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Glucose regulation of islet stress responses and beta-cell failure in type 2 diabetes.

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Jonas, Jean-Christophe [UCL] Bensellam, Mohammed [UCL] Duprez, Jessica [UCL] Elouil, Hajar [UCL] Guiot, Yves [UCL] Pascal, Séverine [UCL]

Pancreatic beta-cells exposed to high glucose concentrations display altered gene expression, function, survival and growth that may contribute to the slow deterioration of the functional beta-cell mass in type 2 diabetes. These glucotoxic alterations may result from various types of stress imposed by the hyperglycaemic environment, including oxidative stress, endoplasmic reticulum stress, cytokine-induced apoptosis and hypoxia. The glucose regulation of oxidative stress-response and integrated stress-response genes in cultured rat islets follows an asymmetric V-shaped profile parallel to that of beta-cell apoptosis, with a large increase at low glucose and a moderate increase at high vs. intermediate glucose concentrations. These observations suggest that both types of stress could play a role in the alteration of the functional beta-cell mass under states of prolonged hypoglycaemia and hyperglycaemia. In addition, beta-cell demise under glucotoxic conditions may also result from beta-cell hypoxia and, in vivo, from their exposure to inflammatory cytokines released locally by non-endocrine islet cells. A better understanding of the relative contribution of each type of stress to beta-cell glucotoxicity and of their pathophysiological cause in vivo may lead to new therapeutic strategies to prevent the slow deterioration of the functional beta-cell mass in glucose intolerant and type 2 diabetic patients.

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Bibliographic reference Jonas, Jean-Christophe ; Bensellam, Mohammed ; Duprez, Jessica ; Elouil, Hajar ; Guiot, Yves ; et. al. Glucose regulation of islet stress responses and beta-cell failure in type 2 diabetes.. In: Diabetes, obesity & metabolism, Vol. 11 Suppl 4, p. 65-81 (2009)
Permanent URL http://hdl.handle.net/2078.1/27373