Effect of palmitate on TXNIP expression in INS-1 islet cells / 中国病理生理杂志

ABSTRACT

AIM:Chronic exposure to elevated levels of free fatty acids (FFAs) in type 2 diabetes patients is toxic to pancreatic β-cells.Thioredoxin (Trx)-interacting protein (TXNIP), an endogenous Trx-inhibiting protein, is up-regulated by glucose and is a critical mediator of hyperglycemia-induced β-cell apoptosis in diabetes.However, the effects of FFAs on TXNIP are unknown.In this experiment we observed the effect of palmitate on TXNIP expression in cultured INS-1 islet cells and the pathways involved were analyzed meanwhile.METHODS:After the full basis of preliminary experiment of incubating INS-1 cells with palmitate at different concentrations for different time, INS-1 islet cells were cultured with 0.5 mmol/L palmitate for 24 h.TXNIP expression, cell apoptosis, and expression of transcription factors related to TXNIP transcriptional regulation were determined.RESULTS:Compared with control group, the expression of TXNIP at mRNA and protein levels in palmitate group was significantly up-regulated (P<0.01).Cleaved caspase-3/caspase-3 ratio was increased in palmitate group (P<0.05), and the apoptosis of the INS-1 cells was also significantly increased (P<0.01).Palmitate enhanced the phosphorylation of nuclear factor-κB (NF-κB) (P<0.01), and the NF-κB inhibitors, PDTC and SN50, both blocked the palmitate-induced up-regulation of TXNIP expression.CONCLUSION:Saturated fatty acid palmitate enhances the expression of TXNIP.The mechanism of palmitate-induced TXNIP expression may be associa-ted with the increase in NF-κB phosphorylation.