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Sitagliptin,sitagliptin and metformin,or sitagliptin and amitriptyline attenuate streptozotocin-nicotinamide induced diabetic neuropathy in rats

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The Journal of Biomedical Research 2012年第3期26卷 200-210页

作者： Ashish Kumar Sharma Akash Sharma Rita Kumari Kunal Kishore Divya Sharma Bharthu Parthsarthi Srinivasan Ashok Sharma Santosh Kumar Singh Samir Gaur Vijay Singh Jatav Prashant Sharma Varnika Srivastava Sneha joshi megha joshi Prashant Kumar Dhakad Davender Singh Kanawat Akanksha Mishra Anil Sharma Dharmendra Singh Ravinder Pal Singh Himmat Singh Chawda Rambir Singh Sachin Kumar Raikwar Muneem Kumar Kurmi Pankaj Khatri Ashutosh Agarwal Arshee Munajjam Department of Pharmacology Gyan Vihar School of PharmacySuresh Gyan Vihar UniversityJagatpuraJaipur(Rajasthan)302025India Department of Pharmacology Delhi Institute of Pharmaceutical Sciences&ResearchPushpviharNew Delhi 110017India Department of Pharmacology Kota Collage of PharmacyRIICO Industrial AreaRanpurKota(Rajasthan)Pincode 302025India

Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neu- ropathy, and thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced with nicotinamide- streptozotocin. Drug treatment was initiated on the d 15, with the combination regimen of metformin, pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to significantly im- proved glycemic control, increased grip strength and paw jumping response on d 21, 28 and 35 （P 〈 0.001）. Signif- icant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21, 28 and 35 （P 〈 0.001）. Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells, while administration of metformin and sitagliptin showed tissue regen- eration and no body weight gain. In conclusion, treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain, but causes an increase in grip strength and pain sensitivity, exhibits neural protection, and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes.

关键词： diabetic neuropathy nicotinamide-streptozotocin metformin pioglitazone glimipiride sitagliptin amitriptyline

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