[1]辛丽娟a,宁建峰b,唐宏霞a,等.贝那鲁肽对高糖诱导的胰岛 β细胞功能障碍和凋亡的影响及机制研究[J].现代检验医学杂志,2022,37(01):103-106.[doi:10.3969/j.issn.1671-7414.2022.01.021]
　XIN Li-juana,NING Jian-fengb,TANG Hong-xiaa,et al.Effect and Mechanism of Beinaglutide on Islet β Cell Dysfunction and Apoptosis Induced by High Glucose[J].Journal of Modern Laboratory Medicine,2022,37(01):103-106.[doi:10.3969/j.issn.1671-7414.2022.01.021]
点击复制

贝那鲁肽对高糖诱导的胰岛 β细胞功能障碍和凋亡的影响及机制研究()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第37卷
期数:
2022年01期
页码:
103-106
栏目:
论　著
出版日期:
2022-01-15

文章信息/Info

Title:
Effect and Mechanism of Beinaglutide on Islet β Cell Dysfunction and Apoptosis Induced by High Glucose
文章编号:
1671-7414（2022）01-103-05
作者:
辛丽娟a; 宁建峰b; 唐宏霞a; 左源渊a; 王新婷a; 彭　一c; 尚宏博d; 鲍喜静d
（张家口市第一医院a. 内分泌二科；b. 检验科；c. 内分泌代谢病门诊；d. 内分泌一科，河北张家口，075000）
Author(s):
XIN Li-juana;  NING Jian-fengb;  TANG Hong-xiaa;  ZUO Yuan-yuana;  WANG Xin-tinga; PENG Yic;  SHANG Hong-bod;  BAO Xi-jingd
（a. Department of Endocrinology II ; b. Department of Clinical Laboratory; c. Endocrine and Metabolic Diseases Clinic;d.Department of Endocrinology I, the First Hospital of Zhangjiakou, Hebei Zhangjiakou 075000, China）
关键词:
贝那鲁肽; INS-1胰岛β细胞;  NF-κB; 巨噬细胞迁移抑制因子; 凋亡
分类号:
R587；R446
DOI:
10.3969/j.issn.1671-7414.2022.01.021
文献标志码:
A
摘要:
目的　探讨贝那鲁肽对高糖诱导的胰岛 β细胞功能障碍和凋亡的影响以及相关机制。方法　将 INS-1胰岛 β细胞随机分为对照组、高糖组、贝那鲁肽处理组、 MG-132预处理组和 ISO-1预处理组，对照组给予 5.5mmol/L葡萄糖处理，高糖组给予 30 mmol/L葡萄糖处理，贝那鲁肽处理组在高糖组的基础上给予 1 nmol/L贝那鲁肽处理， MG-132预处理组和 ISO-1预处理组分别在高糖的基础上给予 20 μmol/L MG-132和 50 μmol/L ISO-1预处理。培养 24h后噻唑蓝（ MTT）比色法评估细胞的活力，酶联免疫吸附法（ ELISA）检测 INS-1胰岛 β细胞胰岛素和巨噬细胞迁移抑制因子（ MIF）的分泌， Western blot检测凋亡相关蛋白（ Bax和 cleaved caspase 3）和 NF-κB通路相关蛋白（ p-IκB，IκB和 NF-κBp65）的表达。结果　与对照组相比，高糖组胰岛 β细胞的存活率（ t=4.949，P＜ 0.01）、胰岛素的分泌（ t=3.168, 4.273，均 P＜ 0.05）和 IκB的表达（ t=3.062，P＜ 0.05）明显降低，凋亡相关蛋白（ Bax和 cleaved caspase 3）的表达（ t=2.923, 3.141，均 P＜ 0.05）、p-IκB和 NF-κB p65表达（ t=3.544, 4.658，均 P＜ 0.01）以及 MIF分泌（ t=3.024，P＜ 0.05）明显增加 .与高糖组相比，贝那鲁肽处理组可逆转高糖组上述指标的变化（ t=2.415 ~ 4.290，均 P＜ 0.05），差异均有统计学意义。进一步给予 NF-κB抑制剂 MG-132和 MIF抑制剂 ISO-1预处理后，与高糖组相比， MG-132预处理组和 ISO-1预处理组均可改善高糖诱导的 INS-1胰岛 β细胞胰岛素分泌功能（ t=2.515 ~ 6.867，均 P＜ 0.05），还可降低凋亡相关蛋白 Bax（t=4.022,
Abstract:
