title: Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia.
abstract: Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the decrease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance.
authors.affiliation: Department of Nutrition, Affiliated Dongfang Hospital of Tongji University, Shanghai 200120, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Shu
authors.affiliation: Department of Nutrition, First Affiliated Hospital of Guangxi Medical University, Nanning 530027, Guangxi Zhuang Autonomous Region, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nutrition, Affiliated Dongfang Hospital of Tongji University, Shanghai 200120, China.
authors.forename: Han
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Nutrition, Affiliated Dongfang Hospital of Tongji University, Shanghai 200120, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Kang
authors.affiliation: Department of Nutrition, Affiliated Changhai Hospital of the Second Military Medical University of Chinese PLA, Shanghai 200433, China.
authors.forename: Donglian
authors.initials: D
authors.lastname: Cai
keywords: brain injury; brain-derived neurotrophic factor; cerebral ischemia/reperfusion injury; cerebral ischemic stress; diabetes mellitus; glucose intolerance; grants-supported paper; hyperglycemia; hypothalamus; insulin receptor; neural regeneration; neuroregeneration