目的研究阿卡波糖治疗2型糖尿病(T2DM)及对血清炎性因子、抑胃肽(GIP)、胰升血糖素样肽-1(GLP-1)、空腹C肽(C-P)的影响。方法选择郑州市第一人民医院2014年7月至2018年6月收治的T2DM病人238例,按照随机数字表法分为阿卡波糖组与对照组,...目的研究阿卡波糖治疗2型糖尿病(T2DM)及对血清炎性因子、抑胃肽(GIP)、胰升血糖素样肽-1(GLP-1)、空腹C肽(C-P)的影响。方法选择郑州市第一人民医院2014年7月至2018年6月收治的T2DM病人238例,按照随机数字表法分为阿卡波糖组与对照组,各119例。对照组给予甘精胰岛素治疗,阿卡波糖组在对照组基础上给予阿卡波糖治疗。观察两组血清空腹血糖(FPG)、餐后2 h血糖(2 h PG)及糖化血红蛋白(HbA1c)等指标治疗前后的差异,观察GIP、GLP-1、C-P、白介素-4(IL-4)、白介素-6(IL-6)、白介素-10(IL-10)等治疗前后水平的变化及两组间的不良反应。结果治疗后,阿卡波糖组FPG(5.07±0.52)mmol/L、2 h PG(7.58±0.77)mmol/L、HbA1c(6.07±0.62)%、GIP(1203.58±123.83)μg/L、IL-6(2.08±0.22)ng/L水平低于对照组(6.22±0.63)mmol/L、(9.71±0.99)mmol/L、(7.18±0.73)%、(1394.38±142.55)μg/L、(2.67±0.28)ng/L水平,IL-4(4.60±0.48)ng/L、IL-10(1.43±0.16)ng/L、GLP-1(26.85±2.67)pmol/L、C-P(2.48±0.26)μg/L水平均高于对照组(4.14±0.44)ng/L、(1.18±0.13)ng/L、(23.64±2.46)pmol/L、(2.21±0.24)μg/L(P<0.05)。阿卡波糖组不良反应发生率(10.92%)与对照组(5.04%)差异无统计学意义(P>0.05)。结论阿卡波糖可有效降低T2DM病人血糖水平,抑制炎症反应,改善GIP、GLP-1、C-P水平,安全可靠。展开更多
AIM: To investigate whether a glucagon-like peptide-1(GLP-1) analogue inhibits nonalcoholic steatohepatitis(NASH), which is being increasingly recognized in Asia, in non-obese mice. METHODS: A methionine-choline-defic...AIM: To investigate whether a glucagon-like peptide-1(GLP-1) analogue inhibits nonalcoholic steatohepatitis(NASH), which is being increasingly recognized in Asia, in non-obese mice. METHODS: A methionine-choline-deficient diet(MCD) along with exendin-4(20 μg/kg per day, ip), a GLP-1 analogue, or saline was administered to male db/db mice(non-obese NASH model). Four or eight weeks after commencement of the diet, the mice were sacrificed and their livers were excised. The excised livers were examined by histochemistry for evidence of hepatic steatosis and inflammation. Hepatic triglyceride(TG) and free fatty acid(FFA) content was measured, and the expression of hepatic fat metabolism- and inflammation-related genes was evaluated. Oxidative stress-related parameters and macrophage recruitment were also examined using immunohistochemistry.RESULTS: Four weeks of MCD feeding induced hepatic steatosis and inflammation and increased the hepatic TG and FFA content. The expression of fattyacid transport protein 4(FATP4), a hepatic FFA influxrelated gene; macrophage recruitment; and the level of malondialdehyde(MDA), an oxidative stress marker, were significantly augmented by a 4-wk MCD. The levels of hepatic sterol regulatory element-binding protein-1c(SREBP-1c) m RNA(lipogenesis-related