Animal model of gestational diabetes mellitus with pathophysiological resemblance to the human condition induced by multiple factors (nutritional, pharmacological, and stress) in rats

• Main Authors: Abdul Aziz, Siti Hajar, John, Cini Mathew, Mohamed Yusof, Nur Intan Saidaah, Nordin, Massita, Ramasamy, Rajesh, Adam, Aishah, Mohd Fauzi, Fazlin
• Format: Article
• Language: English
• Published: Hindawi Publishing Corporation 2016
• Online Access: http://psasir.upm.edu.my/id/eprint/55066/1/Animal%20Model%20of%20Gestational%20Diabetes%20Mellitus.pdf; http://psasir.upm.edu.my/id/eprint/55066/

This study attempts to develop an experimental gestational diabetes mellitus (GDM) animal model in female Sprague-Dawley rats. Rats were fed with high fat sucrose diet, impregnated, and induced with Streptozotocin and Nicotinamide on gestational day 0 (D0). Sleeping patterns of the rats were also manipulated to induce stress, a lifestyle factor that contributes to GDM. Rats were tested for glycemic parameters (glucose, C-peptide, and insulin), lipid profiles (total cholesterol, triglycerides, HDL, and LDL), genes affecting insulin signaling (IRS-2, AKT-1, and PCK-1), glucose transporters (GLUT-2 and GLUT-4), proinflammatory cytokines (IL-6, TNF-α), and antioxidants (SOD, CAT, and GPX) on D6 and D21. GDM rats showed possible insulin resistance as evidenced by high expression of proinflammatory cytokines, PCK-1 and CRP. Furthermore, low levels of IRS-2 and AKT-1 genes and downregulation of GLUT-4 from the initial to final phases indicate possible defect of insulin signaling. GDM rats also showed an impairment of antioxidant status and a hyperlipidemic state. Additionally, GDM rats exhibited significantly higher body weight and blood glucose and lower plasma insulin level and C-peptide than control. Based on the findings outlined, the current GDM animal model closely replicates the disease state in human and can serve as a reference for future investigations.