利拉鲁肽对糖尿病前期小鼠胰岛功能及胰岛微血管内皮细胞作用的研究
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摘要
目的探讨利拉鲁肽对糖尿病前期小鼠胰岛功能及胰岛微血管内皮细胞的作用。方法将30只雄性C57BL/6J小鼠随机分为正常饮食(Con)组、高脂饮食(HF)组、高脂饮食+利拉鲁肽干预组(LH),每组各10只,比较各组FBG、FIns、胰岛内胰岛素、CD31、血管内皮生长因子A(VEGF-A)蛋白表达及一氧化氮合酶(iNOS)、白细胞介素1β(IL-1β)mRNA表达量。结果各组FBG比较,差异无统计学意义(P>0.05)。LH组胰岛内胰岛素水平高于HF组(P<0.05),CD31蛋白表达[(0.196±0.002)vs(0.245±0.004)]及VEGF-A[(0.265±0.003)vs(0.413±0.005)]、IL-1β[(1.13±0.03)vs(1.54±0.02)]及iNOS[(1.28±0.02)vs(1.65±0.03)]mRNA表达均低于HF组(P<0.05)。结论利拉鲁肽可改善糖尿病前期小鼠胰岛功能,对胰岛微血管内皮细胞起保护作用。
Objective To explore the effect of Liraglutide on islet function and islet microvascular endothelial cells in mice with pre-diabetes. Methods Thirty male C57 BL/6 Jmice were randomly divided into three groups:control group(Con,n=10),high-fat dietgroup(HF,n=10)and high-fat diet plus Liraglutide group(LH,n=10).The FBG,FIns,the expression of insulin,CD31,VEGF-A,mRNA of iNOS and IL-1βin islet were detected. Results There was no significant difference in FBG among the three groups(P>0.05).The concentration of insulin in the islets was higher[(0.217±0.002)vs(0.195±0.002)ng/ml,P<0.05],the levels of CD31[(0.196±0.002)vs(0.245±0.004)],VEGF-A[(0.265±0.003)vs(0.413±0.005)],IL-1β[(1.13±0.03)vs(1.54±0.02)],and iNOS[(1.28±0.02)vs(1.65±0.03)]were lower in LH group than in HF group. Conclusion Liraglutide can improve pancreatic islet function and protect islet microvascular endothelial cells in mice with pre-diabetes.
Objective To explore the effect of Liraglutide on islet function and islet microvascular endothelial cells in mice with pre-diabetes. Methods Thirty male C57 BL/6 Jmice were randomly divided into three groups:control group(Con,n=10),high-fat dietgroup(HF,n=10)and high-fat diet plus Liraglutide group(LH,n=10).The FBG,FIns,the expression of insulin,CD31,VEGF-A,mRNA of iNOS and IL-1βin islet were detected. Results There was no significant difference in FBG among the three groups(P>0.05).The concentration of insulin in the islets was higher[(0.217±0.002)vs(0.195±0.002)ng/ml,P<0.05],the levels of CD31[(0.196±0.002)vs(0.245±0.004)],VEGF-A[(0.265±0.003)vs(0.413±0.005)],IL-1β[(1.13±0.03)vs(1.54±0.02)],and iNOS[(1.28±0.02)vs(1.65±0.03)]were lower in LH group than in HF group. Conclusion Liraglutide can improve pancreatic islet function and protect islet microvascular endothelial cells in mice with pre-diabetes.
引文
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[11]Gong L,Liu FQ,Wang J,et al.Hyperglycemia induces apoptosis of pancreatic islet endothelial cells via reactive nitrogen species-mediated Jun N-terminal kinase activation.Biochim Biophys Acta,2011,1813:1211-1219.
[2]Yuan L,Wang Y,Lu C,et al.Angiotensin-converting enzyme 2deficiency aggravates glucose into lerance via impairment of islet microvascular density in mice with high-fat diet.J Diabetes Res,2013,2013:405284.
[3]Chen C,Chmelova H,Cohrs CM,et al.Alterations in beta-cell calcium dynamics and efficacy outweigh islet mass adaptation in compensation of insulin resistance and prediabetes onset.Diabetes,2016,65:2676-2685.
[4]Carvalho CP,Oliveira RB,Britan A,et al.Impaired beta-cellbeta-cell coupling mediated by Cx36gap junctions in prediabetic mice.Am J Physiol Endocrinol Metab,2012,303:E144-E151.
[5]Nauck M.Incretin therapies:highlighting common features and differences in the modes of action of glucagon-like peptide-1receptor agonists and dipeptidyl peptidase-4inhibitors.Diabetes Obes Metab,2016,18:203-216.
[6]Bae EJ.DPP-4inhibitors in diabetic complications:role of DPP-4beyond glucose control.Arch Pharm Res,2016,39:1114-1128.
[7]Kostromina E,Gustavsson N,Wang X,et al.Glucose intolerance and impaired insulin secretion in pancreas-specific signal transducer and activator of transcription-3knockout mice are associated with microvascular alterations in the pancreas.Endocrinology,2010,151:2050-2059.
[8]Brissova M,Shostak A,Shiota M,et al.Pancreatic islet production of vascular endothelial growth factor--a is essential for islet vascularization,revascularization,and function.Diabetes,2006,55:2974-2985.
[9]Wei R,Ma S,Wang C,et al.Exenatide exerts direct protective effects on endothelial cells through the AMPK/Akt/eNOS pathway in a GLP-1receptor-dependent manner.Am J Physiol Endocrinol Metab,2016,310:E947-E957.
[10]Favaro E,Granata R,Miceli I,et al.The ghrelin gene products and exendin-4promote survival of human pancreatic islet endothelial cells in hyperglycaemic conditions,through phosphoinositide 3-kinase/Akt,extracellular signal-related kinase(ERK)1/2 and cAMP/protein kinase A(PKA)signalling pathways.Diabetologia,2012,55:1058-1070.
[11]Gong L,Liu FQ,Wang J,et al.Hyperglycemia induces apoptosis of pancreatic islet endothelial cells via reactive nitrogen species-mediated Jun N-terminal kinase activation.Biochim Biophys Acta,2011,1813:1211-1219.