title: Treatment of streptozotocin-induced diabetic rats with alogliptin: effect on vascular and neural complications.
abstract: We sought to determine the effect of dipeptidyl peptidase IV (DPP-IV) inhibition on streptozotocin diabetes-induced vascular and neural dysfunction. After 4 weeks of untreated diabetes, rats were treated for 12 weeks with Alogliptin (DPP-IV inhibitor). Diabetes caused a slowing of motor and sensory nerve conduction velocity, thermal hypoalgesia, reduction in intraepidermal nerve fiber density in the hindpaw, and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles. Treatment significantly improved motor nerve conduction velocity and thermal response latency. Sensory nerve conduction velocity was marginally improved with treatment of diabetic rats, and treatment did not improve the decrease in intraepidermal nerve fiber density. Vascular relaxation by epineurial arterioles to calcitonin gene-related peptide but not acetylcholine was significantly improved with treatment. These studies suggest that some but not all vascular and neural complications associated with type 1 diabetes can be improved with the inhibition of DPP-IV activity.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Davidson
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Coppey
authors.forename: Brian
authors.initials: B
authors.lastname: Dake
authors.forename: Mark A
authors.initials: MA
authors.lastname: Yorek
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects; D013997:Time Factors; D014498:Uracil / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010880:Piperidines; D014498:Uracil; C520853:alogliptin