| [BACKGROUD AND OBJECTIVE]Although the development of type 2 diabetes is more complex and incompletely clear in etiology,it is usually associated with a combination of pancreaticβ-cell dysfunction and insulin resistance.Moreover,β-cell dysfunction has played a decisive role in the progress that diabetes come into being. Chronically elevated levels of glucose and lipids are known as the initiated factors and also the hallmark of diabetes.Arecoline is extracted from natural plant alkaloid. In vitro study, found that oral administration of arecoline in keratinocyte cells inhibits interleukin, and tumor necrosis factor expression, reduced ox- LDL and high glucose in vascular endothelial cells and macrophages in the expression of inflammatory factors, with anti-atherosclerosis The role of atherosclerosis;. Speculated that arecoline can protectβcells, thus improving diabetes.With regards to this, we will investigate the effect of different concentrations of arecoline on the levels of fasting blood glucose and the expression of insulin secretion factors, transcription factors, and key factors of insulin signal pathway in type 2 diabetes rats induced by high-glucose diet, and explore the underlying mechanisms. [METHODS]1) A type 2 diabetic rat model was established by fed with high fructose diet;2) The blood glucose, lipid level ,fasting plasma glucagon and fasting insulin were measured;3) Pathogenic changes of rats pancreatic tissue by Hematoxylin-eosin staining ;4) Apoptosis of rats pancreatic tissue by tunel staining ;5) The mRNA expression of pancreatic Bcl2 , Bax, PDX-1 , Insulin, GLUT2 , GK , IRS-1 , IRS-2 were detected by Reverse transcription polymerase chain reaction (RT-PCR);6) The protein expression of p-AKT and FoxO1 was detected by western blotting.[RESULTS]1. arecoline can safely decrease the level of fasting blood glucose and TG in type 2 diabetes rats.1) Type 2 diabetes rats were treated with 0.5, 1, 5, 10, 20, 50 mg/kg arecoline with abdominal injection for 4 weeks. The level of body weight, fasting blood glucose, lipid level, fasting plasma glucagon and fasting insulin were decreased, but not 0.5 mg/kg arecoline (p<0.05) .2) HE staining of pancreatic shows that 1, 5 mg/kg arecoline can improve pancreatic injury in type 2 diabetes rats induced by high-glucose diet, such as decreased the number of impairment cells. But 10, 20, 50 mg/kg arecoline have toxicants in pancreatic. 3) The apoptotic index measured by TUNEL increased gradually with adding the concentrations of 10, 20, 50 mg/kg arecoline.2. arecoline can augmentation the rate of Bcl2/Bax in type 2 diabetes rats.1) The results showed that the mRNA levels of Bcl2 reduced in type 2 diabetes rat .2) 1, 5 mg/kg arecoline can increased the mRNA levels of Bcl2 in type 2 diabetes rat paccreatic.3) Control+arecoline groups was not significantly different compared to control group.3. arecoline can increase the mRNA PDX-1,Insulin,GLUT2 and GK level of in type 2 diabetes rats.1) The results showed that the mRNA levels of PDX-1,Insulin,GLUT2 and GK were reduced in type 2 diabetes rat .2) 1, 5 mg/kg arecoline can increased the mRNA levels of PDX-1,Insulin,GLUT2 and GK in type 2 diabetes rat pancreatic.3) Control+arecoline groups was not significantly different compared to control group.4. arecoline can improve the insulin sensitivity of pancreatic in type 2 diabetes rats .1) IRS-2, IRS-2 mRNA and the p-AKT protein were down-regulated in type 2 diabetes rats liver. 2) 1, 5 mg/kg arecoline can up-regulated IRS-2,IRS-2 mRNA and the p-AKT protein in type 2 diabetes rats pancreatic.3) Control+arecoline groups was not significantly different compared to control group.[CONCLUSION]1. can be with adding the concentrations arecoline (1, 5 mg/kg) in type 2 diabetes rats2. The mechanism of improve about glucose metabolism may be through the insulin signal pathway in pancreas ,up-regulate the insulin receptor substrate, by the PI3K/AKT pathway, to influence antiapoptotic gene expression, protectβcells, or inhibit the expression of FoxO1, increases insulin secretion and glucose metabolism gene transcription, promote insulin secretion, enhance glucose metabolism... |
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