gene) and acyl-coenzyme A oxidase 1(ACOX1) m RNA(β-oxidation-related gene) had decreased at 4 wk and further decreased at 8 wk. However, the level of microsomal triglyceride transfer protein m RNA(a lipid excretion-related gene) remained unchanged. The administration of exendin-4 significantly attenuated the MCD-induced increase in hepatic steatosis, hepatic TG and FFA content, and FATP4 expression as well as the MCD-induced augmentation of hepatic inflammation, macrophage recruitment, and MDA levels. Additionally, it further decreased the hepatic SREBP-1c level and alleviated the MCD-mediated inhibition of the ACOX1 m RNA level. CONCLUSION: These results suggest that GLP-1 inhibits hepatic steatosis and inflammation through the inhibiti展开更多
目的观察白虎加人参汤对2型糖尿病(type 2 diabetes mellitus,T2DM)MKR小鼠肠道解偶联蛋白2(uncoupling protein 2,UCP2)、AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)表达及胰高血糖素样肽-1(glucagon like peptide-1,GLP-1)...目的观察白虎加人参汤对2型糖尿病(type 2 diabetes mellitus,T2DM)MKR小鼠肠道解偶联蛋白2(uncoupling protein 2,UCP2)、AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)表达及胰高血糖素样肽-1(glucagon like peptide-1,GLP-1)分泌的影响,探讨其降糖机制。方法将MKR小鼠随机分为模型组和白虎加人参汤低、高剂量组,以FVB小鼠为空白组,中药干预4周后,观察小鼠糖代谢变化;ELISA法检测小鼠血清中胰岛素(insulin,INS)、GLP-1水平;RT-qPCR检测小鼠结肠AMPK、UCP2 mRNA水平;Western blot法检测小鼠结肠P-AMPKα、UCP2蛋白表达水平;组织形态学观察小鼠结肠组织病理形态及黏液量的变化。结果白虎加人参汤低、高剂量组与模型组比较,均能显著降低MKR小鼠的空腹血糖和INS水平(P<0.01);并能提高血清GLP-1浓度(P<0.01,P<0.05);上调小鼠结肠AMPK mRNA和P-AMPKα水平(P<0.01),下调UCP2 mRNA和蛋白水平(P<0.01)。白虎加人参汤低、高剂量组均能明显改善MKR小鼠结肠组织病理形态。结论白虎加人参汤可能通过抑制UCP2表达、激活AMPK的表达,促进肠道GLP-1的分泌,发挥治疗T2DM的作用。展开更多
目的:系统评价长效胰高血糖素样肽-1(GLP-1)受体激动药索马鲁肽对比安慰剂或其他降糖药治疗2型糖尿病的疗效和安全性,为临床治疗提供循证参考。方法:计算机检索PubMed、Embase、Medline、Cochrane图书馆,检索时限为自建库起至2018年9月...目的:系统评价长效胰高血糖素样肽-1(GLP-1)受体激动药索马鲁肽对比安慰剂或其他降糖药治疗2型糖尿病的疗效和安全性,为临床治疗提供循证参考。方法:计算机检索PubMed、Embase、Medline、Cochrane图书馆,检索时限为自建库起至2018年9月,收集索马鲁肽(试验组)对比安慰剂或其他降糖药(对照组)治疗2型糖尿病疗效和安全性的随机对照试验(RCT),对符合纳入标准的临床研究进行资料提取并采用Cochrane系统评价手册5.1.0进行质量评价后,使用Rev Man 5.3软件对治疗前后患者的糖化血红蛋白(HbA_1c)水平及达标率、空腹血糖(FPG)水平、收缩压、舒张压、体质量指数(BMI)、体质量、脉搏频率水平、低血糖和胃肠道反应发生率等指标进行Meta分析。结果:共纳入12项RCT,合计9 966例患者。Meta分析结果显示,试验组相比于对照组能更有效降低HbA_1c水平[MD=-1.03,95%CI(-1.22,-0.85),P<0.001]和FPG水平[MD=-1.14,95%CI(-1.53,-0.76),P<0.001],增加受试患者HbA_1c达标率[RD=0.40,95%CI(0.31,0.49),P<0.001],同时还可降低收缩压[MD=-2.61,95%CI(-3.23,-1.98),P<0.001]、舒张压[MD=-0.56,95%CI(-0.96,-0.16),P=0.006]、BMI[MD=-1.25,95%CI(-1.51,-0.99),P<0.001],减轻体质量[MD=-3.60,95%CI(-4.24,-2.96),P<0.001],增加脉搏频率[MD=2.16,95%CI(1.51,2.81),P<0.001],差异均有统计学意义;索马鲁肽的主要不良反应为胃肠道反应,其发生率高于对照组[RD=0.20,95%CI(0.15,0.26),P<0.001]、低血糖事件的发生率与对照组比较,差异则无统计学意义[RD=0.00,95%CI(-0.01,0.02),P=0.44]。结论:索马鲁肽可明显降低2型糖尿病患者的HbA_1c、FPG、体质量、血压水平,增加脉搏频率,提高服用患者的HbA_1c达标率;同时,虽然其致胃肠道反应发生率高于对照组,但不会增加低血糖发生的风险,提示该药具有较好的耐受性和安全性。展开更多
