Objective:To investigate the effect of Dan-gua Fang(丹瓜方) on adenosine 5’-monophosphate(AMP) activated protein kinase(AMPK) α expression in liver and subsequent improvement of glucose and lipid metabolism.M...Objective:To investigate the effect of Dan-gua Fang(丹瓜方) on adenosine 5’-monophosphate(AMP) activated protein kinase(AMPK) α expression in liver and subsequent improvement of glucose and lipid metabolism.Methods:Forty 13-week-old diabetic Goto-Kakizaki(GK) rats were randomly divided into model,Dan-gua Fang,metformin and simvastatin groups(n=10 for each),and fed high-fat diet ad libitum.Ten Wistar rats were used as normal group and fed normal diet.After 24 weeks,liver expression of AMPK α mRNA was assessed by real-time PCR.AMPK α and phospho-AMPK α protein expression in liver was evaluated by Western blot.Liver histomorphology was carried out after hematoxylin-eosin staining,and blood glucose(BG),glycosylated hemoglobin A1c(HbA1c),food intake and body weight recorded.Results:Similar AMPK α mRNA levels were found in the Dan-gua Fang group and normal group,slightly higher than the values obtained for the remaining groups(P〈0.05).AMPK α protein expression in the Dan-gua Fang group animals was similar to other diabetic rats,whereas phospho-AMPK α(Thr-172) protein levels were markedly higher than in the metformin group and simvastatin group(P〈0.05),respectively.However,phosphor-AMPKa/AMPK α ratios were similar in all groups.Dan-gua Fang reduced fasting blood glucose with similar strength to metformin,and was superior in reducing cholesterol,triglycerides,high-density lipoprotein cholesterol as well as improving low-density lipoprotein cholesterol in comparison with simvastatin and metformin.Dan-gua Fang decreases plasma alanine aminotransferase(ALT) significantly.Conclusion:Dan-gua Fang,while treating phlegm-stasis,could decrease BG and lipid in type 2 diabetic GK rats fed with high-fat diet,and effectively protect liver histomorphology and function.This may be partly explained by increased AMPK expression in liver.Therefore,Dan-gua Fang might be an ideal drug for comprehensive Intervention for glucose and lipid metabolism disorders in type 2 diabetes mellitus.展开更多
The Goto-Kakizaki(GK) rat is a spontaneous type 2 diabetic animal model,which is characterized by a progressive loss of beta islet cells with fibrosis.In the present study,the hypoglycemic effect of asiatic acid(AA) i...The Goto-Kakizaki(GK) rat is a spontaneous type 2 diabetic animal model,which is characterized by a progressive loss of beta islet cells with fibrosis.In the present study,the hypoglycemic effect of asiatic acid(AA) in GK rats was examined.GK rats receiving AA at a daily dose of 25 mg·kg-1 for four weeks showed a significant reduction in blood glucose levels.Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose(CMC-Na) solution for the same periods and used as control.Compared to the normal Wistar rats,GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level(P < 0.01) and insulin level(P < 0.05).Furthermore,the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats.Fibronectin,a key protein related to islet fibrosis,was over-expressed in GK rats,which was reversed significantly by AA treatment(P < 0.05).These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes,which may play a role in the prevention of islets展开更多
目的:探讨GK大鼠行胃转流术后空腹血糖及骨骼肌SIRT3酶的变化及意义;方法:24只Goto-Kakizaki(GK)大鼠随机分为手术组(operation group OG组,假手术组(sim-operation group SG组)和对照组(control group CG组);OG组大鼠行胃转流手术,SG...目的:探讨GK大鼠行胃转流术后空腹血糖及骨骼肌SIRT3酶的变化及意义;方法:24只Goto-Kakizaki(GK)大鼠随机分为手术组(operation group OG组,假手术组(sim-operation group SG组)和对照组(control group CG组);OG组大鼠行胃转流手术,SG组大鼠行假手术,CG组仅作术前对照,OG组和SG组分别测定术前、术后48h和1、2及4周空腹血糖水平,术后4周处死取大腿部骨骼肌用western blot法半定量测定其SIRT3酶值;CG组监测空腹血糖水平,4周后处死同法测定大腿骨骼肌SIRT3酶值。结果:术前3组大鼠空腹血糖水平相仿,术后OG组血糖水平进行性下降,2周后血糖水平稳定,与SG组和CG组比较明显降低(P﹤0.05),SG组与CG组各时相空腹血糖水平差异无统计学意义(P﹥0.05);OG组术后骨骼肌SIRT3酶表达与明显增加,与SG组和CG组比较差异有统计学意义;结论:胃转流术可降低GK大鼠空腹血糖,骨骼肌SIRT3酶表达的增加可能是其糖尿病改善的机制之一。展开更多
