title: Tributyltin in male mice disrupts glucose homeostasis as well as recovery after exposure: mechanism analysis.
abstract: Organotin compounds such as tributyltin (TBT) and triphenyltin can induce diabetes and insulin resistance. However, the development of diabetes caused by organotins and its underlying mechanisms remain unclear. In the present study, male KM mice were orally administered with TBT (0.5, 5, and 50 μg/kg) once every 3 days for 45 days. Their body weights increased and reached a significant difference compared to the control, and the fasting blood glucose levels were significantly elevated. The fasting levels of serum insulin and adiponectin increased, while glucagon levels decreased in the animals treated with TBT. The expression of the insulin receptor (IR) signaling cascade, including IR, IR substrate, phosphatidylinositol 3-kinase, Akt, and glucose transporter 4, was inhibited both in the skeletal muscle and the liver, which might be a main reason for the hyperglycemia and hyperinsulinemia. After removing the TBT stress for 60 days, the animals which had received exposure to TBT could recover normoglycemia, accompanied with a recovery of the suppressed IR signal pathway and fasting insulin levels. However, the fasting levels of serum adiponectin and glucagon were lower than that of the control mice, which would remain a potential risk inducing the disruption of glucose homeostasis.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, People's Republic of China.
authors.forename: Bingshui
authors.initials: B
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, People's Republic of China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, People's Republic of China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Xi
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, People's Republic of China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, People's Republic of China. cgwang@xmu.edu.cn.|State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, People's Republic of China. cgwang@xmu.edu.cn.
authors.forename: Chonggang
authors.identifier: http://orcid.org/0000-0002-7605-5898
authors.initials: C
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects*; D006728:Hormones / Q000097:blood; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014220:Trialkyltin Compounds / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D014220:Trialkyltin Compounds; C011559:tributyltin; D005934:Glucagon; D005947:Glucose
keywords: Diabetes; Glucagon; Insulin receptor pathway; Mechanism; Organotins