Jiaojiao Su1,2, Wenjing Pang3,4, Aisen Zhang5,6, Lei Li7,8, Weiyan Yao9, Xin Dai10. 1. Department of Gastroenterology, Lu'an Hospital of Anhui Medical University, Lu'an, China. 2. Department of Gastroenterology, Lu'an People's Hospital of Anhui Province, Lu'an, China. 3. Digestive Disease Research and Clinical Translation Center, Shanghai Jiaotong University, Shanghai, China. pangwj83@126.com. 4. Department of Gastroenterology, Shanghai Jiaotong University School of Medicine Affiliating Shanghai 9th People's Hospital, 639, Zhi Zao Ju Road, Shanghai, 200001, China. pangwj83@126.com. 5. Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical, Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. 6. Department of Gerontology, Jiangsu People's Hospital Affiliating to Nanjing Medical University, Nanjing, China. 7. Digestive Disease Research and Clinical Translation Center, Shanghai Jiaotong University, Shanghai, China. 8. Department of Gastroenterology, Shanghai Jiaotong University School of Medicine Affiliating Shanghai 9th People's Hospital, 639, Zhi Zao Ju Road, Shanghai, 200001, China. 9. Department of Gastroenterology, Shanghai Jiaotong University School of Medicine Affiliating Shanghai Ruijin Hospital, Shanghai, China. 10. Department of Gastroenterology, Shanghai Jiaotong University School of Medicine Affiliating Shanghai Ruijin Hospital, Shanghai, China. daixinzz730@163.com.
Abstract
BACKGROUND: New onset diabetes mellitus demonstrates a roughly correlation with pancreatic cancer (PaC), which is unique in PaC and was named as PaC-induced DM, but the inner mechanism remains unclear. Exosomes mediate intercellular communication and bearing microRNAs might be direct constituent of effect in target cells. METHODS AND RESULTS: The isolated exosomes from PaC cells were used to treat pancreatic β cells or the primary mice islets, and the glucose stimulated insulin secretions were measured. We validated the exosomal miR-19a from PaC cells to be an important mediator in the down regulation of insulin secretion by targeting Neurod1, the validated gene involved in insulin secretion, by using the quantitative real-time PCR, western blot, and promoter luciferase activity. The relative insulin, cAMP and Ca2+ expressions were also assayed to verify the inverse correlation between cancerous miR-19a and pancreatic islets Neurod1. CONCLUSIONS: Our study indicated that signal changes between cancer cells and β cells via exosomes might be important in the pathogenesis of PaC-induced DM and supplemented the pathogenesis of PaC-induced DM and provide a possible access of PaC screening strategy.
BACKGROUND: New onset diabetes mellitus demonstrates a roughly correlation with pancreatic cancer (PaC), which is unique in PaC and was named as PaC-induced DM, but the inner mechanism remains unclear. Exosomes mediate intercellular communication and bearing microRNAs might be direct constituent of effect in target cells. METHODS AND RESULTS: The isolated exosomes from PaC cells were used to treat pancreatic β cells or the primary mice islets, and the glucose stimulated insulin secretions were measured. We validated the exosomal miR-19a from PaC cells to be an important mediator in the down regulation of insulin secretion by targeting Neurod1, the validated gene involved in insulin secretion, by using the quantitative real-time PCR, western blot, and promoter luciferase activity. The relative insulin, cAMP and Ca2+ expressions were also assayed to verify the inverse correlation between cancerous miR-19a and pancreatic islets Neurod1. CONCLUSIONS: Our study indicated that signal changes between cancer cells and β cells via exosomes might be important in the pathogenesis of PaC-induced DM and supplemented the pathogenesis of PaC-induced DM and provide a possible access of PaC screening strategy.