The main objective of the study was to develop an alternative non-genetic rat model for type 2 diabetes (T2D). Six-week-old male Sprague-Dawley rats (190.56 ± 23.60 g) were randomly divided into six groups, namely: Normal Control (NC), Diabetic Control (DBC), Fructose-10 (FR10), Fructose-20 (FR20), Fructose-30 (FR30) and Fructose-40 (FR40) and were fed a normal rat pellet diet ad libitum for 2 weeks. During this period, the two control groups received normal drinking water whilst the fructose groups received 10, 20, 30 and 40% fructose in drinking water ad libitum, respectively. After two weeks of dietary manipulation, all groups except the NC group received a single injection (i.p.) of streptozotocin (STZ) (40 mg/kg b.w.) dissolved in citrate buffer (pH 4.4). The NC group received only a vehicle buffer injection (i.p.). One week after the STZ injection, animals with non-fasting blood glucose levels > 300 mg/dl were considered as diabetic. Three weeks after the STZ injection, the animals in FR20, FR30 and FR40 groups were eliminated from the study due to the severity of diabetes and the FR10 group was selected for the remainder of the 11 weeks experimental period. The significantly (p < 0.05) higher fluid intake, blood glucose, serum lipids, liver glycogen, liver function enzymes and insulin resistance (HOMA-IR) and significantly (p < 0.05) lower body weight, oral glucose tolerance, number of pancreatic β-cells and pancreatic β-cell functions (HOMA-β) of FR10 group demonstrate that the 10% fructose-fed followed by 40 mg/kg of BWSTZ injected rat can be a new and alternative model for T2D.
Diabetes is one of the major global public health problems and is gradually getting worse particularly in developing nations where 95% of patients are suffering from type 2 diabetes (T2D). Animal models in diabetes research are very common where rodents are the best choice of use due to being smaller in size, easy to handle, omnivorous in nature, and non-wild tranquil behavior. Normally rodent models are classified into two major classes namely: (1) genetic or spontaneously induced models and (2) non-genetic or experimentally induced models. Non-genetic models are more popular compared to genetic models due to lower cost, wider availability, easier to induce diabetes, and of course easier to maintain compared to genetic models. A number of non-genetic models have been developed in last three decades for diabetes research including adult alloxan/streptozotocin (STZ) models, partial pancreatectomy model, high-fat (HF) diet-fed models, fructose-fed models, HF diet-fed STZ models, nicotinamide-STZ models, monosodium-glutamate (MSG) induced models, and intrauterine growth retardation (IUGR) models. A T2D model should have the all major pathogenesis of the disease usually found in humans; however, none of the above-mentioned models are without limitations. This chapter comparatively evaluates most of the experimentally induced rodent models of T2D with their limitations, advantages, disadvantages, and criticality of development in order to help diabetes research groups to more appropriately select the animal models to work on their specific research question.
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