L Yu1, J F Chen2, X Shuai1, Y Xu1, Y Ding1, J Zhang3, W Yang3, X Liang4, D Su5, C Yan6. 1. Department of Pathology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, Jiangsu, China. 2. Department of Endocrinology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China. 3. Department of Laboratory Medicine, Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China. 4. The Center of Metabolic Disease Research, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, Jiangsu, China. 5. Department of Pathology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, Jiangsu, China. sudongming@njmu.edu.cn. 6. Department of Endocrinology, Clinical Medical College of Yangzhou University, Yangzhou, 225001, Jiangsu, China. yancaifeng@126.com.
Abstract
AIM: Artesunate (ART) has been known as the most effective and safe reagents to treat malaria for many years. In this study, we explored whether ART could protect pancreatic beta-cell against cytokine-induced damage. MATERIALS AND METHODS: The production of nitrite (NO) was detected with the Griess Assay Kit. SIRT1 and inducible nitric oxide synthase (iNOS) expression were determined with Western blot. The transcriptional activity of NF-κB was evaluated by luciferase reporter assay. The expression of Sirt1 was silenced by RNA interference. Glucose-stimulated insulin secretion (GSIS) and potassium-stimulated insulin secretion (KSIS) assays were performed to measure the effect of ART on pancreatic beta-cells' function. The effect of ART on beta-cells apoptosis was evaluated by using Hochest/PI staining and TUNEL assay. RESULTS: ART enhanced GSIS (KSIS) and reduced apoptosis of pancreatic beta-cells induced by IL-1β. Further study showed that ART inhibited IL-1β-induced increase of NF-κB activity, iNOS expression, and NO production. Moreover, ART up-regulated SIRT1 expression in INS-1 cells and islets exposed to IL-1β. Inhibition of SIRT1 expression could partially abolished the inhibitory effect of ART on NF-κB activity in IL-1β-treated beta-cells. More importantly, the protective effect of ART on cytokine-induced damage was reversed by silencing SIRT1 expression. CONCLUSIONS: ART can elicit a protective effect on beta-cells exposed to IL-1β by stimulating SIRT1 expression, which resulted in the decrease of NF-κB activity, iNOS expression, and NO production. Hence, ART might be an effective drug for diabetes.
AIM: Artesunate (ART) has been known as the most effective and safe reagents to treat malaria for many years. In this study, we explored whether ART could protect pancreatic beta-cell against cytokine-induced damage. MATERIALS AND METHODS: The production of nitrite (NO) was detected with the Griess Assay Kit. SIRT1 and inducible nitric oxide synthase (iNOS) expression were determined with Western blot. The transcriptional activity of NF-κB was evaluated by luciferase reporter assay. The expression of Sirt1 was silenced by RNA interference. Glucose-stimulated insulin secretion (GSIS) and potassium-stimulated insulin secretion (KSIS) assays were performed to measure the effect of ART on pancreatic beta-cells' function. The effect of ART on beta-cells apoptosis was evaluated by using Hochest/PI staining and TUNEL assay. RESULTS:ART enhanced GSIS (KSIS) and reduced apoptosis of pancreatic beta-cells induced by IL-1β. Further study showed that ART inhibited IL-1β-induced increase of NF-κB activity, iNOS expression, and NO production. Moreover, ART up-regulated SIRT1 expression in INS-1 cells and islets exposed to IL-1β. Inhibition of SIRT1 expression could partially abolished the inhibitory effect of ART on NF-κB activity in IL-1β-treated beta-cells. More importantly, the protective effect of ART on cytokine-induced damage was reversed by silencing SIRT1 expression. CONCLUSIONS:ART can elicit a protective effect on beta-cells exposed to IL-1β by stimulating SIRT1 expression, which resulted in the decrease of NF-κB activity, iNOS expression, and NO production. Hence, ART might be an effective drug for diabetes.
Authors: Thomas Efferth; Marta R Romero; Dana G Wolf; Thomas Stamminger; Jose J G Marin; Manfred Marschall Journal: Clin Infect Dis Date: 2008-09-15 Impact factor: 9.079
Authors: P Teja-Isavadharm; G Watt; C Eamsila; K Jongsakul; Q Li; G Keeratithakul; N Sirisopana; L Luesutthiviboon; T G Brewer; D E Kyle Journal: Am J Trop Med Hyg Date: 2001-12 Impact factor: 2.345
Authors: Se Hoon Hong; Dae-Hee Lee; Young-Sun Lee; Min Jee Jo; Yoon A Jeong; William T Kwon; Haroon A Choudry; David L Bartlett; Yong J Lee Journal: Oncotarget Date: 2017-12-08
Authors: Bhavishya Sarma; Christoph Willmes; Laura Angerer; Christian Adam; Jürgen C Becker; Thibault Kervarrec; David Schrama; Roland Houben Journal: Cancers (Basel) Date: 2020-04-09 Impact factor: 6.639