DPP-4 is expressed in human pancreatic beta cells and its direct inhibition improves beta cell function and survival in type 2 diabetes
| العنوان: | DPP-4 is expressed in human pancreatic beta cells and its direct inhibition improves beta cell function and survival in type 2 diabetes |
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| المؤلفون: | Francesco Cardarelli, Franco Filipponi, Mara Suleiman, Fabio Vistoli, Sandra Mossuto, Ugo Boggi, Decio L. Eizirik, Lorella Marselli, Flavia M.M. Paula, Francesca Grano, Bilal Omar, Paolo De Simone, Farooq Syed, Piero Marchetti, Vincenzo De Tata, Bo Ahrén, Marco Bugliani |
| المساهمون: | Bugliani, Marco, Syed, Farooq, Paula, Flavia M M, Omar, Bilal A, Suleiman, Mara, Mossuto, Sandra, Grano, Francesca, Cardarelli, Francesco, Boggi, Ugo, Vistoli, Fabio, Filipponi, Franco, De Simone, Paolo, Marselli, Lorella, De Tata, Vincenzo, Ahren, Bo, Eizirik, Decio L, Marchetti, Piero |
| المصدر: | Molecular and cellular endocrinology (2018). doi:10.1016/j.mce.2018.01.019 info:cnr-pdr/source/autori:Bugliani M.; Syed F.; Paula F.M.M.; Omar B.A.; Suleiman M.; Mossuto S.; Grano F.; Cardarelli F.; Boggi U.; Vistoli F.; Filipponi F.; De Simone P.; Marselli L.; De Tata V.; Ahren B.; Eizirik D.L.; Marchetti P./titolo:DPP-4 is expressed in human pancreatic beta cells and its direct inhibition improves beta cell function and survival in type 2 diabetes/doi:10.1016%2Fj.mce.2018.01.019/rivista:Molecular and cellular endocrinology (Print)/anno:2018/pagina_da:/pagina_a:/intervallo_pagine:/volume Molecular and Cellular Endocrinology |
| بيانات النشر: | North-Holland, Amsterdam , Paesi Bassi, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, endocrine system, animal structures, endocrine system diseases, Cell Survival, Dipeptidyl Peptidase 4, Down-Regulation, Alpha (ethology), Incretin, 030209 endocrinology & metabolism, Apoptosis, Biochemistry, Glucagon, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, DPP-4, Insulin-Secreting Cells, Insulin Secretion, medicine, Humans, Secretion, Beta (finance), Molecular Biology, Cytokine, Aged, Dipeptidyl-Peptidase IV Inhibitors, geography, geography.geographical_feature_category, Chemistry, Pancreatic islets, Beta cells, Apoptosi, Type 2 diabetes, Middle Aged, Islet, Molecular biology, MK-0626, 3. Good health, Beta cell, 030104 developmental biology, medicine.anatomical_structure, Diabetes Mellitus, Type 2, Cytoprotection, Cytokines, Female |
| الوصف: | It has been reported that the incretin system, including regulated GLP-1 secretion and locally expressed DPP-4, is present in pancreatic islets. In this study we comprehensively evaluated the expression and role of DPP-4 in islet alpha and beta cells from non-diabetic (ND) and type 2 diabetic (T2D) individuals, including the effects of its inhibition on beta cell function and survival. Isolated islets were prepared from 25 ND and 18 T2D organ donors; studies were also performed with the human insulin-producing EndoC-βH1 cells. Morphological (including confocal microscopy), ultrastructural (electron microscopy, EM), functional (glucose-stimulated insulin secretion), survival (EM and nuclear dyes) and molecular (RNAseq, qPCR and western blot) studies were performed under several different experimental conditions. DPP-4 co-localized with glucagon and was also expressed in human islet insulin-containing cells. Furthermore, DPP-4 was expressed in EndoC-βH1 cells. The proportions of DPP-4 positive alpha and beta cells and DPP-4 gene expression were significantly lower in T2D islets. A DPP-4 inhibitor protected ND human beta cells and EndoC-βH1 cells against cytokine-induced toxicity, which was at least in part independent from GLP1 and associated with reduced NFKB1 expression. Finally, DPP-4 inhibition augmented glucose-stimulated insulin secretion, reduced apoptosis and improved ultrastructure in T2D beta cells. These results demonstrate the presence of DPP-4 in human islet alpha and beta cells, with reduced expression in T2D islets, and show that DPP-4 inhibition has beneficial effects on human ND and T2D beta cells. This suggests that DPP-4, besides playing a role in incretin effects, directly affects beta cell function and survival. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a14d9e218c99b3ba4788b073f52a9cccTest https://publications.cnr.it/doc/386866Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a14d9e218c99b3ba4788b073f52a9ccc |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |