罗格列酮对高糖培养肾小球系膜细胞胞外基质产生及降解的影响

目的:探讨罗格列酮(rosiglitazone maleate)对糖尿病肾病的保护机制。方法:大鼠肾小球系膜细胞分别培养在正常糖浓度(5.5mmol/L),高糖浓度(25mmol/L)及25mmol/L葡萄糖+20μmol/L罗格列酮的培养液中。CCK-8测定系膜细胞增殖;ELISA法检测培养上清液Ⅳ型胶原(Col-Ⅳ)、纤维连接蛋白(FN)、转化生长因子-β1(TGF-β1)、基质金属蛋白酶组织抑制因子-1(TIMP-1);明胶酶谱法检测培养上清液基质金属蛋白酶-2,9(MMP-2,9)的活性。结果:高糖组系膜细胞较正常对照组出现增殖增加,合成基质蛋白Col-Ⅳ、FN增多;MMP-2及MMP-9活性下降;TIMP-1含量增加;TGF-β1分泌增加。与高糖组比较,罗格列酮干预后能逆转上述变化。结论:罗格列酮能抑制高糖培养的系膜细胞增殖,减少胞外基质合成,增加胞外基质的降解。     

The effect of repaglinide on blood glucose and islet β-cell function in newly diagnosed type 2 diabetic patients

Objective To explore the effect of repaglinide intensive treatment on islet β-cell function and long-term control of blood glucose in newly diagnosed type 2 diabetic patients. Methods Self-control and inter-group control prospective study was conducted in 80 newly diagnosed type 2 diabetic patients who were treated with short-term repaglinide intensive treatment and islet β-cell function was assessed by 75 g oral glucose tolerance test (OGTT) before and after repaglinide treatment. The changes of △I30/△G30 ratio, blood lipid, HOMA A and HOMA B were examined. Results After treatment, in successful group, middle group and defeat group, the fasting plasma glucose levels were decreased from 8.9±1.5, 8.6±1.6,9.0±2.0 to 5.0±1.4,6.3±0. 7,6.5±0. 9 mmol/L, 0. 5 h postprandial glucose levels were decreased from (12.6±1.6, 12.6±1.5, 12.4±1.3 to 8.4±1.0, 6.8±0. 7, 8. 6±0. 9)mmol/L,and 2 h postprandial glucose levels were decreased from (13.0±1.2, 13. 1±1.3, 13. 3±1.4 to 9.2±0.9, 6.6±0. 7, 9.2±0. 9)mmol/L,respectively (all P <0. 005). The ratio of △I30/△G30 was increased froml. 69±0. 31, 1.72±0. 33, 1.79±0. 36 to 4. 47±0. 62, 4. 42±0.46,12. 00±0.46 in the three groups, respectively (P<0.05). HOMA B was significantly improved (P<0. 05), while triglycerides and HOMA A were decreased(P<0. 05). The levels of fasting blood glucose and postprandial blood glucose in 21 patients were maintained within normal range for more than six months. There were significant differences in the ratio of △I30/△G30, age, repaglinide dosage and the time of reaching target of glucose [4.47±0.62 vs. 2. 0± 0.46; 39±8 vs. 56±9; 2.0±1.5 vs. 5.0±2.5; 32.4±8.0 vs. 53.3±7.6; all P<0.05] between successful group and defeat group. Conclusions The short-term intensive treatment with repaglinide can significantly improve the early secretion phase of insulin and the islet β-cell function, reconstruct of the physiological model of insulin secretion and relieve the disease.     

