Department of Biochemistry and Microbiology, University of Zululand, Private Bag X1001, KwaDlangezwa, 3886, South Africa.
Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg, 7505, South Africa.
BMC Complement Altern Med. 2018 Oct 1;18(1):265. doi: 10.1186/s12906-018-2337-z.
A substantial literature supports antidiabetic properties of the lanosteryl triterpene (methyl-3β-hydroxylanosta-9,24-dien-21-oate, RA-3) isolated from Protorhus longifolia stem bark. However, the molecular mechanism(s) associated with the antihyperglycemic properties of the triterpene remained to be explored. The current study aimed at investigating the molecular mechanism(s) through which RA-3 improves insulin signaling in streptozotocin-induced type 1 diabetic rats.
The type 1 diabetic rats were treated daily with a single oral dose of RA-3 (100 mg/kg) for 28 days. The rats were then sacrificed, and blood, skeletal muscle and pancreases were collected for biochemical, protein expression and histological analysis, respectively.
Persistently high blood glucose levels in the diabetic control rats significantly increased expression of IRS-1 while the expression of p-Akt , p-GSK-3β , GLUT 4 and GLUT 2 were decreased. However, enhanced muscle insulin sensitivity, which was indicated by a decrease in the expression of IRS-1 with a concomitant increase in the p-Akt, p-GSK-3β , GLUT 4 and GLUT 2 expression were observed in the diabetic rats treated with RA-3. The triterpene-treated animals also showed an improved pancreatic β-cells morphology, along with increased C-peptide levels. An increase in the levels of serum antioxidants such as catalase, superoxide dismutase, and reduced glutathione was noted in the rats treated with the triterpene, while their serum levels of interleukin-6 and malondialdehyde were reduced.
It is apparent that RA-3 is able to improve the insulin signaling in type 1 diabetic rats. Its beta (β)-cells protecting mechanism could be attributed to its ability to alleviate inflammation and oxidative stress in the cells.
从 Protorhus longifolia 茎皮中分离得到的羊毛甾烷三萜（甲基-3β-羟基羊毛甾-9,24-二烯-21-酸，RA-3）具有抗糖尿病作用，这方面已有大量文献报道。然而，该三萜具有降血糖作用的分子机制仍有待探索。本研究旨在探讨 RA-3 改善链脲佐菌素诱导的 1 型糖尿病大鼠胰岛素信号转导的分子机制。
1 型糖尿病大鼠每天口服 RA-3（100mg/kg）一次，连续 28 天。然后处死大鼠，采集血液、骨骼肌和胰腺，分别用于生化、蛋白表达和组织学分析。
糖尿病对照组大鼠持续高血糖水平显著增加 IRS-1 的表达，而 p-Akt、p-GSK-3β、GLUT4 和 GLUT2 的表达则降低。然而，RA-3 治疗的糖尿病大鼠肌肉胰岛素敏感性增强，表现为 IRS-1 表达降低，同时 p-Akt、p-GSK-3β、GLUT4 和 GLUT2 表达增加。用三萜处理的动物还显示出胰腺β细胞形态得到改善，同时 C 肽水平升高。用三萜处理的大鼠血清抗氧化剂水平如过氧化氢酶、超氧化物歧化酶和还原型谷胱甘肽升高，而血清白细胞介素-6 和丙二醛水平降低。
RA-3 能够改善 1 型糖尿病大鼠的胰岛素信号转导。其β细胞保护机制可能归因于其减轻细胞炎症和氧化应激的能力。
