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  • Bugliani, MarcoUniversity of Pisa (author)

DPP-4 is expressed in human pancreatic beta cells and its direct inhibition improves beta cell function and survival in type 2 diabetes

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • Elsevier BV,2018

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:29f386d9-ebb9-46e6-9870-57ecf5aa8998
  • https://lup.lub.lu.se/record/29f386d9-ebb9-46e6-9870-57ecf5aa8998URI
  • https://doi.org/10.1016/j.mce.2018.01.019DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Syed, FarooqUniversity of Pisa (author)
  • Paula, Flavia M.M.Université Libre de Bruxelles (ULB) (author)
  • Omar, Bilal A.Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-bor (author)
  • Suleiman, MaraUniversity of Pisa (author)
  • Mossuto, SandraUniversity of Pisa (author)
  • Grano, FrancescaUniversity of Pisa (author)
  • Cardarelli, FrancescoScuola Normale Superiore di Pisa (author)
  • Boggi, UgoUniversity of Pisa (author)
  • Vistoli, FabioUniversity of Pisa (author)
  • Filipponi, FrancoUniversity of Pisa (author)
  • De Simone, PaoloUniversity of Pisa (author)
  • Marselli, LorellaUniversity of Pisa (author)
  • De Tata, VincenzoUniversity of Pisa (author)
  • Ahren, BoLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-bah (author)
  • Eizirik, Decio L.Université Libre de Bruxelles (ULB) (author)
  • Marchetti, PieroUniversity of Pisa (author)
  • University of PisaUniversité Libre de Bruxelles (ULB) (creator_code:org_t)

Related titles

  • In:Molecular and Cellular Endocrinology: Elsevier BV473, s. 186-1930303-7207

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