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DPP-4 is expressed ...
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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- Bugliani, Marco (författare)
- University of Pisa
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- Syed, Farooq (författare)
- University of Pisa
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- Paula, Flavia M.M. (författare)
- Université Libre de Bruxelles (ULB)
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- Omar, Bilal A. (författare)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Suleiman, Mara (författare)
- University of Pisa
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- Mossuto, Sandra (författare)
- University of Pisa
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- Grano, Francesca (författare)
- University of Pisa
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- Cardarelli, Francesco (författare)
- Scuola Normale Superiore di Pisa
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- Boggi, Ugo (författare)
- University of Pisa
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- Vistoli, Fabio (författare)
- University of Pisa
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- Filipponi, Franco (författare)
- University of Pisa
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- De Simone, Paolo (författare)
- University of Pisa
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- Marselli, Lorella (författare)
- University of Pisa
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- De Tata, Vincenzo (författare)
- University of Pisa
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- Ahren, Bo (författare)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Eizirik, Decio L. (författare)
- Université Libre de Bruxelles (ULB)
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- Marchetti, Piero (författare)
- University of Pisa
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- Engelska.
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207. ; 473, s. 186-193
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Apoptosis
- Beta cells
- Cytokines
- DPP-4
- MK-0626
- Type 2 diabetes
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Bugliani, Marco
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Syed, Farooq
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Paula, Flavia M. ...
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Omar, Bilal A.
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Suleiman, Mara
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Mossuto, Sandra
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visa fler...
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Grano, Francesca
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Cardarelli, Fran ...
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Boggi, Ugo
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Vistoli, Fabio
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Filipponi, Franc ...
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De Simone, Paolo
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Marselli, Lorell ...
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De Tata, Vincenz ...
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Ahren, Bo
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Eizirik, Decio L ...
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Marchetti, Piero
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visa färre...
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MEDICIN OCH HÄLS ...
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och Endokrinologi oc ...
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Molecular and Ce ...
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Lunds universitet