The effect of repaglinide on blood glucose and islet β-cell function in newly diagnosed type 2 diabetic patients

Objective To explore the effect of repaglinide intensive treatment on islet β-cell function and long-term control of blood glucose in newly diagnosed type 2 diabetic patients. Methods Self-control and inter-group control prospective study was conducted in 80 newly diagnosed type 2 diabetic patients who were treated with short-term repaglinide intensive treatment and islet β-cell function was assessed by 75 g oral glucose tolerance test (OGTT) before and after repaglinide treatment. The changes of △I30/△G30 ratio, blood lipid, HOMA A and HOMA B were examined. Results After treatment, in successful group, middle group and defeat group, the fasting plasma glucose levels were decreased from 8.9±1.5, 8.6±1.6,9.0±2.0 to 5.0±1.4,6.3±0. 7,6.5±0. 9 mmol/L, 0. 5 h postprandial glucose levels were decreased from (12.6±1.6, 12.6±1.5, 12.4±1.3 to 8.4±1.0, 6.8±0. 7, 8. 6±0. 9)mmol/L,and 2 h postprandial glucose levels were decreased from (13.0±1.2, 13. 1±1.3, 13. 3±1.4 to 9.2±0.9, 6.6±0. 7, 9.2±0. 9)mmol/L,respectively (all P <0. 005). The ratio of △I30/△G30 was increased froml. 69±0. 31, 1.72±0. 33, 1.79±0. 36 to 4. 47±0. 62, 4. 42±0.46,12. 00±0.46 in the three groups, respectively (P<0.05). HOMA B was significantly improved (P<0. 05), while triglycerides and HOMA A were decreased(P<0. 05). The levels of fasting blood glucose and postprandial blood glucose in 21 patients were maintained within normal range for more than six months. There were significant differences in the ratio of △I30/△G30, age, repaglinide dosage and the time of reaching target of glucose [4.47±0.62 vs. 2. 0± 0.46; 39±8 vs. 56±9; 2.0±1.5 vs. 5.0±2.5; 32.4±8.0 vs. 53.3±7.6; all P<0.05] between successful group and defeat group. Conclusions The short-term intensive treatment with repaglinide can significantly improve the early secretion phase of insulin and the islet β-cell function, reconstruct of the physiological model of insulin secretion and relieve the disease.     

The effect of repaglinide on blood glucose and islet β-cell function in newly diagnosed type 2 diabetic patients

Objective To explore the effect of repaglinide intensive treatment on islet β-cell function and long-term control of blood glucose in newly diagnosed type 2 diabetic patients. Methods Self-control and inter-group control prospective study was conducted in 80 newly diagnosed type 2 diabetic patients who were treated with short-term repaglinide intensive treatment and islet β-cell function was assessed by 75 g oral glucose tolerance test (OGTT) before and after repaglinide treatment. The changes of △I30/△G30 ratio, blood lipid, HOMA A and HOMA B were examined. Results After treatment, in successful group, middle group and defeat group, the fasting plasma glucose levels were decreased from 8.9±1.5, 8.6±1.6,9.0±2.0 to 5.0±1.4,6.3±0. 7,6.5±0. 9 mmol/L, 0. 5 h postprandial glucose levels were decreased from (12.6±1.6, 12.6±1.5, 12.4±1.3 to 8.4±1.0, 6.8±0. 7, 8. 6±0. 9)mmol/L,and 2 h postprandial glucose levels were decreased from (13.0±1.2, 13. 1±1.3, 13. 3±1.4 to 9.2±0.9, 6.6±0. 7, 9.2±0. 9)mmol/L,respectively (all P <0. 005). The ratio of △I30/△G30 was increased froml. 69±0. 31, 1.72±0. 33, 1.79±0. 36 to 4. 47±0. 62, 4. 42±0.46,12. 00±0.46 in the three groups, respectively (P<0.05). HOMA B was significantly improved (P<0. 05), while triglycerides and HOMA A were decreased(P<0. 05). The levels of fasting blood glucose and postprandial blood glucose in 21 patients were maintained within normal range for more than six months. There were significant differences in the ratio of △I30/△G30, age, repaglinide dosage and the time of reaching target of glucose [4.47±0.62 vs. 2. 0± 0.46; 39±8 vs. 56±9; 2.0±1.5 vs. 5.0±2.5; 32.4±8.0 vs. 53.3±7.6; all P<0.05] between successful group and defeat group. Conclusions The short-term intensive treatment with repaglinide can significantly improve the early secretion phase of insulin and the islet β-cell function, reconstruct of the physiological model of insulin secretion and relieve the disease.     