Objective　To investigate the effects and mechanisms of benaglutide onhigh glucose-induced islet β cell dysfunctionand apoptosis. Methods　INS-1 islet β cells were randomly divided into control group, high glucose group, benaglutidetreatment group, MG-132 pretreatment group and ISO-1 pretreatment group. The control group was administered 5.5 mmol/Lglucose, the high glucose group was administered 30 mmol/L glucose, and the benaglutide treatment group was administered 1nmol/L benaglutide on the basis of the high glucose group, the MG-132 pretreatment group and ISO-1 pretreatment group wereadministered 20 μmol/L MG-132 and 50 μmol/L ISO-1 on the basis of high glucose group. The cells viability, the levels ofinsulin and macrophage migration inhibitory factor (MIF), and the expression of apoptosis-related proteins (Bax and clearedcaspase 3) and NF-κB pathway-related proteins (p-IκB, IκB and NF-κB p65) in INS-1 islet β cells were respectivelyevaluated by the MTT assay, enzyme-linked immunosorbent assay (ELISA), and Western blot after 24 hours of culture. Results　Comparedwith the control group, the cells viability (t=4.949, P<0.01), insulin secretion (t=3.168, 4.273, all P <0.05), and IκB expression(t=3.062, P<0.05) of islet β cells in the high glucose group were significantly reduced, apoptosis-related proteins (Bax andcleared caspase 3) (t=2.923, 3.141, all P <0.05)， p-IκB (t=3.544, P<0.01) and NF-κB p65 (t=4.658, P<0.01) expressionand MIF secretion (t=3.024, P <0.05) were significantly increased. Compared with the high glucose group, the changes of aboveindicators were reversed in benaglutide treatment group (t=2.415 ~ 4.290, all P<0.05), the differences were statistically significantrespectively. Furthermore, compared with the high glucose group, the MG-132 pretreatment group and the ISO-1 pretreatmentgroup couldimprove the high glucose-induced INS-1 Insulin β cells insulin secretion function (t=2.515 ~ 6.867, all P <0.05),andreduce apoptosis-related proteins Bax (t=4.022, 2.554, all P <0.05) and cleared caspase 3 (t=4.022 2.760 , all P <0.05)expression, the differences were statistically significant. Conclusion　Benaglutide can alleviate high glucose-induced islet βcells dysfunction and apoptosis by inhibiting the NF-κB / MIF-dependent inflammatory pathway.

