title: Oxytocin Protects against Stress-Induced Cell Death in Murine Pancreatic β-Cells.
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.
authors.affiliation: Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Fan-Yan
authors.initials: FY
authors.lastname: Wei
authors.affiliation: Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Matsunaga
authors.affiliation: Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Nanami
authors.initials: N
authors.lastname: Matsunaga
authors.affiliation: Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Kaitsuka
authors.affiliation: Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tomizawa
mesh_terms: D000818:Animals; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010120:Oxytocics / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism*; D018045:Receptors, Oxytocin / Q000172:deficiency; D013312:Stress, Physiological
chemical_list: D010120:Oxytocics; D018045:Receptors, Oxytocin; D010121:Oxytocin