Khadke Suresh P, Kuvalekar Aniket A, Harsulkar Abhay M, Mantri Nitin
Interactive Research School for Health Affairs, Bharati Vidyapeeth Deemed University, Katraj, Pune, Maharashtra 411043, India.
Department of Pharmaceutical Biotechnology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune, Maharashtra 411038, India.
Biomedicines. 2019 Sep 27;7(4):76. doi: 10.3390/biomedicines7040076.
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired insulin action and its secretion. The objectives of the present study were to establish an economical and efficient animal model, mimicking pathophysiology of human T2DM to understand probable molecular mechanisms in context with lipid metabolism. In the present study, male Wistar rats were randomly divided into three groups. Animals were fed with high fat diet (HFD) except healthy control (HC) for 12 weeks. After eight weeks, intra peritoneal glucose tolerance test was performed. After confirmation of glucose intolerance, diabetic control (DC) group was injected with streptozotocin (STZ) (35 mg/kg b.w., i.p.). HFD fed rats showed increase ( ≤ 0.001) in glucose tolerance and HOMA-IR as compared to HC. Diabetes rats showed abnormal ( ≤ 0.001) lipid profile as compared to HC. The hepatocyte expression of transcription factors and and their target genes were found to be upregulated, while and expressions were downregulated as compared to the HC. A number of animal models have been raised for studying T2DM, but the study has been restricted to only the biochemical level. The model is validated at biochemical, molecular and histopathological levels, which can be used for screening new therapeutics for the effective management of T2DM.
2型糖尿病(T2DM)是一种以胰岛素作用及其分泌受损为特征的代谢紊乱疾病。本研究的目的是建立一种经济高效的动物模型,模拟人类T2DM的病理生理学,以了解与脂质代谢相关的可能分子机制。在本研究中,雄性Wistar大鼠被随机分为三组。除健康对照组(HC)外,其余动物均喂食高脂饮食(HFD)12周。八周后,进行腹腔内葡萄糖耐量试验。在确认葡萄糖不耐受后,糖尿病对照组(DC)注射链脲佐菌素(STZ)(35mg/kg体重,腹腔注射)。与HC相比,喂食HFD的大鼠葡萄糖耐量和HOMA-IR增加(≤0.001)。与HC相比,糖尿病大鼠血脂谱异常(≤0.001)。与HC相比,发现转录因子和及其靶基因的肝细胞表达上调,而和表达下调。已经建立了许多用于研究T2DM的动物模型,但研究仅限于生化水平。该模型在生化、分子和组织病理学水平上得到验证,可用于筛选有效管理T2DM的新疗法。