title: Effects of insulin combined with idebenone on blood-brain barrier permeability in diabetic rats.
abstract: This study investigates the effect of insulin combined with idebenone on blood-brain barrier (BBB) permeability in experimental streptozotocin-induced diabetic rats as well as the underlying mechanisms. With a diabetic rat model, we show that insulin and idebenone normalize body weight and water intake and restore BBB permeability and that their combination displays a synergistic effect. The results from transmission electron microscopy show that the combination of insulin and idebenone significantly closed the tight junction (TJ) in diabetic rats. The results from Western blotting in diabetic rats show that the upregulation of TJ-associated proteins occludin, and zonula occludens (ZO)-1 caused by the combination of insulin and idebenone is more remarkable than that with either agent alone. In addition, the activations of reactive oxygen species (ROS) and advanced glycation end products (AGEs) and the expression levels of receptors for advanced glycation end-products (RAGE) and nuclear factor-κB (NF-κB) were significantly decreased after treatment with insulin and idebenone in diabetic rats. These results suggest that the combination of insulin and idebenone could decrease the BBB permeability in diabetic rats by upregulating the expression of occludin, claudin-5, and ZO-1 and that the ROS/AGE/RAGE/NF-κB signal pathway might be involved in the process.
authors.affiliation: Department of Neurobiology, College of Basic Medicine, and Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Yan-Na
authors.initials: YN
authors.lastname: Sun
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Liu
authors.forename: Yi-Xue
authors.initials: YX
authors.lastname: Xue
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D002199:Capillary Permeability / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D046529:Microscopy, Electron, Transmission; D009698:Nucleoproteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D018709:Statistics, Nonparametric; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D007004:Hypoglycemic Agents; D007328:Insulin; D009698:Nucleoproteins; D017382:Reactive Oxygen Species; D014451:Ubiquinone; C036619:idebenone
keywords: blood-brain barrier; diabetes; idebenone; insulin; tight junction