文摘目的研究阿卡波糖治疗2型糖尿病(T2DM)及对血清炎性因子、抑胃肽(GIP)、胰升血糖素样肽-1(GLP-1)、空腹C肽(C-P)的影响。方法选择郑州市第一人民医院2014年7月至2018年6月收治的T2DM病人238例,按照随机数字表法分为阿卡波糖组与对照组,各119例。对照组给予甘精胰岛素治疗,阿卡波糖组在对照组基础上给予阿卡波糖治疗。观察两组血清空腹血糖(FPG)、餐后2 h血糖(2 h PG)及糖化血红蛋白(HbA1c)等指标治疗前后的差异,观察GIP、GLP-1、C-P、白介素-4(IL-4)、白介素-6(IL-6)、白介素-10(IL-10)等治疗前后水平的变化及两组间的不良反应。结果治疗后,阿卡波糖组FPG(5.07±0.52)mmol/L、2 h PG(7.58±0.77)mmol/L、HbA1c(6.07±0.62)%、GIP(1203.58±123.83)μg/L、IL-6(2.08±0.22)ng/L水平低于对照组(6.22±0.63)mmol/L、(9.71±0.99)mmol/L、(7.18±0.73)%、(1394.38±142.55)μg/L、(2.67±0.28)ng/L水平,IL-4(4.60±0.48)ng/L、IL-10(1.43±0.16)ng/L、GLP-1(26.85±2.67)pmol/L、C-P(2.48±0.26)μg/L水平均高于对照组(4.14±0.44)ng/L、(1.18±0.13)ng/L、(23.64±2.46)pmol/L、(2.21±0.24)μg/L(P<0.05)。阿卡波糖组不良反应发生率(10.92%)与对照组(5.04%)差异无统计学意义(P>0.05)。结论阿卡波糖可有效降低T2DM病人血糖水平,抑制炎症反应,改善GIP、GLP-1、C-P水平,安全可靠。
基金Supported by Grant-in-Aid from the Ministry of Education, Culture, Sport, Science and Technology of Japan to Nakade Y and Yoneda M and a grant from the Aikeikai Foundation
文摘AIM: To investigate whether a glucagon-like peptide-1(GLP-1) analogue inhibits nonalcoholic steatohepatitis(NASH), which is being increasingly recognized in Asia, in non-obese mice. METHODS: A methionine-choline-deficient diet(MCD) along with exendin-4(20 μg/kg per day, ip), a GLP-1 analogue, or saline was administered to male db/db mice(non-obese NASH model). Four or eight weeks after commencement of the diet, the mice were sacrificed and their livers were excised. The excised livers were examined by histochemistry for evidence of hepatic steatosis and inflammation. Hepatic triglyceride(TG) and free fatty acid(FFA) content was measured, and the expression of hepatic fat metabolism- and inflammation-related genes was evaluated. Oxidative stress-related parameters and macrophage recruitment were also examined using immunohistochemistry.RESULTS: Four weeks of MCD feeding induced hepatic steatosis and inflammation and increased the hepatic TG and FFA content. The expression of fattyacid transport protein 4(FATP4), a hepatic FFA influxrelated gene; macrophage recruitment; and the level of malondialdehyde(MDA), an oxidative stress marker, were significantly augmented by a 4-wk MCD. The levels of hepatic sterol