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The emerging role of TRIB3 as a gene affecting human insulin resistance and related clinical outcomes

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Abstract

Type 2 diabetes is becoming epidemic. The personal and social burden imposed by diabetes will increase in the close future as its prevalence is expected to double in the next 15–20 years. Type 2 diabetes is caused by the combination of resistance to insulin action and inadequate insulin secretion. Despite the role of profound changes in individual environmental exposure is incontrovertible, several findings clearly indicate that type 2 diabetes and insulin resistance are also heritable. Among the several inhibitors of insulin signalling, which have been recently proposed as determinants of insulin resistance, is TRIB3, a mammalian tribbles homolog which affects insulin signalling at the level of Akt-2, a key modulator of insulin action in target cells. We here report data on a prevalent Q84R TRIB3 missense single nucleotide polymorphism (rs2295490) we first described few years ago. Several lines of evidences indicate that this amino-acid change is, in fact, a gain of function mutation with the potential to affect insulin signalling and thus, to increase the risk of insulin resistance and related clinical outcomes.

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Acknowledgments

This work was partly supported by Italian Ministry of Health (Ricerca Corrente 2006 and 2008 to S.P.).

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Authors and Affiliations

  1. CSS-Mendel Institute, Viale Regina Margherita 261, 00198, Rome, Italy

    Sabrina Prudente, Eleonora Morini & Vincenzo Trischitta

  2. Research Unit of Diabetes and Endocrine Diseases, CSS Scientific Institute, San Giovanni Rotondo, Italy

    Sabrina Prudente & Vincenzo Trischitta

  3. Department of Clinical Sciences, “Sapienza” University, Rome, Italy

    Eleonora Morini

  4. Department of Medical Pathophysiology, “Sapienza” University, Rome, Italy

    Vincenzo Trischitta

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  1. Sabrina Prudente
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  2. Eleonora Morini
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Correspondence to Sabrina Prudente.

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Prudente, S., Morini, E. & Trischitta, V. The emerging role of TRIB3 as a gene affecting human insulin resistance and related clinical outcomes. Acta Diabetol 46, 79–84 (2009). https://doi.org/10.1007/s00592-008-0087-y

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  • DOI: https://doi.org/10.1007/s00592-008-0087-y

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