中华内分泌代谢杂志
中華內分泌代謝雜誌
중화내분비대사잡지
CHINESE JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2010年
10期
871-874
,共4页
张志红%杨刚毅%李伶%刘瑞%李钶%李生兵%陈文雯%朱伟%Guenther Boden
張誌紅%楊剛毅%李伶%劉瑞%李鈳%李生兵%陳文雯%硃偉%Guenther Boden
장지홍%양강의%리령%류서%리아%리생병%진문문%주위%Guenther Boden
利拉鲁肽%RNA干扰%脂联素%胰岛素抵抗%糖脂代谢
利拉魯肽%RNA榦擾%脂聯素%胰島素牴抗%糖脂代謝
리랍로태%RNA간우%지련소%이도소저항%당지대사
Liraglutide%RNA interfering%Adiponectin%Insulin resistance%Glucose-lipid metabolism
目的 探讨利拉鲁肽对脂联素基因表达缺陷的ApoE基因敲除(ApoE-/-)小鼠糖脂代谢的影响.方法 采用静脉葡萄糖耐量试验(IVGTT)评价利拉鲁肽的量效关系.利用扩展高胰岛素钳夹技术评价各组小鼠糖脂代谢和胰岛素敏感性变化.结果 在IVGTT中,利拉鲁肽1 mg/kg组,糖负荷后5、15和30 min血糖值均明显低于其它剂量组(均P<0.01),而血浆胰岛素水平在5、15 min均明显高于其他3组(均P<0.01).联合注射利拉鲁肽和脂联素RNAi腺病毒组体重、空腹血糖、血浆游离脂肪酸、总胆固醇、甘油三酯、血浆胰岛素和低密度脂蛋白胆固醇(LDL-C)水平显著低于脂联素RNAi腺病毒组(P<0.05或P<0.01),而高密度脂蛋白胆固醇(HDL-C)则明显高于脂联素RNAi组(P<0.05).钳夹稳态时,脂联素RNAi组血浆胰岛素明显高于利拉鲁肽组(P<0.01),游离脂肪酸、总胆固醇、甘油三酯虽被抑制,但仍明显高于利拉鲁肽组(P<0.05).利拉鲁肽组葡萄糖输注率(GIR)则明显高于脂联素RNAi组(P<0.01).钳夹结束时,脂联素RNAi组葡萄糖清除率(GRd)明显低于利拉鲁肽组(P<0.01),而肝糖输出率则明显高于利拉鲁肽组(P<0.01).结论 长期的利拉鲁肽干预上调了脂联素基因表达缺陷ApoE-/-小鼠血浆脂联素水平,并改善了其胰岛素抵抗.
目的 探討利拉魯肽對脂聯素基因錶達缺陷的ApoE基因敲除(ApoE-/-)小鼠糖脂代謝的影響.方法 採用靜脈葡萄糖耐量試驗(IVGTT)評價利拉魯肽的量效關繫.利用擴展高胰島素鉗夾技術評價各組小鼠糖脂代謝和胰島素敏感性變化.結果 在IVGTT中,利拉魯肽1 mg/kg組,糖負荷後5、15和30 min血糖值均明顯低于其它劑量組(均P<0.01),而血漿胰島素水平在5、15 min均明顯高于其他3組(均P<0.01).聯閤註射利拉魯肽和脂聯素RNAi腺病毒組體重、空腹血糖、血漿遊離脂肪痠、總膽固醇、甘油三酯、血漿胰島素和低密度脂蛋白膽固醇(LDL-C)水平顯著低于脂聯素RNAi腺病毒組(P<0.05或P<0.01),而高密度脂蛋白膽固醇(HDL-C)則明顯高于脂聯素RNAi組(P<0.05).鉗夾穩態時,脂聯素RNAi組血漿胰島素明顯高于利拉魯肽組(P<0.01),遊離脂肪痠、總膽固醇、甘油三酯雖被抑製,但仍明顯高于利拉魯肽組(P<0.05).利拉魯肽組葡萄糖輸註率(GIR)則明顯高于脂聯素RNAi組(P<0.01).鉗夾結束時,脂聯素RNAi組葡萄糖清除率(GRd)明顯低于利拉魯肽組(P<0.01),而肝糖輸齣率則明顯高于利拉魯肽組(P<0.01).結論 長期的利拉魯肽榦預上調瞭脂聯素基因錶達缺陷ApoE-/-小鼠血漿脂聯素水平,併改善瞭其胰島素牴抗.