基金Supported by the National Natural Science Foundation of China(No.81173179)the Natural Science Foundation of Fujian Province(No.2011J01198)+5 种基金the Fujian Medical Innovation Project(No.2009-CX-19)the Research Foundation of Fujian Health Department(No.Zlcnfm02)the Fujian Provincial Department of Education Category A Projects(No.JA09131)the Fujian Health Department of Traditional Chinese Medicine Research(No.WZY0920)the CHEN Ke-ji Integrative Medicine Development Fund(No.CKJ2008047,CKJ2009004)the Integrative Medicine of Fujian Key Laboratory of Age-related Diseases Funded Projects(No.2008J1004-10)
文摘Objective:To investigate the effect of Dan-gua Fang(丹瓜方) on adenosine 5’-monophosphate(AMP) activated protein kinase(AMPK) α expression in liver and subsequent improvement of glucose and lipid metabolism.Methods:Forty 13-week-old diabetic Goto-Kakizaki(GK) rats were randomly divided into model,Dan-gua Fang,metformin and simvastatin groups(n=10 for each),and fed high-fat diet ad libitum.Ten Wistar rats were used as normal group and fed normal diet.After 24 weeks,liver expression of AMPK α mRNA was assessed by real-time PCR.AMPK α and phospho-AMPK α protein expression in liver was evaluated by Western blot.Liver histomorphology was carried out after hematoxylin-eosin staining,and blood glucose(BG),glycosylated hemoglobin A1c(HbA1c),food intake and body weight recorded.Results:Similar AMPK α mRNA levels were found in the Dan-gua Fang group and normal group,slightly higher than the values obtained for the remaining groups(P〈0.05).AMPK α protein expression in the Dan-gua Fang group animals was similar to other diabetic rats,whereas phospho-AMPK α(Thr-172) protein levels were markedly higher than in the metformin group and simvastatin group(P〈0.05),respectively.However,phosphor-AMPKa/AMPK α ratios were similar in all groups.Dan-gua Fang reduced fasting blood glucose with similar strength to metformin,and was superior in reducing cholesterol,triglycerides,high-density lipoprotein cholesterol as well as improving low-density lipoprotein cholesterol in comparison with simvastatin and metformin.Dan-gua Fang decreases plasma alanine aminotransferase(ALT) significantly.Conclusion:Dan-gua Fang,while treating phlegm-stasis,could decrease BG and lipid in type 2 diabetic GK rats fed with high-fat diet,and effectively protect liver histomorphology and function.This may be partly explained by increased AMPK expression in liver.Therefore,Dan-gua Fang might be an ideal drug for comprehensive Intervention for glucose and lipid metabolism disorders in type 2 diabetes mellitus.
基金supported by the Fundamental Research Funds for the Central Universities(No.JKP2011004)
文摘The Goto-Kakizaki(GK) rat is a spontaneous type 2 diabetic animal model,which is characterized by a progressive loss of beta islet cells with fibrosis.In the present study,the hypoglycemic effect of asiatic acid(AA) in GK rats was examined.GK rats receiving AA at a daily dose of 25 mg·kg-1 for four weeks showed a significant reduction in blood glucose levels.Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose(CMC-Na) solution for the same periods and used as control.Compared to the normal Wistar rats,GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level(P < 0.01) and insulin level(P < 0.05).Furthermore,the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats.Fibronectin,a key protein related to islet fibrosis,was over-expressed in GK rats,which was reversed significantly by AA treatment(P < 0.05).These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes,which may play a role in the prevention of islets
文摘目的:探讨GK大鼠行胃转流术后空腹血糖及骨骼肌SIRT3酶的变化及意义;方法:24只Goto-Kakizaki(GK)大鼠随机分为手术组(operation group OG组,假手术组(sim-operation group SG组)和对照组(control group CG组);OG组大鼠行胃转流手术,SG组大鼠行假手术,CG组仅作术前对照,OG组和SG组分别测定术前、术后48h和1、2及4周空腹血糖水平,术后4周处死取大腿部骨骼肌用western blot法半定量测定其SIRT3酶值;CG组监测空腹血糖水平,4周后处死同法测定大腿骨骼肌SIRT3酶值。结果:术前3组大鼠空腹血糖水平相仿,术后OG组血糖水平进行性下降,2周后血糖水平稳定,与SG组和CG组比较明显降低(P﹤0.05),SG组与CG组各时相空腹血糖水平差异无统计学意义(P﹥0.05);OG组术后骨骼肌SIRT3酶表达与明显增加,与SG组和CG组比较差异有统计学意义;结论:胃转流术可降低GK大鼠空腹血糖,骨骼肌SIRT3酶表达的增加可能是其糖尿病改善的机制之一。