利拉鲁肽对Ⅲ型腺苷酸环化酶表达的影响及其在胰岛素抵抗和肥胖中的作用
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摘要
目的：
1、探讨胰高血糖素样肽-1(glucagon-like peptide-1, GLP-1)类似物利拉鲁肽(liragrutide)对肥胖非糖尿病小鼠和糖尿病肥胖小鼠血糖和体重的影响,并研究其作用与胰岛素敏感组织中工Ⅲ型腺苷酸环化酶(adenylyl cyclase3, AC3)基因和蛋白表达水平的关系。
2、探讨利拉鲁肽对肥胖和非肥胖2型糖尿病患者血AC3、糖代谢、体重和胰岛素抵抗的影响,以及AC3和胰岛素抵抗(insulin resistance, IR)及肥胖的相关性。
3、观察利拉鲁肽对脐静脉内皮细胞(human umbilical vein endothelial cell, HUVECs) AC3表达的影响。
方法：
1、动物实验：选取C57BL/6J小、鼠和db/db基因鼠(2型糖尿病肥胖模型)。C57BL/6J小鼠随机分为3组(C57普料组、C57高脂干预组和C57高脂未干预组),每组8只,每实验组雌雄配对：两实验组C57BL/6J小鼠给予高脂饲料(含34.9g%的脂肪和26.2g％蛋白质)为C57高脂干预组和C57高脂未干预组,另一实验组C57BL小鼠给予普通饲料(4.5g%的脂肪和4.5g%蛋白质)为C57普料组。db/db小鼠16只,分为2组(db干预组和db未干预组),每组8只,每实验组雌雄配对。每周测量体重和尾静脉随机血糖。从第12周开始,一组肥胖C57BL/6J小鼠即C57高脂干预组和db干预组小鼠给予皮下注射利拉鲁肽100μg/kg,每日两次,其余三组给予等量生理盐水作为对照,进行12周后摘取眼球采内眦静脉血,迅速取出脂肪、肝脏、肌肉、大小肠连接处组织,行TaqMan Realtime PCR技术检测组织细胞AC3mRNA的表达和蛋白免疫印迹法Western blot技术检测组织细胞AC3蛋白的表达。静脉血离心取上清液行胰岛素检测。
2、临床部分：按照标准选取NGT组32例和T2DM组25例,再根据体质指数(BMI)分为2个亚组,BMI≥28Kg/m2为肥胖组；18.5Kg/m2≤BMI<24Kg/m2为非肥胖组。NGT肥胖组15例,男8例,女7例,NGT非肥胖组17例,男9例,女8例；T2DM肥胖组12例,男6例,女6例,T2DM非肥胖组13例,男7例,女6例。T2DM组给予利拉鲁肽0.6mg每日一次,皮下注射,1周后加量至1.2mg,连续16周,NGT肥胖组予以健康教育。所有研究对象清晨空腹检测以下指标,身高(m)、体重(kg)、体质指数(BMI)、腰臀比(WHR)、空腹血糖、HbAic、HDL-C、TG、TC和LDL-C、AC3水平,计算HOMA-IR;每4周随访一次,共随访16周。
3、细胞实验：分别用不同浓度的利拉鲁肽(0、10、100nmol/L)处理HUVECs8h、24h后抽提总RNA,用半定量逆转录聚合酶链反应(RT-PCR)技术及Western blot方法检测AC3mRNA及蛋白的表达。
结果：
1、动物部分：利拉鲁肽能显著促进肥胖非糖尿病小鼠和肥胖糖尿病小鼠AC3mRNA和蛋白的表达,减轻体重,改善血糖(p＜0.01)。利拉鲁肽治疗12周,db/db小鼠,与未干预组比较,干预组体重、血糖均下降,胰岛素升高,差异均有统计学意义(P＜0.05)。C57BL/6J小鼠3组间血糖无差异；C57高脂无干预组与C57普料组比较,体重、胰岛素明显增加,差异有统计学意义(P＜0.05)；C57高脂干预组与高脂未干预组比较,体重、胰岛素明显减低,差异有统计学意义(P＜0.05)。各组小鼠脂肪细胞、肝脏、骨骼肌、大小肠连接处AC3mRNA表达的比较：db/db小鼠,干预组较未干预组AC3mRNA表达明显增加,差异均有统计学意义(P<0.05)。C57BL小鼠,与普通饲料无干预组比较,高脂未干预组AC3mRNA表达明显减低,差异有统计学意义(P＜0.05)；高脂干预组AC3mRNA表达明显增加有统计学意义(P＜0.05)。
2、临床部分：(1)T2DM非肥胖组：利拉鲁肽治疗16周后FPG、HbA1C、 HOMA-IR和胰岛素水平下降有统计学意义(P<0.05), HDL-C、AC3升高有显著意义(P<0.05)。(2)T2DM肥胖组：利拉鲁肽治疗后体重、BMI、WHR、 FPG、HbA1、胰岛素、HOMA-IR值显著降低(P<0.05), TC、HDL-C、AC3较治疗前升高(分别为P<0.05, P<0.01)。(3)T2DM肥胖组体重、BMI、WHR下降较非肥胖组显著(分别为P<0.01,P<0.05),AC3升高有显著意义(P＜0.01)。(4)统计相关分析显示：AC3与体重、BMI、WHR、HOMA-IR呈负相关(分别为r=-0.254, P<0.01, r=-0.228、P<0.05, r=-0.703、P<0.01, r=-0.212、P<0.05)。利拉鲁肽治疗后效果,FPG下降与治疗前FPG、HbA1c、 HOMA-IR呈正相关(分别为r=0.914、P<0.01, r=0.771、P<0.01, r=0.194, P<0.05),Stepwise多元逐步回归分析示AC3升高与治疗前治疗前体重、BMI、 HOMA-IR呈负相关,与治疗前AC3水平正相关；以AC3为因变量,体重、BMI、 WHR、HOMA-IR、FPG、HbA1c、TG、TC、HDL-C和LDL-C为自变量进行多元逐步回归分析,结果显示体重、BMI、WHR、HOMA-IR最后进入回归方程,方程校正后r2=0.542,P=0.001。