목적 탐토리랍로태대지련소기인표체결함적ApoE기인고제(ApoE-/-)소서당지대사적영향.방법 채용정맥포도당내량시험(IVGTT)평개리랍로태적량효관계.이용확전고이도소겸협기술평개각조소서당지대사화이도소민감성변화.결과 재IVGTT중,리랍로태1 mg/kg조,당부하후5、15화30 min혈당치균명현저우기타제량조(균P<0.01),이혈장이도소수평재5、15 min균명현고우기타3조(균P<0.01).연합주사리랍로태화지련소RNAi선병독조체중、공복혈당、혈장유리지방산、총담고순、감유삼지、혈장이도소화저밀도지단백담고순(LDL-C)수평현저저우지련소RNAi선병독조(P<0.05혹P<0.01),이고밀도지단백담고순(HDL-C)칙명현고우지련소RNAi조(P<0.05).겸협은태시,지련소RNAi조혈장이도소명현고우리랍로태조(P<0.01),유리지방산、총담고순、감유삼지수피억제,단잉명현고우리랍로태조(P<0.05).리랍로태조포도당수주솔(GIR)칙명현고우지련소RNAi조(P<0.01).겸협결속시,지련소RNAi조포도당청제솔(GRd)명현저우리랍로태조(P<0.01),이간당수출솔칙명현고우리랍로태조(P<0.01).결론 장기적리랍로태간예상조료지련소기인표체결함ApoE-/-소서혈장지련소수평,병개선료기이도소저항.
Objective To investigate the effects of liraglutide on glucose-lipid metabolism in ApoE-/-mice with RNAi-mediated adiponectin gene inhibition. Methods The dose-effective relationship of liraglutide was evaluated by intravenous glucose tolerance test (IVGTT), and the insulin sensitivity and glucose-lipid metabolism were assessed by the hyperinsulinemic-euglycemic clamp technique using 3-[3 H]-glucose as a tracer. Results In the IVGTT, blood glucose was significantly lower in the 1 mg/kg liraglutide group than that in other groups ( all P<0. 01 ) at the points of 5, 15, and 30 min after glucose load. However, plasma insulin was significantly higher at the points of 5 and 15 min (all P<0. 01 ). Fasting blood glucose (FBG), body weight, free fatty acids (FFA),total cholesterol, triglycerides, low-density lipoprotein-cholesterol ( LDL-C), and fasting plasma insulin in ApoE-/-mice with co-injection of liraglutide and adiponectin shRNA adenovirus ( HEA group ) were significantly lower than those in ApoE-/-mice with adiponectin shRNA adenovirus injection ( ADI group, P<0. 05 or P<0. 01 ). However,high-density lipoprotein-cholesterol (HDL-C) was significantly higher than the latter (P<0. 05 ). During the steady-state of clamp, plasma insulin in ADI group was significantly higher than that in HEA group (P<0. 01 ). Although FFA, total cholesterol, and triglycerides were suppressed in all groups, they were still higher in ADI group than those in HEA group (P<0. 05). Glucose infusion rate (GIR) in HEA group were significantly higher than that in ADI group ( P < 0. 01 ). At the end of clamp, glucose disappearance rate ( GRd ) was significantly lower, and hepatic glucose production significantly higher in ADI group than those in HEA group (P<0.01 ). Conclusion Administration of liraglutide may ameliorate insulin resistance via increasing plasma adiponectin level in ApoE-/-mice with RNAi-mediated adiponectin gene inhibition.