreal, QC, Canada

    Meriem Semache, Julie Amyot & Vincent Poitout DVM, PhD

  4. Department of Nutrition, University of Montreal, Montreal, QC, Canada

    Vincent Poitout DVM, PhD

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  1. Bader Zarrouki
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Correspondence to Vincent Poitout DVM, PhD .

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  1. VTT Technical Research Centre of Finland, Espoo, Finland

    Matej Orešič

  2. Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom

    Antonio Vidal-Puig

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Zarrouki, B., Fontés, G., Semache, M., Amyot, J., Poitout, V. (2014). The Beta Cell in Metabolic Syndrome. In: Orešič, M., Vidal-Puig, A. (eds) A Systems Biology Approach to Study Metabolic Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-319-01008-3_5

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