普伐他汀对高糖培养肾小球系膜细胞细胞外基质产生和氧化应激的影响

目的探讨普伐他汀对糖尿病肾病的保护机制。方法大鼠肾小球系膜细胞分别用正常浓度葡萄糖(5.5 mmo.lL-1),高浓度葡萄糖(25 mmo.lL-1)及葡萄糖25 mmo.lL-1+普伐他汀100μmo.lL-1培养。用CCK-8试剂盒测定细胞增殖,比色法检测培养液中超氧化物歧化酶(SOD)活性、谷胱甘肽(GSH)和丙二醛(MDA)含量。ELISA法检测培养上清液Ⅳ型胶原(ColⅣ-)、纤连蛋白(FN)、转化生长因子β1(TGFβ-1)和基质金属蛋白酶组织抑制因子(TIMP-1)含量;明胶酶谱法检测培养上清明胶酶A及B的活性。结果与对照组比较,高糖组肾小球系膜细胞增殖增加,基质蛋白ColⅣ-和FN合成增多,明胶酶A及B活性下降,TIMP-1含量和TGFβ-1分泌增加,总SOD活性和Cu,Zn-SOD活性下降,GSH含量下降,MDA含量增加。与高糖组比较,普伐他汀干预后可逆转上述变化。结论普伐他汀可抑制高糖培养的肾小球系膜细胞增殖,减少胞外基质合成,增加胞外基质降解,并缓解高糖诱导的氧化应激。     

非诺贝特及罗格列酮对高糖培养肾小球系膜细胞p38MAPK信号通路调控影响

目的：探讨非诺贝特及罗格列酮对高糖培养大鼠肾小球系膜细胞（MC）p38丝裂原活化蛋白激酶（p38MAPK）信号传导通路的影响。方法：大鼠系膜细胞分别培养在正常糖浓度（5．5mmol／L）、高糖浓度（25mmol／L）、25mmol／L葡萄糖＋非诺贝特（FB）100μmol／L及25mmol／L葡萄糖＋罗格列酮（RG）20μmol／L。ELISA法检测培养细胞上清液Ⅳ型胶原（Col-Ⅳ）、纤维连接蛋白（FN）;Phospho—ELISA法检测胞浆及胞核内p38MAPK和磷酸化p38MAPK（p-p38MAPK）蛋白的表达：以及RT-PCR法检测p38MAPK的mRNA的表达。结果：与正常对照组比较,高糖组MC合成基质蛋白Col-Ⅳ、FN增多;胞浆及胞核内P—p38MAPK的表达增加。非诺贝特及罗格列酮干预能使高糖培养系膜细胞合成Col-Ⅳ、FN显著减少,胞核内p-p38MAPK表达显著下调,但对胞浆内p-p38MAPK的表达则无显著影响。各组总p38MAPK蛋白水平及p38MAPK的mRNA表达则没有明显改变。结论：非诺贝特及罗格列酮能够显著下调高糖培养的Mc核内p38MAPK信号传导通路的活化,进而减少胞外基质合成。     

