Animal Model of Gestational Diabetes Mellitus with Pathophysiological Resemblance to the Human Condition Induced by Multiple Factors (Nutritional, Pharmacological, and Stress) in Rats.

Siti Hajar Abdul Aziz,Aishah Adam,Massita Nordin,Nur Intan Saidaah Mohamed Yusof,Rajesh Ramasamy,Fazlin Mohd Fauzi,Cini Mathew John

doi:10.1155/2016/9704607

Abstract

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.

Highlights

Gestational diabetes mellitus (GDM), a common pregnancy complication, is defined by the American Diabetes Association as diabetes that is not clearly apparent diabetes, diagnosed in the second or third trimester of pregnancy [1]
The GDM animal model showed signs of insulin resistance where expressions of both proinflammatory cytokines (IL-6 and TNF-α), PCK-1, and serum CRP level were higher than control
Low concentration of IRS-2 genes and AKT-1 and reduced level of GLUT-4 from the initial to final phases indicate the possible defect of insulin signaling in our GDM animal model

Summary

Introduction

Gestational diabetes mellitus (GDM), a common pregnancy complication, is defined by the American Diabetes Association as diabetes that is not clearly apparent diabetes, diagnosed in the second or third trimester of pregnancy [1]. Resistance to insulin escalates to increase the glucose supply to the fetus. Pancreatic beta cells compensate for the increased demand in glucose, and a normoglycemic state is maintained. Women who develop GDM have deficits in beta cells response leading to insufficient insulin secretion, leading to a state of hyperglycemia [2, 3]. This insulin resistance seen in GDM is similar to that observed in Type 2 diabetes mellitus (T2DM). When beta cells are no longer able to compensate for the insulin resistance, this leads to glucose intolerance.

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Conclusion