Bachelor Program of Senior Services, College of Humanities and Social Sciences, Southern Taiwan University of Science and Technology, Yong Kang, Tainan City, 71005, Taiwan.
Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8520, Japan; Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, 71003, Taiwan.
Biomed Pharmacother. 2018 May;101:155-161. doi: 10.1016/j.biopha.2018.02.084. Epub 2018 Feb 24.
Animal models are widely used to develop drugs for treating diabetes mellitus (DM). Insulin resistance (IR) is one of the main problems in type-2 DM (T2DM). Streptozotocin (STZ) is used to damage pancreatic cells for induction of DM. Many rat models were applied in research as T2DM. However, the degree of IR in each model is unknown. In the present study, IR and insulin signaling were compared in four models of type 2 diabetes: rats fed a fructose-rich chow for 8 weeks, rats feed high-fat chow for 4 weeks followed by injection with streptozotocin (35 mg/kg, i.p.), rats injected with a single low dose streptozotocin (45 mg/kg, i.p.), and rats injected with a single dose of nicotinamide followed by a single high dose of streptozotocin (60 mg/kg, i.p.). Values from these determinations in diabetic rats showing the order that insulin resistance is most marked in rats received fructose-rich chow followed by high-fat diet before STZ injection induced model (HFD/STZ rats), and rats injected with low dose of STZ but it is less marked in rats induced by nicotinamide and STZ. Additionally, insulin secretion was reduced in three rat models except the rats receiving fructose-rich chow. Western blots also showed the same changes in phosphorylation of IRS-1 or Akt using soleus muscle from each model. The obtained data suggest a lack of pronounced IR in the rats with acute diabetes induced by nicotinamide and STZ while IR is markedly identified in rats fed fructose-rich chow. However, the increase of plasma glucose levels in fructose-rich chow-fed rats was not so significant as other groups. Therefore, HFD/STZ rats is an appropriate and stable animal model which is analogous to the human T2DM through a combination of high-fat diet with multiple low-dose STZ injections.
动物模型广泛用于开发治疗糖尿病（DM）的药物。胰岛素抵抗（IR）是 2 型糖尿病（T2DM）的主要问题之一。链脲佐菌素（STZ）用于破坏胰腺细胞以诱导糖尿病。许多大鼠模型被应用于研究 2 型糖尿病。然而，每种模型的 IR 程度尚不清楚。在本研究中，比较了四种 2 型糖尿病模型的 IR 和胰岛素信号：8 周喂果糖丰富的饲料的大鼠、4 周喂高脂肪饲料后注射链脲佐菌素（35mg/kg，ip）的大鼠、单次注射低剂量链脲佐菌素（45mg/kg，ip）的大鼠和单次注射烟酰胺后单次注射高剂量链脲佐菌素（60mg/kg，ip）的大鼠。在表现出胰岛素抵抗最明显的顺序的糖尿病大鼠中，这些测定值显示，在高脂肪饮食（HFD）之前用 STZ 注射诱导的模型（HFD/STZ 大鼠）中接受果糖丰富的饲料喂养的大鼠中，胰岛素抵抗最明显，并且在接受低剂量 STZ 注射的大鼠中，但在接受烟酰胺和 STZ 注射的大鼠中，胰岛素抵抗不那么明显。此外，除了接受果糖丰富的饲料的大鼠外，三种大鼠模型的胰岛素分泌均减少。使用每种模型的比目鱼肌的 Western blot 也显示了 IRS-1 或 Akt 磷酸化的相同变化。获得的数据表明，在接受烟酰胺和 STZ 诱导的急性糖尿病的大鼠中，IR 不明显，而在接受果糖丰富的饲料喂养的大鼠中，IR 明显。然而，果糖丰富的饲料喂养的大鼠的血糖水平升高并不像其他组那样显著。因此，HFD/STZ 大鼠是一种合适且稳定的动物模型，通过高脂肪饮食与多次低剂量 STZ 注射相结合，类似于人类 T2DM。