3、利拉鲁肽(10nmol/l)干预8小时、24小时的AC3mRNA表达均有显著意义(P＜0.01),内皮细胞AC3蛋白表达随着时间的延长而呈上升趋势(P＜0.01)。利拉鲁肽和HUVECs共培养24小时后,随着GLP-1浓度(0、10、100nmol/L)的增加,AC3mRNA表达水平明显增加(P＜0.01),蛋白表达水平明显上升(P＜0.01),NaN3对AC3的表达没有影响。
结论：
1、AC3与体重、BMI、WHR、HOMA-IR呈负相关,利拉鲁肽干预后可以增加AC3的水平,不论是实验动物还是患者的高体重和胰岛素抵抗可以通过利拉鲁肽的干预来逆转。
2、利拉鲁肽对HUVECs AC3表达的影响显示AC3的表达随着利拉鲁肽的浓度以及时间的延长而呈上升趋势。
objective:
1.To investigate the effects of liraglutide on expression of adenylyl cyclase3in C57BL rat and diabetes rat.
2.To investigate the effect of liraglutide on the levels of HOMA-IR and the adenylyl cyclase3in type2diabetes with or without obesity.
3.To investigate the effects of liraglutide on expression of adenylyl cyclase3in human umbilical vein endothelial cells.
Methods:
1.Animal experiment:select twenty-fourC57BL/6J mice and sixteen db/db gene (obese rat model of type2diabetes). C57BL/6J mice were randomly divided into3groups (C57normal diet group, C57high fat feeding without intervention group and C57high fat feeding intervention group), with8rats in each group, and each experimental group of male and female pair:two experimental group C57BL/6J mice fed a high fat diet (34.9g%containing fat and protein26.2g%) for the C57high lipid intervention group and C57fat non-intervention group, in another experiment groups of C57BL mice were given normal diet (4.5g%fat and14.5g%protein) for C57material.16db/db mice, divided into2groups (DB intervention group and without DB intervention group), with8rats in each group, and each experimental group of male and female mating. Weekly measurements of body weight and tail vein blood glucose. From the beginning of the twelfth week, C57high-fat intervention group and DB intervention group mice were given subcutaneous injection of liraglutide100μg/kg, two times a day, the other three groups received normal saline as a control,12weeks after removal of eyeball mining angular vein blood, quickly remove the fat, liver, muscle, large intestine joint tissue, expression of TaqMan Realtime PCR for the detection of cell AC3mRNA expression and protein immunoblotting detection of Western in blot cells AC3protein. Venous blood centrifugation supernatant insulin detection.
