Adiponectin reduces glucotoxicity-induced apoptosis of INS-1 rat insulin-secreting cells on a microfluidic chip

Abstract

Diabetes mellitus is a metabolic disorder characterized by elevated blood sugar and progressive failure of insulin-producing β-cells. Persistent hyperglycemia and blood sugar fluctuation are two general phenomena in diabetic patients, and both of them can result in an increased frequency of β-cell apoptosis, Therefore, rescuing pancreatic β-cells from glucotoxicity-induced β-cell apoptosis is increasing viewed as a promising means for curing. The aim of this study was to investigate whether adiponectin, an important cytokine expressed in adipose tissue, has a potential for the application as the antiapoptotic strategy. INS-1 rat insulin-secreting cell line was used in this study as a model of pancreatic β-cells, because INS-1 cells show the susceptibility to glucotoxicity, as seen in β-cells. INS-1 cells were cultured on a novel microfluidic chip with persistent perfusion and subsequently exposed to sustained high glucose (SHG) (25 mmol/1) or intermittent high glucose (IHG) (11.1 and 25 mmol/l glucose alternating every 12 h) in the absence or presence of adiponectin for 72 h. Using this device, we showed that IHG induced more serious impairment in INS-1 cells than did SHG, and adiponectin partially rescued INS-1 cells froln glucotoxicity-induced apoptosis, dysfunction and reduction of insulin gene expression. Simultaneously the mRNA expression of AMP-activated protein kinase (AMPK), which is a signaling protein that acts to modulate glucose uptake in skeletal muscle, was restored in the presence of adiponectin. Based on the above evidence, we suggest that adiponectin could reduce glucotoxicity-induced apoptosis of β-cells, at least in part, by transiently activating AMPK signaling pathway. © 2009 Tohoku University Medical Press.