regulatory element-binding protein-1c(SREBP-1c) m RNA(lipogenesis-related gene) and acyl-coenzyme A oxidase 1(ACOX1) m RNA(β-oxidation-related gene) had decreased at 4 wk and further decreased at 8 wk. However, the level of microsomal triglyceride transfer protein m RNA(a lipid excretion-related gene) remained unchanged. The administration of exendin-4 significantly attenuated the MCD-induced increase in hepatic steatosis, hepatic TG and FFA content, and FATP4 expression as well as the MCD-induced augmentation of hepatic inflammation, macrophage recruitment, and MDA levels. Additionally, it further decreased the hepatic SREBP-1c level and alleviated the MCD-mediated inhibition of the ACOX1 m RNA level. CONCLUSION: These results suggest that GLP-1 inhibits hepatic steatosis and inflammation through the inhibiti
文摘目的观察白虎加人参汤对2型糖尿病(type 2 diabetes mellitus,T2DM)MKR小鼠肠道解偶联蛋白2(uncoupling protein 2,UCP2)、AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)表达及胰高血糖素样肽-1(glucagon like peptide-1,GLP-1)分泌的影响,探讨其降糖机制。方法将MKR小鼠随机分为模型组和白虎加人参汤低、高剂量组,以FVB小鼠为空白组,中药干预4周后,观察小鼠糖代谢变化;ELISA法检测小鼠血清中胰岛素(insulin,INS)、GLP-1水平;RT-qPCR检测小鼠结肠AMPK、UCP2 mRNA水平;Western blot法检测小鼠结肠P-AMPKα、UCP2蛋白表达水平;组织形态学观察小鼠结肠组织病理形态及黏液量的变化。结果白虎加人参汤低、高剂量组与模型组比较,均能显著降低MKR小鼠的空腹血糖和INS水平(P<0.01);并能提高血清GLP-1浓度(P<0.01,P<0.05);上调小鼠结肠AMPK mRNA和P-AMPKα水平(P<0.01),下调UCP2 mRNA和蛋白水平(P<0.01)。白虎加人参汤低、高剂量组均能明显改善MKR小鼠结肠组织病理形态。结论白虎加人参汤可能通过抑制UCP2表达、激活AMPK的表达,促进肠道GLP-1的分泌,发挥治疗T2DM的作用。
文摘目的:系统评价长效胰高血糖素样肽-1(GLP-1)受体激动药索马鲁肽对比安慰剂或其他降糖药治疗2型糖尿病的疗效和安全性,为临床治疗提供循证参考。方法:计算机检索PubMed、Embase、Medline、Cochrane图书馆,检索时限为自建库起至2018年9月,收集索马鲁肽(试验组)对比安慰剂或其他降糖药(对照组)治疗2型糖尿病疗效和安全性的随机对照试验(RCT),对符合纳入标准的临床研究进行资料提取并采用Cochrane系统评价手册5.1.0进行质量评价后,使用Rev Man 5.3软件对治疗前后患者的糖化血红蛋白(HbA_1c)水平及达标率、空腹血糖(FPG)水平、收缩压、舒张压、体质量指数(BMI)、体质量、脉搏频率水平、低血糖和胃肠道反应发生率等指标进行Meta分析。结果:共纳入12项RCT,合计9 966例患者。Meta分析结果显示,试验组相比于对照组能更有效降低HbA_1c水平[MD=-1.03,95%CI(-1.22,-0.85),P<0.001]和FPG水平[MD=-1.14,95%CI(-1.53,-0.76),P<0.001],增加受试患者HbA_1c达标率[RD=0.40,95%CI(0.31,0.49),P<0.001],同时还可降低收缩压[MD=-2.61,95%CI(-3.23,-1.98),P<0.001]、舒张压[MD=-0.56,95%CI(-0.96,-0.16),P=0.006]、BMI[MD=-1.25,95%CI(-1.51,-0.99),P<0.001],减轻体质量[MD=-3.60,95%CI(-4.24,-2.96),P<0.001],增加脉搏频率[MD=2.16,95%CI(1.51,2.81),P<0.001],差异均有统计学意义;索马鲁肽的主要不良反应为胃肠道反应,其发生率高于对照组[RD=0.20,95%CI(0.15,0.26),P<0.001]、低血糖事件的发生率与对照组比较,差异则无统计学意义[RD=0.00,95%CI(-0.01,0.02),P=0.44]。结论:索马鲁肽可明显降低2型糖尿病患者的HbA_1c、FPG、体质量、血压水平,增加脉搏频率,提高服用患者的HbA_1c达标率;同时,虽然其致胃肠道反应发生率高于对照组,但不会增加低血糖发生的风险,提示该药具有较好的耐受性和安全性。
