Comparative Histoarchitectural and Biochemical Studies of the Hippocampus in Peroxisome Proliferative Activated Receptor Gamma Agonist Treated Insulin Resistant Rats

¹ Department of Biological Sciences, Faculty of Pure and Applied Sciences, Federal University, Wukari, Nigeria.

² Department of Physiology, Faculty of Biomedical Sciences, Kampala International University, Western Campus, P.O. Box 71, Ishaka-Bushenyi, Uganda.

³ Department of Anatomy, Faculty of Basic Medical Sciences, University of Lagos, Nigeria.

⁴ Department of Biochemistry, Faculty of Computing and Applied Sciences, Baze University, Abuja, Nigeria.

⁵ Department of Biological Sciences, Faculty of Science, Yobe State University, Damaturu, Yobe, Nigeria.

⁶ Department of Human Kinetics and Sports Science, Alvan Ikoku Federal College of Education, Owerri, Imo State, Nigeria.

^*Corresponding Author

Ejike Daniel Eze, PhD

Senior Lecturer, Department of Physiology, Kampala International University

Western Campus, P. O. Box 71,

Ishaka - Bushenyi

Uganda

Tel: +256 782975042

E-mail: daneze4@gmail.com

Abstract

Background: The currently prescribed anti-diabetic drugs have been clinically proven to develop resistance to reduce the elevated blood glucose level, reduce haemoglobin A1c (HbA1) concentration, possess insulin insensitivity issues as well as other pharmacokinetic disturbances.

Aim: To evaluate the activity of peroxisome proliferative activated receptor (PPRA) gamma agonist; pioglitazone and fenofibrate treated insulin resistant rats.

Materials and Methods: Apparently healthy male rats were intraperitoneally injected into diabetes with STZ (30 mg/kg b. w.) for five days and fed with diet rich in fat for 8 weeks. Pioglitazone (20 mg/kg b. w.) and fenofibrate (10 mg/kg b. w.) was administered by oral gavage to rats which are obese and resistant to insulin for 15 consecutive days. Over the last 7 days, blood collected intraperitoneally was used to test for glucose and insulin tolerance as well as gluconeogenesis. At the end of 15 days experimental treatment period, blood collected was used for biochemical assay whereas in the liver and skeletal muscle, glucose transporter 4 (GLUT4) and insulin receptor substrate -1 (IRS-1) protein expression were assayed for using immune-histochemistry.

Result: The low-dose STZ and HFD - induced obese rats showed significant (p<0.05) insulin resistance and obesity when compared with the control animals. Treatment of test group animals with 20 mg/kg b. w. of pioglitazone and 10 mg/kg b. w. of fenofibrate statistically (p<0.05) lowered levels of blood insulin, triglyceride and free fatty acid but raised the concentration of high-density lipoprotein-cholesterol (HDL-C). Also, there was appreciable (p<0.05) reduction in lipid content of the liver and muscle following treatment with pioglitazone and fenofibrate. The skeletal muscle GLUT4 count as well as liver and skeletal muscle IRS-1 protein contents were sufficiently (p<0.05) elevated.

Conclusion: Results gathered from the study suggest improved sensitivity of insulin in low-dose STZ and HFD-induced obese rats following treatment with pioglitazone and fenofibrate. The insulin sensitizing activity in the animals by pioglitazone and fenofibrate may be due to inhibition of gluconeogenesis, amelioration of lipid metabolism, reduction in hyperinsulinemia as well as elevation of IRS-1 and GLUT4 protein expression in insulin-sensitive tissues.

Keywords:Type 2 diabetes mellitus, Hippocampus, PPAR-gamma, Pioglitazone, Fenofibrate

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