Beta-cell selective KATP-channel activation protects beta-cells and human islets from human islet amyloid polypeptide induced toxicity
Background and aims - In type 2 diabetes mellitus (T2DM) chronic beta-cell stimulation and oligomers of aggregating human islet amyloid polypeptide (h-IAPP) cause beta-cell dysfunction and induce beta-cell apoptosis. Therefore we asked whether beta-cell rest prevents h-IAPP induced beta-cell apoptos...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
6 July 2010
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| In: |
Regulatory peptides
Year: 2010, Volume: 165, Issue: 2/3, Pages: 158-162 |
| ISSN: | 1873-1686 |
| DOI: | 10.1016/j.regpep.2010.06.009 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.regpep.2010.06.009 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0167011510001539 
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| Author Notes: | Robert A. Ritzel, Sajith Jayasinghe, John B. Hansen, Jeppe Sturis, Ralf Langen, Peter C. Butler |
| Summary: | Background and aims - In type 2 diabetes mellitus (T2DM) chronic beta-cell stimulation and oligomers of aggregating human islet amyloid polypeptide (h-IAPP) cause beta-cell dysfunction and induce beta-cell apoptosis. Therefore we asked whether beta-cell rest prevents h-IAPP induced beta-cell apoptosis. - Materials and methods - We induced beta-cell rest with a beta-cell selective KATP-channel opener (KATPCO) in RIN cells and human islets exposed to h-IAPP versus r-IAPP. Apoptosis was quantified by time-lapse video microscopy (TLVM) in RIN cells and TUNEL staining in human islets. Whole islets were also studied with TLVM over 48h to examine islet architecture. - Results - In RIN cells and human islets h-IAPP induced apoptosis (p<0.001 h-IAPP versus r-IAPP). Concomitant incubation with KATPCO inhibited apoptosis (p<0.001). KATPCO also reduced h-IAPP induced expansion of whole islets (disintegration of islet architecture) by ~70% (p<0.05). Thioflavin-binding assays show that KATPCO does not directly inhibit amyloid formation. - Conclusions - Opening of KATP-channels reduces beta-cell vulnerability to apoptosis induced by h-IAPP oligomers. This effect is not due to a direct interaction of KATPCO with h-IAPP, but might be mediated through hyperpolarization of the beta-cell membrane induced by opening of KATP-channels. Induction of beta-cell rest with beta-cell selective KATP-channel openers may provide a strategy to protect beta-cells from h-IAPP induced apoptosis and to prevent beta-cell deficiency in T2DM. |
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| Item Description: | Im Titel ist "ATP" nach "K" tiefgestellt Gesehen am 25.05.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1873-1686 |
| DOI: | 10.1016/j.regpep.2010.06.009 |