非诺贝特对高糖培养肾小球系膜细胞胞外基质产生及降解影响

目的：探讨非诺贝特对糖尿病肾病的保护机制。方法：大鼠肾小球系膜细胞分别培养在正常糖浓度（5.5 mmol.L-1,对照组）、高糖浓度（25 mmol.L-1,高糖组）及25 mmol.L-1葡萄糖＋非诺贝特100μmol.L-1（非诺贝特组）。CCK-8测定系膜细胞增殖;ELISA法检测培养上清液Ⅳ型胶原（Col-Ⅳ）、纤维连接蛋白（FN）、转化生长因子-β1（TGF-β1）、基质金属蛋白酶组织抑制因子-1（TIMP-1）;明胶酶谱法检测培养上清基质金属蛋白酶-2,9（MMP-2,9）的活性。结果：高糖组系膜细胞较对照组出现增殖增加,合成基质蛋白Col-Ⅳ,FN增多,MMP-2及MMP-9活性下降,TIMP-1含量增加,TGF-β1分泌增加。与高糖组比较非诺贝特干预后能完全或部分逆转上述变化。结论：非诺贝特能抑制高糖培养的系膜细胞增殖,减少胞外基质合成,增加胞外基质的降解。     

瑞格列奈对新诊断2型糖尿病患者胰岛β细胞功能及血糖的影响

目的 探讨瑞格列奈短期强化治疗对改善新诊断2型糖尿病(T2DM)患者的胰岛β细胞功能及长期血糖控制的影响. 方法 采用自身前后对照和组间对照方法 ,观察80例空腹血糖(FPG)<11.1 mmol/L,餐后2 h血糖(PG2h)<15 mmol/L,糖化血红蛋白(HbA1c)<10.0%的新诊断T2DM患者接受瑞格列奈(诺和龙)短期强化治疗前后胰岛β细胞对血糖刺激的胰岛素早时相分泌(△I30/△G30比值)、血脂、胰岛素分泌(Homa)指数A、Homa B的变化. 结果 治疗后,75 g口服葡萄糖试验(OGTT)、成功组、中间组、失败组空腹血糖分别从(8.9±1.5)、(8.6±1.6)、(9.0±2.0)mmol/L降至(5.0±1.4)、(6.3±0.7)、(6.5±0.9)mmol/L,餐后0.5 h血糖分别从(12.6± 1.6)、(12.6±1.5)、(12.4±1.3)mmol/L降至(8.4±1.0)、(6.8±0.7)、(8.6±0.9)mmol/L,餐后2h血糖分别从(13.0±1.2)、(13.1±1.3)、(13.3±1.4)mmol/L降至(9.2±0.9)、(6.6±0.7)、(9.2±0.9)mmol/L,差异有统计学意义(P<0.005);△I30/△G30比值;成功组和中间组,失败组分别从1.69±0.31、1.72±0.33和平共处.79±0.36升高到4.47±0.62,4.42±0.46和2.00±0.46均有明显改善(P<0.05);Homa B明显升高(P<0.05),Homa A、三酰甘油(TG)明显下降(P<0.05).其中有21例患者超过6个月(最长达18个月)仅采用生活方式干预,空腹及餐后血糖均维持在正常范围;成功组与失败组相比,在△I30/△G30比值(4.47±0.62与2.0±0.46)、年龄((39±8)岁与(56±9岁)]、诺和龙最终用量[(2.0±1.5)g与(5.0±2.5)g3、血糖达标时间[(32.4±8.0)个月与(53.3±7.6)个月]比较差异均有统计学意义(P<0.05). 结论 短期瑞格列奈强化治疗可以恢复代表胰岛β细胞功能的血糖刺激的胰岛素早时相分泌,重塑胰岛素分泌的生理模式,有效缓解糖尿病病情.     

The effect of repaglinide on blood glucose and islet β-cell function in newly diagnosed type 2 diabetic patients

