Adiponectin reduces glucotoxicity-induced apoptosis of INS-1 rat insulin-secreting cells on a microfluidic chip.
Diabetes mellitus is a metabolic disorder characterized by elevated blood sugar and progressive failure of insulin-producing beta-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 beta-cell apoptosis. Therefore, rescuing pancreatic beta-cells from glucotoxicity-induced beta-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 beta-cells, because INS-1 cells show the susceptibility to glucotoxicity, as seen in beta-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 beta-cells, at least in part, by transiently activating AMPK signaling pathway.
Lin
Peng
P
Department of Endocrine, Qilu Hospital, Shandong University, Ji'nan, Shandong, PR China. lp2006y@126.com
Chen
Li
L
Li
Dong
D
Liu
Jinbo
J
Yang
Nailong
N
Sun
Yu
Y
Xu
Yuxin
Y
Fu
Yiling
Y
Hou
Xinguo
X
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000633:toxicity; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D046210:Microfluidic Analytical Techniques; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D052242:Adiponectin; D018398:Homeodomain Proteins; D007328:Insulin; D012333:RNA, Messenger; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D055372:AMP-Activated Protein Kinases; D005947:Glucose