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Activation of the HIF1α/PFKFB3 stress response pathway in beta cells in type 1 diabetes – published online 13/11/2019

Fig from Nomoto paper

Hiroshi Nomoto, Lina Pei, Chiara Montemurro, Madeline Rosenberger, Allison Furterer, Giovanni Coppola, Brian Nadel, Matteo Pellegrini, Tatyana Gurlo, Peter C. Butler, Slavica Tudzarova

Prospective studies of individuals at high risk of type 1 diabetes established that the interval between initiation of beta cell autoimmunity and diabetes onset can be up to 10 years. In this issue, Nomoto, Pei and colleagues ( investigated whether activation of the hypoxia inducible factor 1 α (HIF1α) signalling pathway plays a role in this prolonged prediabetes phase. Evaluation of residual beta cells from individuals with recent-onset and pre-type 1 diabetes revealed activation of a highly conserved pro-survival injury response program initiated by HIF1α, as recently also shown in beta cells in type 2 diabetes. According to the authors, the unexplained slow rate of beta cell attrition but early attenuation of glucose-induced insulin secretion in evolving type 1 diabetes is likely to be due, at least in part, to activation of pro-survival signalling pathways at the expense of beta cell function. They conclude that, since HIF1α signalling has an impact on multiple cell functions, observable changes in beta cells in type 1 and type 2 diabetes may be protective rather than mediating cell toxicity, implying that caution should be used when selecting potential therapeutic targets.

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