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

Ashish Kumar Sharma ,Gaur Samir,Singh Rambir,Khatri Pankaj,Sharma Anil,Joshi Sneha,Joshi Megha,Sharma Prashant,Srivastava Varnika,Agarwal Ashutosh,Sharma Divya,Sharma Ashok,Kishore Kunal,Mishra Akanksha,Munajjam Arshee,Kumari Rita,Himmat Singh Chawda ,Santosh Kumar Singh ,Davender Singh Kanawat ,Ashish Sharma ,Sachin Kumar Raikwar ,B.p Srinivasan ,Ravinder Pal Singh ,Dharmendra Kumar Singh ,Prashant Kumar Dhakad ,Muneem Kumar Kurmi ,Vijay Singh Jatav

doi:10.7555/jbr.26.20110054

Abstract

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.

Highlights

Diabetic neuropathy occurs as a result of damages to the nervous system due to persistent hyperglycemia and can affect many parts of the body including the legs, feet, bladder, heart, gastrointestinal system, and reproductive system
Streptozotocin was purchased from Alexis Biochemicals (San Diego, CA, USA); Nicotinamide was supplied by Ottokemi (Mumbai, India); sitagliptin phosphate (100 mg) was purchased from Merch Sharp and Dohme (Pavia, Italy), amitriptyline hydrochloride (25 mg) from Wockharot Ltd. (Solan, India), metformin hydrochloride (500 mg) from Wallace Pharmaceutical. (Solan, India), pioglitazone hydrochloride (15 mg) from Emcure Pharmaceutical (Pune, India), glimepiride (2 mg) from C
Sitagliptin in combination with metformin or amitriptyline has no effect on the body weight of diabetic rats

Summary

Introduction

Diabetic neuropathy occurs as a result of damages to the nervous system due to persistent hyperglycemia and can affect many parts of the body including the legs, feet, bladder, heart, gastrointestinal system, and reproductive system. The symptoms of diabetic neuropathy include pain, numbness, tingling, or prickling that begins in the feet. Common conditions, which may be associated with diabetic neuropathy, include third nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, polyneuropathy, autonomic neuropathy, and thoracoabdominal neuropathy. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum) in addition to macrovascular conditions that can culminate in diabetic neuropathy[1,2,3]

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