title: Rosiglitazone increases cerebral klotho expression to reverse baroreflex in type 1-like diabetic rats.
abstract: Reduced baroreflex sensitivity (BRS) is widely observed in diabetic human and animals. Rosiglitazone is one of the clinically used thiazolidinediones (TZD) known as PPAR γ agonist. Additionally, the klotho protein produced from choroid plexus in the central nervous system is regulated by PPAR γ . In an attempt to develop the new therapeutic strategy, we treated streptozotocin-induced diabetic rats (STZ) with rosiglitazone (STZ + TZD) orally at 10 mg/kg for 7 days. Also, STZ rats were subjected to intracerebroventricular (ICV) infusion of recombinant klotho at a dose of 3 μ g/2.5 μ L via syringe pump (8 μ g/hr) daily for 7 days. The BRS and heart rate variability were then estimated under challenge with a depressor dose of sodium nitroprusside (50 μ g/kg) or a pressor dose of phenylephrine (8 μ g/kg) through an intravenous injection. Lower expression of klotho in medulla oblongata of diabetic rats was identified. Cerebral infusion of recombinant klotho or oral administration of rosiglitazone reversed BRS in diabetic rats. In conclusion, recovery of the decreased klotho in brain induced by rosiglitazone may restore the impaired BRS in diabetic rats. Thus, rosiglitazone is useful to reverse the reduced BRS through increasing cerebral klotho in diabetic disorders.
authors.affiliation: Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Meng-Fu
authors.identifier: 0000-0002-9093-4477
authors.initials: MF
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, Chi-Mei Medical Center, Yong Kang, Tainan 71004, Taiwan.
authors.forename: Po-Ming
authors.initials: PM
authors.lastname: Ku
authors.affiliation: Department of Neurosurgery, Taipei Medical University-Shuang Ho Hospital, Taipei 23561, Taiwan.
authors.forename: Jia-Wei
authors.identifier: 0000-0002-3311-5379
authors.initials: JW
authors.lastname: Lin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D005966:Glucuronidase / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007276:Injections, Intraventricular; D000090265:Klotho Proteins; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D000077154:Rosiglitazone; D013311:Streptozocin; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D011994:Recombinant Proteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013311:Streptozocin; D005966:Glucuronidase; D000090265:Klotho Proteins