Rosiglitazone counteracts palmitate-induced beta-cell dysfunction by suppression of MAP kinase, inducible nitric oxide synthase and caspase 3 activities.
Abaraviciene, S ; Lundquist, Ingmar LU and Salehi, S Albert LU
(2008)
In Cellular and Molecular Life Sciences
65(14).
p.2256-2265
- Abstract
- Chronic exposure of pancreatic islets to elevated levels of palmitate leads to beta-cell dysfunction. We examined possible involvement of mitogenactivated protein kinases (MAPKs) and caspase-3 in palmitate-induced beta-cell dysfunction and tested the influence of the anti-diabetic drug rosiglitazone (ROZ). Palmitate amplified glucose-stimulated augmentation of intracellular free calcium ([Ca(2+)](i)) and insulin secretion in incubated islets. ROZ suppressed this amplification, whereas it modestly augmented glucose-induced increase in these events. ROZ suppressed short-term palmitate-induced phosphorylation of pro-apoptotic MAPKs, i.e., SAPK/JNK and p38. Long-term islet culturing with palmitate induced inducible nitric oxide synthase (iNOS)... (More)
- Chronic exposure of pancreatic islets to elevated levels of palmitate leads to beta-cell dysfunction. We examined possible involvement of mitogenactivated protein kinases (MAPKs) and caspase-3 in palmitate-induced beta-cell dysfunction and tested the influence of the anti-diabetic drug rosiglitazone (ROZ). Palmitate amplified glucose-stimulated augmentation of intracellular free calcium ([Ca(2+)](i)) and insulin secretion in incubated islets. ROZ suppressed this amplification, whereas it modestly augmented glucose-induced increase in these events. ROZ suppressed short-term palmitate-induced phosphorylation of pro-apoptotic MAPKs, i.e., SAPK/JNK and p38. Long-term islet culturing with palmitate induced inducible nitric oxide synthase (iNOS) and activated SAPK/JNK-p38. ROZ counteracted these effects. Both palmitate and cytokines activated caspase-3 in MIN6c4-cells and isolated islets. ROZ suppressed palmitate- but not cytokine-induced caspase-3 activation. Finally, after palmitate culturing, ROZ reversed the inhibitory effect on glucose-stimulated insulin release. We suggest that ROZ counteracts palmitateinduced deleterious effects on beta-cell function via suppression of iNOS, pro-apoptotic MAPKs and caspase-3 activities, as evidenced by restoration of glucose-stimulated insulin release. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1168746
- author
- Abaraviciene, S
; Lundquist, Ingmar
LU
and Salehi, S Albert
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cellular and Molecular Life Sciences
- volume
- 65
- issue
- 14
- pages
- 2256 - 2265
- publisher
- Birkhäuser Verlag
- external identifiers
-
- wos:000257770600011
- pmid:18560759
- scopus:47749122129
- pmid:18560759
- ISSN
- 1420-9071
- DOI
- 10.1007/s00018-008-8100-8
- language
- English
- LU publication?
- yes
- id
- f8a380fd-2f64-4f05-97a8-1108e23ced05 (old id 1168746)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18560759?dopt=Abstract
- date added to LUP
- 2016-04-01 13:17:16
- date last changed
- 2022-01-27 18:24:17
@article{f8a380fd-2f64-4f05-97a8-1108e23ced05,
abstract = {{Chronic exposure of pancreatic islets to elevated levels of palmitate leads to beta-cell dysfunction. We examined possible involvement of mitogenactivated protein kinases (MAPKs) and caspase-3 in palmitate-induced beta-cell dysfunction and tested the influence of the anti-diabetic drug rosiglitazone (ROZ). Palmitate amplified glucose-stimulated augmentation of intracellular free calcium ([Ca(2+)](i)) and insulin secretion in incubated islets. ROZ suppressed this amplification, whereas it modestly augmented glucose-induced increase in these events. ROZ suppressed short-term palmitate-induced phosphorylation of pro-apoptotic MAPKs, i.e., SAPK/JNK and p38. Long-term islet culturing with palmitate induced inducible nitric oxide synthase (iNOS) and activated SAPK/JNK-p38. ROZ counteracted these effects. Both palmitate and cytokines activated caspase-3 in MIN6c4-cells and isolated islets. ROZ suppressed palmitate- but not cytokine-induced caspase-3 activation. Finally, after palmitate culturing, ROZ reversed the inhibitory effect on glucose-stimulated insulin release. We suggest that ROZ counteracts palmitateinduced deleterious effects on beta-cell function via suppression of iNOS, pro-apoptotic MAPKs and caspase-3 activities, as evidenced by restoration of glucose-stimulated insulin release.}},
author = {{Abaraviciene, S and Lundquist, Ingmar and Salehi, S Albert}},
issn = {{1420-9071}},
language = {{eng}},
number = {{14}},
pages = {{2256--2265}},
publisher = {{Birkhäuser Verlag}},
series = {{Cellular and Molecular Life Sciences}},
title = {{Rosiglitazone counteracts palmitate-induced beta-cell dysfunction by suppression of MAP kinase, inducible nitric oxide synthase and caspase 3 activities.}},
url = {{http://dx.doi.org/10.1007/s00018-008-8100-8}},
doi = {{10.1007/s00018-008-8100-8}},
volume = {{65}},
year = {{2008}},
}