July - September 2011, Volume 7, Issue 3

Zhao S, Zhang W, Li Y, He B, Han P

Effect of Blood Glucose Fluctuation on Apoptosis of Rat Hepatocytes in vivo

Acta Endo (Buc) 2011, 7 (3): 325-336
doi: 10.4183/aeb.2011.325

Background. Blood glucose levels in the human body continuously fluctuate within a certain range. Intermittent hyperglycemia has adverse effects on vascular endothelial\r\ncells and pancreatic beta cells. A few studies have found that blood glucose fluctuation induced apoptosis of both endothelial cells and pancreatic beta cells, possibly due to oxidative stress. This study aimed to determine the\r\neffects of blood glucose fluctuation on hepatocytes in vivo.\r\nMaterials and Methods. To induce intermittent hyperglycemia, rats were intermittently treated with 50% glucose\r\ninjection to fluctuate blood glucose between 5.5 mmol/L and 20.0 mmol/L. The rats with intermittent hyperglycemia were treated with either low dose (0.35 mg/kg?min) or high dose\r\n(0.70 mg/kg?min) N-acetylcysteine (NAC). The rats infused with saline were used as control. Apoptosis was assessed by TUNEL assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver, as well as plasma ALT, AST, TBIL, and IBIL, were examined using colorimetric kits.\r\nResults. Liver function was lower in the rats with intermittent hyperglycemia than in control rats. Hepatocytes exposed to blood glucose fluctuation were more likely\r\nto undergo apoptosis compared to control group (0.07?0.016 vs. 0.015?0.009, P<0.01). The expression of Caspase-3 and\r\ncleaved Caspase-3 was significantly higher in the IHG group than in the SAL group (0.111?0.015 vs. 0.07?0.011; 0.064?0.012 vs. 0.004?0.001, P<0.05).The expression of\r\nBax and the ratio of Bax to Bcl-2 were significantly higher in the IHG group than in the SAL group (0.20?0.05 vs. 0.10?0.02; 0.55?0.20 vs. 0.20?0.05, both P<0.01). When treated with NAC, the liver function of rats with intermittent hyperglycemia improved remarkably, and hepatocyte apoptosis decreased.\r\nConclusion. Blood glucose fluctuation appears to be detrimental to liver function, but this effect can be ameliorated by NAC.

Keywords: blood glucose fluctuation, hepatocyte, apoptosis

Correspondence: Ping Han, Department of Endocrinology, Shengjing Hospital, China Medical University, Shenyang 110004 China, Email:shuangxicmu@163.com, Tel: +86-24-15940502858,\r\nFax: +86-24-22834060