Rosiglitazone counteracts palmitate-induced beta-cell dysfunction by suppression of MAP kinase, inducible nitric oxide synthase and caspase 3 activities.

Summary, in English

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: S Abaraviciene; Ingmar Lundquist; S Albert Salehi
• Department/s: Islet cell physiology
• Publishing year: 2008
• Language: English
• Pages: 2256-2265
• Publication/Series: Cellular and Molecular Life Sciences
• Volume: 65
• Issue: 14
• Links: http://www.ncbi.nlm.nih.gov/pubmed/18560759?dopt=Abstract; http://dx.doi.org/10.1007/s00018-008-8100-8
• Document type: Journal article
• Publisher: Birkhäuser Verlag
• Topic: Cell Biology
• Status: Published
• Research group: Islet cell physiology
• ISBN/ISSN/Other: ISSN: 1420-9071