Oxytocin Protects against Stress-Induced Cell Death in Murine Pancreatic β-Cells

Sayaka Watanabe, Fan Yan Wei, Tomomi Matsunaga, Nanami Matsunaga, Taku Kaitsuka, Kazuhito Tomizawa

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Oxytocin (Oxt) is a key neuropeptide that regulates maternal behaviors as well as social behaviors in mammals. Interestingly, recent studies have shown that the impairment of Oxt signaling is associated with the disturbance of metabolic homeostasis, resulting in obesity and diabetes. However, the molecular mechanism by which Oxt signaling controls metabolic responses is largely unknown. Here, we report that Oxt signaling attenuates the death of pancreatic beta cells in islets exposed to cytotoxic stresses. The protective effect of Oxt was diminished in islets isolated from oxytocin receptor knockout (Oxtr-/-) mice. Oxtr-/- mice developed normally, but exhibited impaired insulin secretion and showed glucose intolerance under a high-fat diet. Mechanistically, the deficiency of Oxtr impaired MAPK/ERK-CREB signaling, which exaggerated the endoplasmic reticulum stress response and ultimately increased the death of beta cells in pancreatic islets under stressed conditions. These results reveal that Oxt protects pancreatic beta cells against death caused by metabolic stress, and Oxt signaling may be a potential therapeutic target.

Original languageEnglish
Article number25185
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - May 4 2016
Externally publishedYes

ASJC Scopus subject areas

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    Watanabe, S., Wei, F. Y., Matsunaga, T., Matsunaga, N., Kaitsuka, T., & Tomizawa, K. (2016). Oxytocin Protects against Stress-Induced Cell Death in Murine Pancreatic β-Cells. Scientific Reports, 6, [25185]. https://doi.org/10.1038/srep25185