Objective To explore the effect of repaglinide intensive treatment on islet β-cell function and long-term control of blood glucose in newly diagnosed type 2 diabetic patients. Methods Self-control and inter-group control prospective study was conducted in 80 newly diagnosed type 2 diabetic patients who were treated with short-term repaglinide intensive treatment and islet β-cell function was assessed by 75 g oral glucose tolerance test (OGTT) before and after repaglinide treatment. The changes of △I30/△G30 ratio, blood lipid, HOMA A and HOMA B were examined. Results After treatment, in successful group, middle group and defeat group, the fasting plasma glucose levels were decreased from 8.9±1.5, 8.6±1.6,9.0±2.0 to 5.0±1.4,6.3±0. 7,6.5±0. 9 mmol/L, 0. 5 h postprandial glucose levels were decreased from (12.6±1.6, 12.6±1.5, 12.4±1.3 to 8.4±1.0, 6.8±0. 7, 8. 6±0. 9)mmol/L,and 2 h postprandial glucose levels were decreased from (13.0±1.2, 13. 1±1.3, 13. 3±1.4 to 9.2±0.9, 6.6±0. 7, 9.2±0. 9)mmol/L,respectively (all P <0. 005). The ratio of △I30/△G30 was increased froml. 69±0. 31, 1.72±0. 33, 1.79±0. 36 to 4. 47±0. 62, 4. 42±0.46,12. 00±0.46 in the three groups, respectively (P<0.05). HOMA B was significantly improved (P<0. 05), while triglycerides and HOMA A were decreased(P<0. 05). The levels of fasting blood glucose and postprandial blood glucose in 21 patients were maintained within normal range for more than six months. There were significant differences in the ratio of △I30/△G30, age, repaglinide dosage and the time of reaching target of glucose [4.47±0.62 vs. 2. 0± 0.46; 39±8 vs. 56±9; 2.0±1.5 vs. 5.0±2.5; 32.4±8.0 vs. 53.3±7.6; all P<0.05] between successful group and defeat group. Conclusions The short-term intensive treatment with repaglinide can significantly improve the early secretion phase of insulin and the islet β-cell function, reconstruct of the physiological model of insulin secretion and relieve the disease.     

The effect of repaglinide on blood glucose and islet β-cell function in newly diagnosed type 2 diabetic patients

Objective To explore the effect of repaglinide intensive treatment on islet β-cell function and long-term control of blood glucose in newly diagnosed type 2 diabetic patients. Methods Self-control and inter-group control prospective study was conducted in 80 newly diagnosed type 2 diabetic patients who were treated with short-term repaglinide intensive treatment and islet β-cell function was assessed by 75 g oral glucose tolerance test (OGTT) before and after repaglinide treatment. The changes of △I30/△G30 ratio, blood lipid, HOMA A and HOMA B were examined. Results After treatment, in successful group, middle group and defeat group, the fasting plasma glucose levels were decreased from 8.9±1.5, 8.6±1.6,9.0±2.0 to 5.0±1.4,6.3±0. 7,6.5±0. 9 mmol/L, 0. 5 h postprandial glucose levels were decreased from (12.6±1.6, 12.6±1.5, 12.4±1.3 to 8.4±1.0, 6.8±0. 7, 8. 6±0. 9)mmol/L,and 2 h postprandial glucose levels were decreased from (13.0±1.2, 13. 1±1.3, 13. 3±1.4 to 9.2±0.9, 6.6±0. 7, 9.2±0. 9)mmol/L,respectively (all P <0. 005). The ratio of △I30/△G30 was increased froml. 69±0. 31, 1.72±0. 33, 1.79±0. 36 to 4. 47±0. 62, 4. 42±0.46,12. 00±0.46 in the three groups, respectively (P<0.05). HOMA B was significantly improved (P<0. 05), while triglycerides and HOMA A were decreased(P<0. 05). The levels of fasting blood glucose and postprandial blood glucose in 21 patients were maintained within normal range for more than six months. There were significant differences in the ratio of △I30/△G30, age, repaglinide dosage and the time of reaching target of glucose [4.47±0.62 vs. 2. 0± 0.46; 39±8 vs. 56±9; 2.0±1.5 vs. 5.0±2.5; 32.4±8.0 vs. 53.3±7.6; all P<0.05] between successful group and defeat group. Conclusions The short-term intensive treatment with repaglinide can significantly improve the early secretion phase of insulin and the islet β-cell function, reconstruct of the physiological model of insulin secretion and relieve the disease.