2.Clinical part:according to the standard of selecting32cases in NGT group and T2DM group25cases, according to the body mass index (BMI) were divided into2subgroups, BMI≥28Kg/m2as obesity group;18.5Kg/m2=BMI<24Kg/m2for non obese group. NGT obesity group15cases, male8cases, female7cases, NGT non obese group17cases, male9cases, female8cases; T2DM obesity group12cases, male6cases, female6cases, T2DM non obese group13cases, male7cases, female6cases. T2DM group received liraglutide0.6mg once daily, subcutaneous injection,1weeks after added to1.2mg, for16weeks, NGT obesity group were given health education. All of the subjects under fasting detection index, height (m), body weight (kg), body mass index (BMI), waist hip ratio(WHR), fasting blood glucose,HbA1C,HDL-C,TG,TC and LDL-C,AC3level,HOMA-IR; followed up every4weeks,a total of16weeks of follow-up.
3.HUVEC were cocultured with different concentration of liraglutide (0,10,100nmol/L) for8h or24h. Extraction of total RNA,AC3protein and mRNA expression in HUVECs were measured by Western bloting and reverse transcription polymerase chain reaction(RT-PCR)
Results
1. Animal parts:liraglutide significantly promote obese non-diabetic mice and obese the diabetic mice AC3mRNA and the protein expression,decrease weight,improve blood glucose(p<0.01). Liraglutide12weeks of treatment, db/db mice,with and without intervention group compared to the intervention group, weight,blood glucose decreased and insulin rises,the differences were statistically significant (P<0.05). No difference in C57BL/6J mice among the three groups glucose; C57high-fat intervention group and the C57normal diet group,body weight,insulin significantly increased,the difference was statistically significant (P<0.05);C57high-fat intervention group and high-fat without intervention group,body weight,insulin was significantly reduced,and the difference was statistically significant (P<0.05). Each group of mice fat cells, liver, skeletal muscle, the junction of large intestine and small intestine AC3mRNA expression comparison:db/db mice, the intervention group than non-intervention group AC3mRNA expression was significantly increased, and the differences were statistically significant (P<0.05). C57BL mice fat without intervention group AC3mRNA expression was significantly reduced, the difference was statistically significant (P<0.05); the high fat intervention group AC3mRNA expression was significantly increased statistically significant (P<0.05).
2. Clinical part:(1) T2DM non-obese group:FPG,HbA1C,HOMA-IR and insulin levels of liraglutide after16weeks of treatment was statistically significant (P<0.05),HDL-C,AC3significant increased(P<0.05).(2) T2DM obese group: weight,BMI,WHR,FPG,HbA1C,insulin,HOMA-IR value liraglutide after treatment was significantly lower (P<0.05), TC, HDL-C, AC3higher than before treatment (respectively P<0.05, P<0.01).(3) T2DM obesity group, body weight, BMI, WHR decline than non-obese group was significantly (respectively, P<0.01, P<0.05), AC3increased there was a significant (P<0.01).(4) Statistical analysis showed that:the AC3with weight, BMI, WHR, of HOMA-IR was negatively correlated (r=-0.254,respectively,P<0.01, r=-0.228, P<0.05, r=-0.703, P<0.01,r=-0.212,P<0.05).Liraglutide treatment effect,FPG decreased pre-treatment FPG, HbA1C,HOMA-IR was positively correlated (r=0.914, respectively, P<0.01, r=0.771, P<0.01, r=0.194, P<0.05), Stepwise multiple stepwise regression analysis shows the AC3elevated treatment before treatment before weight, BMI, HOMA-IR was negatively correlated with pre-treatment AC3level of positive correlation; AC3for the dependent variable, body weight, BMI,WHR, HOMA-IR, FPG HbA1C, TG, TC, HDL-C and LDL-C as the independent variable stepwise multiple regression analysis, the results showed that body weight,BMI,WHR,HOMA-IR last into the regression equation, equation corrected r2=0.542, P=0.001.
3.Liraglutide(10nmol/l) intervention in8hours,24hours AC3mRNA were significant (P<0.01),the endothelial cells expression in an upward trend with time (P<0.01).Liraglutide and HUVECs were cultured for24hours,with the liraglutide concentration (0,10,100nmol/L) increased, AC3mRNA expression levels were significantly increased (P<0.01) and protein expression levels were significantly increased (P<0.01),while NaN3has no effect on the expression of the AC3.
Conclusions
1.AC3was negatively correlated with body weight, BMI, WHR, HOMA-IR, liraglutide treatment can increase the AC3level, whether animal or in patients with high body weight and insulin resistance can be reversed by liraglutide intervention.
