%0 Journal Article %A Roberto Bianchi %A Ilaria Cervellini %A Carla Porretta-Serapiglia %A Norberto Oggioni %A Byan Burkey %A Pietro Ghezzi %A Guido Cavaletti %A Giuseppe Lauria %T Beneficial effects of PKF275-055, a novel, selective, and orally bioavailable, long-acting dipeptidyl peptidase IV inhibitor in streptozotocin-induced diabetic peripheral neuropathy %D 2011 %R 10.1124/jpet.111.181529 %J Journal of Pharmacology and Experimental Therapeutics %P jpet.111.181529 %X PKF275-055, a vildagliptin analog, is a novel, selective, potent, orally bioavailable, long-acting dipeptidyl peptidase IV inhibitor. We studied the effect of PKF275-055 administration in the prevention, protection or treatment of diabetic neuropathy in streptozotocin-induced diabetic rat. PKF275-055 improved body and muscle weight. Oral glucose tolerance tests showed a marked improvement in glucose metabolism under all the treatment schedules. When tested in prevention and protection experiments, PKF275-055 completely averted the decrease in Na+/K+-ATPase activity, and partially counteracted the nerve conduction velocity (NCV) deficit observed in untreated diabetic rats but had no effects on abnormal mechanical and thermal sensitivity. When used in a therapeutic setting, PKF275-055 induced a significant correction in the alteration in Na+,K+-ATPase activity and NCV present in untreated diabetics. Diabetic rats develop mechanical hyperalgesia within two weeks after STZ-injection and exhibit significantly longer thermal response latencies. Importantly, PKF275-055 treatment restored mechanical sensitivity thresholds by about 50% (p < 0.01) and progressively improved the alteration in thermal responsiveness. In conclusion, PKF275-055 showed an anabolic effect, improved oral glucose tolerance, and counteracted the alterations in Na+,K+-ATPase activity, NCV and nociceptive thresholds in diabetic rats. The present data support a potential therapeutic effect of PKF275-055 in the treatment of diabetic neuropathy. %U https://jpet.aspetjournals.org/content/jpet/early/2011/10/07/jpet.111.181529.full.pdf