Neuregulin 1 treatment improves glucose tolerance in diabetic db/db mice, but not in healthy mice

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.

Keywords:

• NRG1
• insulin
• glucose
• diabetes
• hepatic

Acknowledgements

rhNRG1 was kindly provided by Zensun Sci & Tech Ltd. The authors wish to thank Chistophe Del’homme, Catherine Besson and Philippe Denis for animal husbandry and skillful technical assistance, and Elisabetta Andermarcher for language help and writing assistance.

Disclosure statement

Xinyan Li is employed by Zensun Sci & Tech Ltd.