title: Animal Model of Gestational Diabetes Mellitus with Pathophysiological Resemblance to the Human Condition Induced by Multiple Factors (Nutritional, Pharmacological, and Stress) in Rats.
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.
authors.affiliation: Department of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
authors.forename: Siti Hajar
authors.initials: SH
authors.lastname: Abdul Aziz
authors.affiliation: Department of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia; Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.
authors.forename: Cini Mathew
authors.identifier: 0000-0001-5404-6176
authors.initials: CM
authors.lastname: John
authors.affiliation: Department of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
authors.forename: Nur Intan Saidaah
authors.identifier: 0000-0002-6895-2329
authors.initials: NI
authors.lastname: Mohamed Yusof
authors.affiliation: Department of Pharmaceutical and Life Sciences, Faculty of Pharmacy, Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
authors.forename: Massita
authors.initials: M
authors.lastname: Nordin
authors.affiliation: Immunology Unit, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), 43400 Serdang, Selangor Darul Ehsan, Malaysia.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ramasamy
authors.affiliation: Department of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
authors.forename: Aishah
authors.initials: A
authors.lastname: Adam
authors.affiliation: Department of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
authors.forename: Fazlin
authors.identifier: 0000-0001-5786-2523
authors.initials: F
authors.lastname: Mohd Fauzi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001786:Blood Glucose; D016207:Cytokines / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000235:genetics / Q000473:pathology; D016640:Diabetes, Gestational / Q000097:blood* / Q000235:genetics / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D011247:Pregnancy; D051381:Rats; D012307:Risk Factors
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin