Tohoku J. Exp. Med., 2009, 217(1)

Adiponectin Reduces Glucotoxicity-Induced Apoptosis of INS-1 Rat Insulin-Secreting Cells on a Microfluidic Chip

PENG LIN,¹ LI CHEN,¹ DONG LI,² JINBO LIU,¹ NAILONG YANG,³ YU SUN,¹ YUXIN XU,¹ YILING FU¹ and XINGUO HOU¹

¹Department of Endocrine, Qilu Hospital, Shandong University, Shandong, PR China
²Cryomedicine Laboratory, Qilu Hospital, Shandong University, Shandong, PR China
³Department of Endocrine, Qingdao University Medical School affiliated Hospital, Qing'dao, PR China

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/l) 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 from 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.

keywords —— Diabetes mellitus; INS-1 cell line; adiponectin; apoptosis; microfluidic microchip.

© 2009 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2009, 217, 59-65

Correspondence: Li Chen, Department of Endocrine, Qilu Hospital, Shandong University, Ji'nan 250012, Shandong, PR China.

e-mail: lp2006y@126.com