2.Effects of liraglutide on expression of HUVECs in AC3display with the concentration of liraglutide and prolong the time of increased expression of AC3.
1、探讨胰高血糖素样肽-1(glucagon-like peptide-1, GLP-1)类似物利拉鲁肽(liragrutide)对肥胖非糖尿病小鼠和糖尿病肥胖小鼠血糖和体重的影响,并研究其作用与胰岛素敏感组织中工Ⅲ型腺苷酸环化酶(adenylyl cyclase3, AC3)基因和蛋白表达水平的关系。
2、探讨利拉鲁肽对肥胖和非肥胖2型糖尿病患者血AC3、糖代谢、体重和胰岛素抵抗的影响,以及AC3和胰岛素抵抗(insulin resistance, IR)及肥胖的相关性。
3、观察利拉鲁肽对脐静脉内皮细胞(human umbilical vein endothelial cell, HUVECs) AC3表达的影响。
方法：
1、动物实验：选取C57BL/6J小、鼠和db/db基因鼠(2型糖尿病肥胖模型)。C57BL/6J小鼠随机分为3组(C57普料组、C57高脂干预组和C57高脂未干预组),每组8只,每实验组雌雄配对：两实验组C57BL/6J小鼠给予高脂饲料(含34.9g%的脂肪和26.2g％蛋白质)为C57高脂干预组和C57高脂未干预组,另一实验组C57BL小鼠给予普通饲料(4.5g%的脂肪和4.5g%蛋白质)为C57普料组。db/db小鼠16只,分为2组(db干预组和db未干预组),每组8只,每实验组雌雄配对。每周测量体重和尾静脉随机血糖。从第12周开始,一组肥胖C57BL/6J小鼠即C57高脂干预组和db干预组小鼠给予皮下注射利拉鲁肽100μg/kg,每日两次,其余三组给予等量生理盐水作为对照,进行12周后摘取眼球采内眦静脉血,迅速取出脂肪、肝脏、肌肉、大小肠连接处组织,行TaqMan Realtime PCR技术检测组织细胞AC3mRNA的表达和蛋白免疫印迹法Western blot技术检测组织细胞AC3蛋白的表达。静脉血离心取上清液行胰岛素检测。
2、临床部分：按照标准选取NGT组32例和T2DM组25例,再根据体质指数(BMI)分为2个亚组,BMI≥28Kg/m2为肥胖组；18.5Kg/m2≤BMI<24Kg/m2为非肥胖组。NGT肥胖组15例,男8例,女7例,NGT非肥胖组17例,男9例,女8例；T2DM肥胖组12例,男6例,女6例,T2DM非肥胖组13例,男7例,女6例。T2DM组给予利拉鲁肽0.6mg每日一次,皮下注射,1周后加量至1.2mg,连续16周,NGT肥胖组予以健康教育。所有研究对象清晨空腹检测以下指标,身高(m)、体重(kg)、体质指数(BMI)、腰臀比(WHR)、空腹血糖、HbAic、HDL-C、TG、TC和LDL-C、AC3水平,计算HOMA-IR;每4周随访一次,共随访16周。
3、细胞实验：分别用不同浓度的利拉鲁肽(0、10、100nmol/L)处理HUVECs8h、24h后抽提总RNA,用半定量逆转录聚合酶链反应(RT-PCR)技术及Western blot方法检测AC3mRNA及蛋白的表达。
结果：
1、动物部分：利拉鲁肽能显著促进肥胖非糖尿病小鼠和肥胖糖尿病小鼠AC3mRNA和蛋白的表达,减轻体重,改善血糖(p＜0.01)。利拉鲁肽治疗12周,db/db小鼠,与未干预组比较,干预组体重、血糖均下降,胰岛素升高,差异均有统计学意义(P＜0.05)。C57BL/6J小鼠3组间血糖无差异；C57高脂无干预组与C57普料组比较,体重、胰岛素明显增加,差异有统计学意义(P＜0.05)；C57高脂干预组与高脂未干预组比较,体重、胰岛素明显减低,差异有统计学意义(P＜0.05)。各组小鼠脂肪细胞、肝脏、骨骼肌、大小肠连接处AC3mRNA表达的比较：db/db小鼠,干预组较未干预组AC3mRNA表达明显增加,差异均有统计学意义(P<0.05)。C57BL小鼠,与普通饲料无干预组比较,高脂未干预组AC3mRNA表达明显减低,差异有统计学意义(P＜0.05)；高脂干预组AC3mRNA表达明显增加有统计学意义(P＜0.05)。
2、临床部分：(1)T2DM非肥胖组：利拉鲁肽治疗16周后FPG、HbA1C、 HOMA-IR和胰岛素水平下降有统计学意义(P<0.05), HDL-C、AC3升高有显著意义(P<0.05)。(2)T2DM肥胖组：利拉鲁肽治疗后体重、BMI、WHR、 FPG、HbA1、胰岛素、HOMA-IR值显著降低(P<0.05), TC、HDL-C、AC3较治疗前升高(分别为P<0.05, P<0.01)。(3)T2DM肥胖组体重、BMI、WHR下降较非肥胖组显著(分别为P<0.01,P<0.05),AC3升高有显著意义(P＜0.01)。(4)统计相关分析显示：AC3与体重、BMI、WHR、HOMA-IR呈负相关(分别为r=-0.254, P<0.01, r=-0.228、P<0.05, r=-0.703、P<0.01, r=-0.212、P<0.05)。利拉鲁肽治疗后效果,FPG下降与治疗前FPG、HbA1c、 HOMA-IR呈正相关(分别为r=0.914、P<0.01, r=0.771、P<0.01, r=0.194, P<0.05),Stepwise多元逐步回归分析示AC3升高与治疗前治疗前体重、BMI、 HOMA-IR呈负相关,与治疗前AC3水平正相关；以AC3为因变量,体重、BMI、 WHR、HOMA-IR、FPG、HbA1c、TG、TC、HDL-C和LDL-C为自变量进行多元逐步回归分析,结果显示体重、BMI、WHR、HOMA-IR最后进入回归方程,方程校正后r2=0.542,P=0.001。
