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
目的探讨Glucagon like peptide-1 receptor(GLP-1R)对脓毒症急性肾损伤(AKI)炎症反应及细胞凋亡的影响及其可能机制。方法通过盲肠结扎穿孔(CLP)法建立AKI模型。30只小鼠随机分为五组:对照组:小鼠建立假模型后接受溶剂处理;药物对照组...目的探讨Glucagon like peptide-1 receptor(GLP-1R)对脓毒症急性肾损伤(AKI)炎症反应及细胞凋亡的影响及其可能机制。方法通过盲肠结扎穿孔(CLP)法建立AKI模型。30只小鼠随机分为五组:对照组:小鼠建立假模型后接受溶剂处理;药物对照组:小鼠建立假模型接受GLP-1R激动剂利拉鲁肽(2 mg/kg)处理;模型组:小鼠建立AKI模型接受溶剂处理;治疗组:小鼠建立AKI模型后利拉鲁肽(2 mg/kg)处理;抑制剂组:小鼠建立AKI模型后接受利拉鲁肽(2 mg/kg)及silent mating type information regulation2 homolog-3(SIRT3)抑制剂3-TYP(5 mg/kg)处理。Western blot法检测SIRT3蛋白表达。酶联免疫法检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6水平。自动生化分析仪检测血清肌酐及尿素氮水平。TUNEL染色法检测肾组织细胞凋亡。结果与对照组比较,模型组SIRT3表达及活性分别显著下降为(70.1±4.5)%及(73.7±5.3)%,血清TNF-α、IL-1β、IL-6、肌酐、尿素氮及肾细胞凋亡分别显著增加为(359.8±36.5)pg/mL、(290.0±26.7)pg/mL、(852.3±41.0)ng/mL、(59.0±8.7)μmol/L、(25.2±7.0)mmol/L、(49.0±9.3)个/视野,差异均有统计学意义(P<0.05)。与模型组比较,治疗组SIRT3表达及活性显著增加为(87.0±6.4)%及(85.4±7.3)%,血清TNF-α、IL-1β、IL-6、肌酐、尿素氮及肾细胞凋亡分别显著下降为(282.7±16.9)pg/mL、(189.0±14.2)pg/mL、(461.2±34.0)ng/mL、(38.7±5.9)μmol/L、(17.7±2.9)mmol/L、(21.0±5.2)个/视野,差异均有统计学意义(P<0.05)。与治疗组比较,抑制剂组血清TNF-α、IL-1β、IL-6、肌酐、尿素氮及肾细胞凋亡分别显著增加为(347.8±30.6)pg/mL、(265.9±28.5)pg/mL、(838.7±34.9)ng/mL、(57.5±7.2)μmol/L、(26.8±4.7)mmol/L、(47.0±12.0)个/视野,差异均有统计学意义(P<0.05)。结论激活GLP-1R可以显著抑制脓毒症AKI中炎症反应及细胞凋亡,改善肾功能,其机制与上调SIRT3表达有关。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。
文摘目的探讨Glucagon like peptide-1 receptor(GLP-1R)对脓毒症急性肾损伤(AKI)炎症反应及细胞凋亡的影响及其可能机制。方法通过盲肠结扎穿孔(CLP)法建立AKI模型。30只小鼠随机分为五组:对照组:小鼠建立假模型后接受溶剂处理;药物对照组:小鼠建立假模型接受GLP-1R激动剂利拉鲁肽(2 mg/kg)处理;模型组:小鼠建立AKI模型接受溶剂处理;治疗组:小鼠建立AKI模型后利拉鲁肽(2 mg/kg)处理;抑制剂组:小鼠建立AKI模型后接受利拉鲁肽(2 mg/kg)及silent mating type information regulation2 homolog-3(SIRT3)抑制剂3-TYP(5 mg/kg)处理。Western blot法检测SIRT3蛋白表达。酶联免疫法检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6水平。自动生化分析仪检测血清肌酐及尿素氮水平。TUNEL染色法检测肾组织细胞凋亡。结果与对照组比较,模型组SIRT3表达及活性分别显著下降为(70.1±4.5)%及(73.7±5.3)%,血清TNF-α、IL-1β、IL-6、肌酐、尿素氮及肾细胞凋亡分别显著增加为(359.8±36.5)pg/mL、(290.0±26.7)pg/mL、(852.3±41.0)ng/mL、(59.0±8.7)μmol/L、(25.2±7.0)mmol/L、(49.0±9.3)个/视野,差异均有统计学意义(P<0.05)。与模型组比较,治疗组SIRT3表达及活性显著增加为(87.0±6.4)%及(85.4±7.3)%,血清TNF-α、IL-1β、IL-6、肌酐、尿素氮及肾细胞凋亡分别显著下降为(282.7±16.9)pg/mL、(189.0±14.2)pg/mL、(461.2±34.0)ng/mL、(38.7±5.9)μmol/L、(17.7±2.9)mmol/L、(21.0±5.2)个/视野,差异均有统计学意义(P<0.05)。与治疗组比较,抑制剂组血清TNF-α、IL-1β、IL-6、肌酐、尿素氮及肾细胞凋亡分别显著增加为(347.8±30.6)pg/mL、(265.9±28.5)pg/mL、(838.7±34.9)ng/mL、(57.5±7.2)μmol/L、(26.8±4.7)mmol/L、(47.0±12.0)个/视野,差异均有统计学意义(P<0.05)。结论激活GLP-1R可以显著抑制脓毒症AKI中炎症反应及细胞凋亡,改善肾功能,其机制与上调SIRT3表达有关。
