Wednesday , 20 September 2017

Preclinical safety, toxicology and efficacy studies of Recombinant Exendin-4 (Antidaibetic peptide) on wistar rats

U. Venkatesh1*, Sri Rama Radha1, P. Suresh1, G. Sravan Reddy2
1St John’s College of Pharmacy, Yemmiganur, Kurnool, Andhra Pradesh
2Hi-Q Herbals, Kothapet, Hyderabad, Telangana

Recombinant Exendin-4 is a 39 amino acid peptide which exhibits sequence identity over 30 amino acids with mammalian glucagon like peptide-1 (GLP-1) and shares many of the gluco-regulatory actions observed with GLP-1. It enhances glucose dependent insulin secretion in the pancreatic beta-cells by suppressing inappropriately elevated glucagon secretion, and slows down the process of gastric emptying in the gut. Unlike GLP-1, Recombinant Exendin-4 exhibit extended kinetics due to its resistance to proteolytic degradation by dipeptidyl peptidase IV (DPP-I). The present study was performed to investigate the efficacy of recombinant Exendin-4 in Albino wister rats. The Efficacy of the Antidiabetic recombinant product was assessed on the high fat diet fed hyperglycemic animals. For this study animals are selected and divided into 4 groups (each group consists of 3 male and 3 female) in which 2 groups of Animals were fed with high fat diet and other 2 groups of animals fed with low fat diet for a period of 4 weeks , only two groups (LFD & HFD) treated with multiple low doses of STZ (30 mg/kg IP at weekly interval for 2 weeks) produced frank hyperglycemia in HFD-fed rats with highly successful rate, after attaining the hyperglycemia the animals ﴾2 groups i.e LFD+ recombinant Exendin-4, HFD+ recombinant Exendin-4, in which one receives the low fat diet and another one receives the high fat diet ) were exposed to test drug for a period of 6 weeks along with their diets and assessed their metabolic parameters such as Glucose tolerance test (GTT),Triglyceride levels and blood glucose levels & plasma insulin levels after administering the recombinant Exendin-4 daily subcutaneously twice daily for a period of 6 weeks. The result of this experiment clearly indicates that, recombinant Exendin-4 corrected the hyperglycemia & hyperinsulinemia in high fat fed animals in comparison with low fat fed animals.
Keywords: Exendin-4, Amino acid peptide, GLP-1, DPP-IV,HFD, LFD, STZ, albino wister rats, Haematology.

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