Laboratorio de Investigación en Bioquímica Aplicada, Sección de Estudios de Posgrado e Investigación y Departamento de Formación Básica Disciplinaria, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas,Miguel Hidalgo, Ciudad de México, México.
Departamento de Patología, Instituto de Servicios Periciales y Ciencias Forenses, Tribunal Superior de Justicia de la Ciudad de México, Ciudad de México, México.
Islets. 2022 Dec 31;14(1):114-127. doi: 10.1080/19382014.2022.2051991.
The prevalence of diabetes is rapidly increasing. The current number of diagnosed cases is 422 million, expected to reach 640 million by 2040. Type 2 diabetes, which constitutes 95% of the cases, is characterized by insulin resistance and a progressive loss of β-cell function. Despite intense research efforts, no treatments are yet able to cure the disease or halt its progression. Since all existing animal models of type 2 diabetes have serious drawbacks, one is needed that represents the complete pathogenesis, is low cost and non-obese, and can be developed relatively quickly. The aim of this study was to evaluate a low-cost, non-obese model of type 2 diabetes engendered by administering a daily high dose of tacrolimus (an immunosuppressant) to Wistar rats for 4 weeks. The biochemical and antioxidant markers were measured at basal and after the 4-week tacrolimus treatment. At week 4, the values of these parameters closely resembled those observed in human type 2 diabetes, including fasting blood glucose at 141.5 mg/dL, blood glucose greater than 200 mg/dL at 120 min of the glucose tolerance test, blood glucose at varied levels in the insulin tolerance test, and elevated levels of cholesterol and triglyceride. The tacrolimus treatment produced hypoinsulinemia and sustained hyperglycemia, probably explained by the alteration found in pancreatic β-cell function and morphology. This model should certainly be instrumental for evaluating possible type 2 diabetes treatments, and for designing new immunosuppressants that do not cause pancreatic damage, type 2 diabetes, or new-onset diabetes after transplantation (NODAT).
糖尿病的患病率正在迅速上升。目前已确诊的病例数为 4.22 亿,预计到 2040 年将达到 6.4 亿。其中 95%为 2 型糖尿病,其特征为胰岛素抵抗和β细胞功能的进行性丧失。尽管进行了大量的研究工作,但目前尚无治疗方法能够治愈该疾病或阻止其进展。由于所有现有的 2 型糖尿病动物模型都存在严重缺陷,因此需要一种能够代表完整发病机制、成本低廉、非肥胖且相对快速开发的模型。本研究旨在评估一种通过每天给 Wistar 大鼠高剂量他克莫司(一种免疫抑制剂)治疗 4 周而产生的低成本、非肥胖 2 型糖尿病模型。在基础状态和 4 周他克莫司治疗后测量生化和抗氧化标志物。在第 4 周时,这些参数的值与人类 2 型糖尿病观察到的值非常相似,包括空腹血糖为 141.5mg/dL,葡萄糖耐量试验 120 分钟时血糖大于 200mg/dL,胰岛素耐量试验中血糖水平不同,以及胆固醇和甘油三酯水平升高。他克莫司治疗导致胰岛素血症和持续高血糖,可能是由于发现胰腺β细胞功能和形态发生改变所致。这种模型对于评估可能的 2 型糖尿病治疗方法以及设计新的免疫抑制剂肯定是有用的,这些免疫抑制剂不会引起胰腺损伤、2 型糖尿病或移植后新发糖尿病(NODAT)。
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