Taspoglutide, a novel human once-weekly GLP-1 analogue, protects pancreatic β-cells in vitro and preserves islet structure and function in the Zucker diabetic fatty rat in vivo
Aim: Glucagon-like peptide-1 (GLP-1) has protective effects on pancreatic β-cells. We evaluated the effects of a novel, long-acting human GLP-1 analogue, taspoglutide, on β-cells in vitro and in vivo. Methods: Proliferation of murine pancreatic β (MIN6B1) cells and rat islets in culture was assessed...
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Published in | Diabetes, obesity & metabolism Vol. 13; no. 4; pp. 326 - 336 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.04.2011
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Aim: Glucagon-like peptide-1 (GLP-1) has protective effects on pancreatic β-cells. We evaluated the effects of a novel, long-acting human GLP-1 analogue, taspoglutide, on β-cells in vitro and in vivo. Methods: Proliferation of murine pancreatic β (MIN6B1) cells and rat islets in culture was assessed by imaging of 5-ethynyl-2′-deoxyuridine-positive cells after culture with taspoglutide. Apoptosis was evaluated with the transferase-mediated 2′-deoxyuridine 5′-triphosphate nick-end labelling assay in rat insulinoma (INS-1E) cells and isolated human islets exposed to cytokines (recombinant interleukin-1β, interferon-γ, tumour necrosis factor-α) or lipotoxicity (palmitate) in the presence or absence of taspoglutide. Islet morphology and survival and glucose-stimulated insulin secretion in perfused pancreata were assessed 3-4 weeks after a single application of taspoglutide to prediabetic 6-week-old male Zucker diabetic fatty (ZDF) rats. Results: Proliferation was increased in a concentration-dependent manner up to fourfold by taspoglutide in MIN6B1 cells and was significantly stimulated in isolated rat islets. Taspoglutide almost completely prevented cytokine- or lipotoxicity-induced apoptosis in INS-1E cells (control 0.5%, cytokines alone 2.2%, taspoglutide + cytokines 0.6%, p < 0.001; palmitate alone 8.1%, taspoglutide + palmitate 0.5%, p < 0.001) and reduced apoptosis in isolated human islets. Treatment of ZDF rats with taspoglutide significantly prevented β-cell apoptosis and preserved healthy islet architecture and insulin staining intensity as shown in pancreatic islet cross sections. Basal and glucose-stimulated insulin secretion of in situ perfused ZDF rat pancreata was normalized after taspoglutide treatment. Conclusions: Taspoglutide promoted β-cell proliferation, prevented apoptosis in vitro and exerted multiple β-cell protective effects on islet architecture and function in vivo in ZDF rats. |
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Bibliography: | http://dx.doi.org/10.1111/j.1463-1326.2010.01352.x ark:/67375/WNG-N3JBWN3C-S istex:2797C87855D6249C30A3C69CF8579F2EC642148E ArticleID:DOM1352 Both these authors shared first authorship. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1462-8902 1463-1326 |
DOI: | 10.1111/j.1463-1326.2010.01352.x |