P38 Plays an Important Role in Glucolipotoxicity-Induced Apoptosis in INS-1 Cells. (5th March 2014)

• Record Type: Journal Article
• Authors: Zhou, Lingli; Cai, Xiaoling; Han, Xueyao; Ji, Linong
• Other Names: Li Yanbing Academic Editor.
• Is Part Of: Journal of diabetes research. Volume 2014(2014)
• Publication Date: 2014-03-05
• Subjects: Diabetes -- Periodicals; Diabetes -- Pathophysiology -- Periodicals; Diabetes -- Prevention -- Periodicals; Diabetes -- Etiology -- Periodicals; Diabetes -- Epidemiology -- Periodicals; Diabetes -- Pathogenesis -- Periodicals; 616.462005
• DOI: 10.1155/2014/834528
• Languages: English
• ISSNs: 2314-6745

Abstract

Abstract : Objectives . The mechanism underlying the regulation of glucolipotoxicity-induced apoptosis by MAPKs was examined in INS-1 cells. Methods . The rat insulinoma cell line INS-1 was cotreated with glucose (30 mM) and palmitic acid (0.2 mM) (GLU+PA). Apoptosis was assessed by cell morphology and detection of PARP cleavage. The activation of MAPKs was examined by Western blotting using specific antibodies against the phosphorylated forms of JNK, ERK1/2, and P38. Results . (1) Live cell imaging studies showed that treatment with GLU+PA for 72 h induced significant cell death, concomitant with PARP-1 cleavage and caspase-3 activation, which peaked at 96 h of treatment. (2) Western blot analysis of the activation of MAPKs during GLU+PA-induced INS-1 cell apoptosis showed that phosphorylation of P38 increased gradually and reached a peak at 96 h, which coincided with PARP-1 cleavage. A transient increase of ERK activation was followed by a rapid decline at 96 h, whereas JNK phosphorylation status remained unchanged in response to GLU+PA. (3) Phosphorylation of insulin receptor substrate (IRS)-2 at 48 h of treatment triggered its degradation, which coincided with P38 activation. (4) Inhibition of P38, but not JNK or ERK, blocked GLU+PA-induced INS-1 cell apoptosis. Conclusions . P38 may be involved in the regulation of glucolipotoxicity-induced apoptosis through the phosphorylation of IRS-2.