• Eugénie Delile, Rémi Nevière, Pierre-Alain Thiébaut, Julie Maupoint, Paul Mulder, David Coquerel, Sylvanie Renet, Jennifer Rieusset, Vincent Richard, and Fabienne Tamion.
• *Normandie Univ, UNIROUEN, Inserm (Institut National de la Santé et de la Recherche Médicale) U1096, Rouen, France †Lille University, LIRIC INSERM U995/Team "Glycation: From Inflammation to Aging," Lille, France ‡Inserm (Institut National de la Santé et de la Recherche Médicale) U1060, Lyon, France §Rouen University Hospital Department of Intensive Care, Rouen, France.
• Shock. 2017 Sep 1; 48 (3): 355-363.

AbstractHyperglycemia is a common feature of septic patients and has been associated with poor outcome and high mortality. In contrast, insulin has been shown to decrease mortality and to prevent the incidence of multiorgan failure but is often associated with deleterious hypoglycemia. Protein Tyrosine Phosphatase 1B (PTP1B) is a negative regulator of both insulin signaling and NO production, and has been shown to be an aggravating factor in septic shock. To evaluate the potential therapeutic effect of PTP1B blockade on glucose metabolism and insulin resistance in an experimental model of sepsis, we assessed the effect of PTP1B gene deletion in a cecal ligation and puncture (CLP) model of sepsis. PTP1B gene deletion significantly limited CLP-induced insulin resistance, improved AMP-activated protein kinase signaling pathway and Glucose Transporter 4 translocation, and decreased inflammation. These effects were associated with a reduction of sepsis-induced endothelial dysfunction/impaired NO production and especially of insulin-mediated dilatation. This modulation of insulin resistance may contribute to the beneficial effect of PTP1B blockade in septic shock, especially in terms of inflammation and cardiac metabolism.

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