3、利拉鲁肽(10nmol/l)干预8小时、24小时的AC3mRNA表达均有显著意义(P＜0.01),内皮细胞AC3蛋白表达随着时间的延长而呈上升趋势(P＜0.01)。利拉鲁肽和HUVECs共培养24小时后,随着GLP-1浓度(0、10、100nmol/L)的增加,AC3mRNA表达水平明显增加(P＜0.01),蛋白表达水平明显上升(P＜0.01),NaN3对AC3的表达没有影响。
结论：
1、AC3与体重、BMI、WHR、HOMA-IR呈负相关,利拉鲁肽干预后可以增加AC3的水平,不论是实验动物还是患者的高体重和胰岛素抵抗可以通过利拉鲁肽的干预来逆转。
2、利拉鲁肽对HUVECs AC3表达的影响显示AC3的表达随着利拉鲁肽的浓度以及时间的延长而呈上升趋势。
objective:
1.To investigate the effects of liraglutide on expression of adenylyl cyclase3in C57BL rat and diabetes rat.
2.To investigate the effect of liraglutide on the levels of HOMA-IR and the adenylyl cyclase3in type2diabetes with or without obesity.
3.To investigate the effects of liraglutide on expression of adenylyl cyclase3in human umbilical vein endothelial cells.
Methods:
1.Animal experiment:select twenty-fourC57BL/6J mice and sixteen db/db gene (obese rat model of type2diabetes). C57BL/6J mice were randomly divided into3groups (C57normal diet group, C57high fat feeding without intervention group and C57high fat feeding intervention group), with8rats in each group, and each experimental group of male and female pair:two experimental group C57BL/6J mice fed a high fat diet (34.9g%containing fat and protein26.2g%) for the C57high lipid intervention group and C57fat non-intervention group, in another experiment groups of C57BL mice were given normal diet (4.5g%fat and14.5g%protein) for C57material.16db/db mice, divided into2groups (DB intervention group and without DB intervention group), with8rats in each group, and each experimental group of male and female mating. Weekly measurements of body weight and tail vein blood glucose. From the beginning of the twelfth week, C57high-fat intervention group and DB intervention group mice were given subcutaneous injection of liraglutide100μg/kg, two times a day, the other three groups received normal saline as a control,12weeks after removal of eyeball mining angular vein blood, quickly remove the fat, liver, muscle, large intestine joint tissue, expression of TaqMan Realtime PCR for the detection of cell AC3mRNA expression and protein immunoblotting detection of Western in blot cells AC3protein. Venous blood centrifugation supernatant insulin detection.