参考文献/References:

[1] ZHENG Yan, LEY S H, HU F B. Global aetiologyand epidemiology of type 2 diabetes mellitus and itscomplications[J]. Nature Reviews Endocrinology, 2018,14(2): 88-98.
[2] ZHENG S L, RODDICK A J, AGHAR-JAFFAR R,et al. Association between use of sodium-glucosecotransporter 2 inhibitors, glucagon-like peptide 1agonists, and dipeptidyl peptidase 4 inhibitors withall-cause mortality in patients with type 2 diabetes: asystematic review and meta-analysis[J]. JAMA, 2018,319(15) : 1580-1591.
[3] AGUAYO-MAZZUCATO C, BONNER-WEIR S.Pancreatic β cell regeneration as a possible therapy fordiabetes[J]. Cell Metabolism, 2018, 27(1): 57-67.
[4] BENTHUYSEN J R, CARRANO A C, SANDER M.Advances in β cell replacement and regenerationstrategies for treating diabetes[J].The Journal ofClinical Investigation, 2016, 126(10): 3651-3660.
[5] LEE Y S, JUN H S. Anti-inflammatory effects of GLP-1-based therapies beyond glucose control[J]. Mediatorsof Inflammation, 2016,2016: 3094642.
[6] LIAO Pengzhi, YANG Dan, LIU Duan, et al. GLP-1and ghrelin attenuate high glucose/high lipid-inducedapoptosis and senescence of human microvascular endothelialcells[J].Cellular Physiology and Biochemistry,2017, 44(5) : 1842-1855.
[7] KAPODISTRIA K, TSILIBARY E P, KOTSOPOULOUE, et al. Liraglutide, a human glucagon-like peptide-1analogue, stimulates AKT-dependent survival signallingand inhibits pancreatic β-cell apoptosis[J]. Journal ofCellular and Molecular Medicine, 2018, 22(6): 2970-2980.
[8] HANSCHMANN E M, PETRY S F, EITNER S, et al.Paracrine regulation and improvement of β-cell functionby thioredoxin[J]. Redox Biology, 2020, 34(7): 101570.
[9] MARGARYAN S, KRIEGOVA E, FILLEROVA R, etal. Hypomethylation of IL1RN and NFKB1 genes islinked to the dysbalance in IL1β/IL-1Ra axis in femalepatients with type 2 diabetes mellitus[J]. PLoS One,2020, 15(5): e0233737.
[10] LIANG Hongzhi, WANG Huajun, LUO Leifeng, etal. Toll-like receptor 4 promotes high glucose-inducedcatabolic and inflammatory responses in chondrocytesin an NF-κB-dependent manner[J]. Life Sciences,2019, 228(7): 258-265.
[11] BLOOM J, SUN S, AL-ABED Y. MIF, a controversialcytokine: a review of structural features, challenges, andopportunities for drug development[J]. Expert Opinion onTherapeutic Targets, 2016, 20(12): 1463-1475.
[12] CALANDRA T, BUCALA R. Macrophage migrationinhibitory factor (MIF): A glucocorticoid counterregulatorwithin the immune system[J]. CriticalReviews in Immunology, 2018, 37(2-6) : 381-391.
[13] KIM H K, GARCIA A B, SIU E, et al. Macrophagemigration inhibitory factor regulates innate γδ T-cellresponses via IL-17 expression[J]. FASEB Journal:2019, 33(6): 6919-6932.
[14] 胡红丽, 杨静文, 谷明莉, 等.MIF 在隐球菌脑膜炎患者外周血单个核细胞中升高及临床意义[J]. 现代检验医学杂志, 2017, 32(1):16-18.HU Hongli, YANG Jingwen, GU Mingli, et al.Increased expression of MIF in peripheral bloodmononuclear cells from patients with crytococcalmeningitis and its clinical significance [J]. Journal ofModern Laboratory Medicine, 2017, 32（1):16-18.
[15] ZHENG Shuang, REN Xingxing, HAN Tingting, et al.Fenofibrate attenuates fatty acid-induced islet β-celldysfunction and apoptosis via inhibiting the NF-κB/MIF dependent inflammatory pathway[J]. Metabolism-Clinical and Experimental, 2017, 77: 23-38.
[16] STO?I?-GRUJI?I? S, SAKSIDA T, MILJKOVI? ?,etal.MIF and insulin: Lifetime companions from commongenesis to common pathogenesis[J]. Cytokine, 2020,125(1): 154792.
[17] KAWAMORI D, SHIRAKAWA J, LIEW C W, et al.GLP-1 signalling compensates for impaired insulinsignalling in regulating beta cell proliferation inβIRKO mice[J].Diabetologia, 2017, 60(8): 1442-1453.
[18] M?LLER T D, FINAN B, BLOOM S R, et al. Glucagon-like peptide 1 (GLP-1)[J]. Molecular Metabolism,2019, 30(11): 72-130.
[19] MA Gefei, CHEN Song, YIN Lei, et al. Exendin-4ameliorates oxidized-LDL-induced inhibition ofmacrophage migration in vitro via the NF-κB pathway.[J]. Acta Pharmacologica Sinica, 2014, 35(2) : 195-202.

备注/Memo

备注/Memo:
基金课题：2019 年度张家口市科技计划项目（编号：1921081D）。
作者简介：辛丽娟（1984-），女，本科，主治医师，研究方向：内分泌临床代谢性疾病方向，E-mail：xinwin321@163.com。
通讯作者：宁建峰（1978-），男，本科，主管检验师，研究方向：临床医学检验诊断，E-mail：444256816@qq.com。
更新日期/Last Update: 1900-01-01