Gaël Ennequin1,2, Kevin Caillaud1, Vivien Chavanelle1, Allison Teixeira1, Monique Etienne1, Xinyan Li3, Nathalie Boisseau1, Pascal Sirvent1. 1. Clermont Auvergne University, EA 3533, Laboratory of the Metabolic Adaptations to Exercise under Physiological and Pathological Conditions (AME2P), Clermont-Ferrand, France. 2. PEPITE EA4267, and Exercise Performance Health Innovation Platform Univ. Bourgogne Franche-Comté, Besançon, France. 3. Zensun Sci & Tech Ltd, Shanghai, China.
Abstract
Context: Neuregulin 1 (NRG1) and ErbB receptors are involved in glucose homeostasis. However, the effects of the neuregulin 1-ErbB pathway activation on glucose metabolism in liver are controversial.Objective: Assess NRG1 and ErbB signalling in liver and the effects of 8-week treatment with NRG1 on glucose homeostasis in diabetic db/db mice and in control healthy mice. Results: NRG1 improved glucose, insulin and insulin sensitivity index during OGTT in db/db mice, but not in control mice. Compared with healthy mice, phosphorylation of p38, ErbB-1 and ErbB-3 was increased in diabetic mice, and neuregulin 1 treatment increased phosphorylation of p38 and ErbB-4. Conversely, the AKT/FOXO1 pathway was not affected by the 8-week treatment with NRG1. Conclusion: Diabetic mice showed altered NRG1-ErbB pathway in the liver compared with healthy mice. Moreover, chronic NRG1 treatment increased p38 phosphorylation in liver and improved glucose tolerance in diabetic mice, but not in control mice.
Context:Neuregulin 1 (NRG1) and ErbB receptors are involved in glucose homeostasis. However, the effects of the neuregulin 1-ErbB pathway activation on glucose metabolism in liver are controversial.Objective: Assess NRG1 and ErbB signalling in liver and the effects of 8-week treatment with NRG1 on glucose homeostasis in diabetic db/db mice and in control healthy mice. Results:NRG1 improved glucose, insulin and insulin sensitivity index during OGTT in db/db mice, but not in control mice. Compared with healthy mice, phosphorylation of p38, ErbB-1 and ErbB-3 was increased in diabeticmice, and neuregulin 1 treatment increased phosphorylation of p38 and ErbB-4. Conversely, the AKT/FOXO1 pathway was not affected by the 8-week treatment with NRG1. Conclusion:Diabeticmice showed altered NRG1-ErbB pathway in the liver compared with healthy mice. Moreover, chronic NRG1 treatment increased p38 phosphorylation in liver and improved glucose tolerance in diabeticmice, but not in control mice.