The adipocytokine Nampt and its product NMN have no effect on beta-cell survival but potentiate glucose stimulated insulin secretion.
AIMS/HYPOTHESIS:Obesity is associated with a dysregulation of beta-cell and adipocyte function. The molecular interactions between adipose tissue and beta-cells are not yet fully elucidated. We investigated, whether or not the adipocytokine Nicotinamide phosphoribosyltransferase (Nampt) and its enzy...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3546920?pdf=render |
| _version_ | 1819029023858098176 |
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| author | Robert Spinnler Theresa Gorski Katharina Stolz Susanne Schuster Antje Garten Annette G Beck-Sickinger Marten A Engelse Eelco J P de Koning Antje Körner Wieland Kiess Kathrin Maedler |
| author_facet | Robert Spinnler Theresa Gorski Katharina Stolz Susanne Schuster Antje Garten Annette G Beck-Sickinger Marten A Engelse Eelco J P de Koning Antje Körner Wieland Kiess Kathrin Maedler |
| author_sort | Robert Spinnler |
| collection | DOAJ |
| description | AIMS/HYPOTHESIS:Obesity is associated with a dysregulation of beta-cell and adipocyte function. The molecular interactions between adipose tissue and beta-cells are not yet fully elucidated. We investigated, whether or not the adipocytokine Nicotinamide phosphoribosyltransferase (Nampt) and its enzymatic product Nicotinamide mononucleotide (NMN), which has been associated with obesity and type 2 diabetes mellitus (T2DM) directly influence beta-cell survival and function. METHODS:The effect of Nampt and NMN on viability of INS-1E cells was assessed by WST-1 assay. Apoptosis was measured by Annexin V/PI and TUNEL assay. Activation of apoptosis signaling pathways was evaluated. Adenylate kinase release was determined to assess cytotoxicity. Chronic and acute effects of the adipocytokine Nampt and its enzymatic product NMN on insulin secretion were assessed by glucose stimulated insulin secretion in human islets. RESULTS:While stimulation of beta-cells with the cytokines IL-1β, TNFα and IFN-γ or palmitate significantly decreased viability, Nampt and NMN showed no direct effect on viability in INS-1E cells or in human islets, neither alone nor in the presence of pro-diabetic conditions (elevated glucose concentrations and palmitate or cytokines). At chronic conditions over 3 days of culture, Nampt and its product NMN had no effects on insulin secretion. In contrast, both Nampt and NMN potentiated glucose stimulated insulin secretion acutely during 1 h incubation of human islets. CONCLUSION/INTERPRETATION:Nampt and NMN neither influenced beta-cell viability nor apoptosis but acutely potentiated glucose stimulated insulin secretion. |
| first_indexed | 2024-12-21T06:07:40Z |
| format | Article |
| id | doaj.art-16ecf63bb88d40f49fadc4034a13247d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T06:07:40Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-16ecf63bb88d40f49fadc4034a13247d2022-12-21T19:13:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5410610.1371/journal.pone.0054106The adipocytokine Nampt and its product NMN have no effect on beta-cell survival but potentiate glucose stimulated insulin secretion.Robert SpinnlerTheresa GorskiKatharina StolzSusanne SchusterAntje GartenAnnette G Beck-SickingerMarten A EngelseEelco J P de KoningAntje KörnerWieland KiessKathrin MaedlerAIMS/HYPOTHESIS:Obesity is associated with a dysregulation of beta-cell and adipocyte function. The molecular interactions between adipose tissue and beta-cells are not yet fully elucidated. We investigated, whether or not the adipocytokine Nicotinamide phosphoribosyltransferase (Nampt) and its enzymatic product Nicotinamide mononucleotide (NMN), which has been associated with obesity and type 2 diabetes mellitus (T2DM) directly influence beta-cell survival and function. METHODS:The effect of Nampt and NMN on viability of INS-1E cells was assessed by WST-1 assay. Apoptosis was measured by Annexin V/PI and TUNEL assay. Activation of apoptosis signaling pathways was evaluated. Adenylate kinase release was determined to assess cytotoxicity. Chronic and acute effects of the adipocytokine Nampt and its enzymatic product NMN on insulin secretion were assessed by glucose stimulated insulin secretion in human islets. RESULTS:While stimulation of beta-cells with the cytokines IL-1β, TNFα and IFN-γ or palmitate significantly decreased viability, Nampt and NMN showed no direct effect on viability in INS-1E cells or in human islets, neither alone nor in the presence of pro-diabetic conditions (elevated glucose concentrations and palmitate or cytokines). At chronic conditions over 3 days of culture, Nampt and its product NMN had no effects on insulin secretion. In contrast, both Nampt and NMN potentiated glucose stimulated insulin secretion acutely during 1 h incubation of human islets. CONCLUSION/INTERPRETATION:Nampt and NMN neither influenced beta-cell viability nor apoptosis but acutely potentiated glucose stimulated insulin secretion.http://europepmc.org/articles/PMC3546920?pdf=render |
| spellingShingle | Robert Spinnler Theresa Gorski Katharina Stolz Susanne Schuster Antje Garten Annette G Beck-Sickinger Marten A Engelse Eelco J P de Koning Antje Körner Wieland Kiess Kathrin Maedler The adipocytokine Nampt and its product NMN have no effect on beta-cell survival but potentiate glucose stimulated insulin secretion. PLoS ONE |
| title | The adipocytokine Nampt and its product NMN have no effect on beta-cell survival but potentiate glucose stimulated insulin secretion. |
| title_full | The adipocytokine Nampt and its product NMN have no effect on beta-cell survival but potentiate glucose stimulated insulin secretion. |
| title_fullStr | The adipocytokine Nampt and its product NMN have no effect on beta-cell survival but potentiate glucose stimulated insulin secretion. |
| title_full_unstemmed | The adipocytokine Nampt and its product NMN have no effect on beta-cell survival but potentiate glucose stimulated insulin secretion. |
| title_short | The adipocytokine Nampt and its product NMN have no effect on beta-cell survival but potentiate glucose stimulated insulin secretion. |
| title_sort | adipocytokine nampt and its product nmn have no effect on beta cell survival but potentiate glucose stimulated insulin secretion |
| url | http://europepmc.org/articles/PMC3546920?pdf=render |
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