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单次注射链脲佐菌素(50mg)可诱导大鼠模型产生胰岛素抵抗伴 2 型糖尿病。

Induction of a single dose of streptozotocin (50 mg) in rat model causes insulin resistance with type 2 diabetes mellitus.

机构信息

Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Cheras, 56000, Kuala Lumpur, Malaysia.

Department of Food Sciences with Nutrition, Faculty of Applied Sciences, UCSI University, Cheras, 56000, Kuala Lumpur, Malaysia.

出版信息

Fundam Clin Pharmacol. 2023 Aug;37(4):769-778. doi: 10.1111/fcp.12892. Epub 2023 Mar 17.

Abstract

Streptozotocin (STZ) is a broad-spectrum antibiotic that is toxic to the insulin-producing beta cells of the pancreatic islets. STZ is currently used clinically for the treatment of metastatic islet cell carcinoma of the pancreas and the induction of diabetes mellitus (DM) in rodents. So far, there has been no previous research to show that STZ injection in rodents causes insulin resistance in type 2 diabetes mellitus (T2DM). The purpose of this study was to determine if rats (Sprague-Dawley) developed type 2 diabetes mellitus (insulin resistance) after 72 h of intraperitoneal administration of 50 mg/kg STZ. Rats with fasting blood glucose levels above 11.0 mM, 72 h post-STZ induction, were used. The body weight and plasma glucose levels were measured every week throughout the 60-day treatment period. The plasma, liver, kidney, pancreas, and smooth muscle cells were harvested for antioxidant, biochemical analysis, histology, and gene expression studies. The results revealed that STZ was able to destroy the pancreatic insulin-producing beta cell, as evidenced by an increase in plasma glucose level, insulin resistance, and oxidative stress. Biochemical investigation indicates that STZ can generate diabetes complications through hepatocellular damage, elevated HbA1c, kidney damage, hyperlipidemia, cardiovascular damage, and impairment of the insulin-signaling pathway.

摘要

链脲佐菌素(STZ)是一种广谱抗生素,对胰腺胰岛的胰岛素产生细胞具有毒性。STZ 目前临床上用于治疗胰腺转移胰岛细胞瘤和诱导啮齿动物糖尿病(DM)。到目前为止,还没有研究表明 STZ 注射会在 2 型糖尿病(T2DM)中引起胰岛素抵抗。本研究的目的是确定腹腔内注射 50mg/kg STZ 72 小时后,大鼠(Sprague-Dawley)是否会发展为 2 型糖尿病(胰岛素抵抗)。STZ 诱导后 72 小时空腹血糖水平超过 11.0mM 的大鼠用于实验。在 60 天的治疗期间,每周测量体重和血浆葡萄糖水平。采集血浆、肝脏、肾脏、胰腺和平滑肌细胞进行抗氧化、生化分析、组织学和基因表达研究。结果表明,STZ 能够破坏胰腺胰岛素产生的β细胞,这可以通过血浆葡萄糖水平升高、胰岛素抵抗和氧化应激来证明。生化研究表明,STZ 可以通过肝细胞损伤、HbA1c 升高、肾脏损伤、高血脂、心血管损伤和胰岛素信号通路受损来引发糖尿病并发症。

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