2.Clinical part:according to the standard of selecting32cases in NGT group and T2DM group25cases, according to the body mass index (BMI) were divided into2subgroups, BMI≥28Kg/m2as obesity group;18.5Kg/m2=BMI<24Kg/m2for non obese group. NGT obesity group15cases, male8cases, female7cases, NGT non obese group17cases, male9cases, female8cases; T2DM obesity group12cases, male6cases, female6cases, T2DM non obese group13cases, male7cases, female6cases. T2DM group received liraglutide0.6mg once daily, subcutaneous injection,1weeks after added to1.2mg, for16weeks, NGT obesity group were given health education. All of the subjects under fasting detection index, height (m), body weight (kg), body mass index (BMI), waist hip ratio(WHR), fasting blood glucose,HbA1C,HDL-C,TG,TC and LDL-C,AC3level,HOMA-IR; followed up every4weeks,a total of16weeks of follow-up.
3.HUVEC were cocultured with different concentration of liraglutide (0,10,100nmol/L) for8h or24h. Extraction of total RNA,AC3protein and mRNA expression in HUVECs were measured by Western bloting and reverse transcription polymerase chain reaction(RT-PCR)
Results
1. Animal parts:liraglutide significantly promote obese non-diabetic mice and obese the diabetic mice AC3mRNA and the protein expression,decrease weight,improve blood glucose(p<0.01). Liraglutide12weeks of treatment, db/db mice,with and without intervention group compared to the intervention group, weight,blood glucose decreased and insulin rises,the differences were statistically significant (P<0.05). No difference in C57BL/6J mice among the three groups glucose; C57high-fat intervention group and the C57normal diet group,body weight,insulin significantly increased,the difference was statistically significant (P<0.05);C57high-fat intervention group and high-fat without intervention group,body weight,insulin was significantly reduced,and the difference was statistically significant (P<0.05). Each group of mice fat cells, liver, skeletal muscle, the junction of large intestine and small intestine AC3mRNA expression comparison:db/db mice, the intervention group than non-intervention group AC3mRNA expression was significantly increased, and the differences were statistically significant (P<0.05). C57BL mice fat without intervention group AC3mRNA expression was significantly reduced, the difference was statistically significant (P<0.05); the high fat intervention group AC3mRNA expression was significantly increased statistically significant (P<0.05).
2. Clinical part:(1) T2DM non-obese group:FPG,HbA1C,HOMA-IR and insulin levels of liraglutide after16weeks of treatment was statistically significant (P<0.05),HDL-C,AC3significant increased(P<0.05).(2) T2DM obese group: weight,BMI,WHR,FPG,HbA1C,insulin,HOMA-IR value liraglutide after treatment was significantly lower (P<0.05), TC, HDL-C, AC3higher than before treatment (respectively P<0.05, P<0.01).(3) T2DM obesity group, body weight, BMI, WHR decline than non-obese group was significantly (respectively, P<0.01, P<0.05), AC3increased there was a significant (P<0.01).(4) Statistical analysis showed that:the AC3with weight, BMI, WHR, of HOMA-IR was negatively correlated (r=-0.254,respectively,P<0.01, r=-0.228, P<0.05, r=-0.703, P<0.01,r=-0.212,P<0.05).Liraglutide treatment effect,FPG decreased pre-treatment FPG, HbA1C,HOMA-IR was positively correlated (r=0.914, respectively, P<0.01, r=0.771, P<0.01, r=0.194, P<0.05), Stepwise multiple stepwise regression analysis shows the AC3elevated treatment before treatment before weight, BMI, HOMA-IR was negatively correlated with pre-treatment AC3level of positive correlation; AC3for the dependent variable, body weight, BMI,WHR, HOMA-IR, FPG HbA1C, TG, TC, HDL-C and LDL-C as the independent variable stepwise multiple regression analysis, the results showed that body weight,BMI,WHR,HOMA-IR last into the regression equation, equation corrected r2=0.542, P=0.001.
3.Liraglutide(10nmol/l) intervention in8hours,24hours AC3mRNA were significant (P<0.01),the endothelial cells expression in an upward trend with time (P<0.01).Liraglutide and HUVECs were cultured for24hours,with the liraglutide concentration (0,10,100nmol/L) increased, AC3mRNA expression levels were significantly increased (P<0.01) and protein expression levels were significantly increased (P<0.01),while NaN3has no effect on the expression of the AC3.
Conclusions
1.AC3was negatively correlated with body weight, BMI, WHR, HOMA-IR, liraglutide treatment can increase the AC3level, whether animal or in patients with high body weight and insulin resistance can be reversed by liraglutide intervention.
2.Effects of liraglutide on expression of HUVECs in AC3display with the concentration of liraglutide and prolong the time of increased expression of AC3.
引文
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