Please wait a minute...
文章检索
预防医学  2021, Vol. 33 Issue (11): 1122-1125,1129    DOI: 10.19485/j.cnki.issn2096-5087.2021.11.010
  综述 本期目录 | 过刊浏览 | 高级检索 |
胰岛素抵抗及高胰岛素血症促进胰腺癌发生的研究进展
李珊珊 综述, 赵钰岚 审校
浙江大学医学院附属第一医院胰腺病研究重点实验室,浙江 杭州 310003
Research progress of insulin resistance and hyperinsulinemia promoting pancreatic cancer
LI Shanshan, ZHAO Yulan
Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital to School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China
全文: PDF(848 KB)  
输出: BibTeX | EndNote (RIS)      
摘要 胰腺癌是常见的消化道恶性肿瘤,因其隐匿性强且缺乏早期诊断指标,患者生存率极低。胰腺癌的发病机制尚不明确,吸烟、家族史、糖尿病和肥胖可能与其发生相关,其中2型糖尿病(T2DM)和胰腺癌常合并发生。胰岛素抵抗及代偿性高胰岛素血症是T2DM的主要代谢特征,在胰腺癌的发生发展过程中可能起重要促进作用。本文就胰岛素抵抗及高胰岛素血症促进胰腺癌发生的分子机制进行综述,为胰腺癌防治供依据。
服务
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章
李珊珊
赵钰岚
关键词 胰腺癌胰岛素抵抗高胰岛素血症2型糖尿病    
Abstract:Pancreatic cancer is a common digestive tract carcinoma. It is strongly occult and lack of early diagnostic indicators, and the patients have quite low survival rates. The pathogenesis of pancreatic cancer remains unclear. It has been reported that smoking, family history, diabetes mellitus and obesity are associated with the incidence of pancreatic cancer; moreover, type 2 diabetes mellitus (T2DM) often occur as a comorbidity. Insulin resistance and compensatory hyperinsulinemia are the main metabolic characteristics of T2DM, which play an important role in the development and progression of pancreatic cancer. The molecular mechanisms of insulin resistance and hyperinsulinemia promoting pancreatic cancer are reviewed in this paper, in order to provide the evidence for the prevention and treatment of pancreatic cancer.
Key wordspancreatic cancer    insulin resistance    hyperinsulinemia    type 2 diabetes mellitus
收稿日期: 2021-05-07      修回日期: 2021-07-15      出版日期: 2021-11-10
中图分类号:  R735.9  
通信作者: 赵钰岚,E-mail:yulan_zhao@zju.edu.cn   
作者简介: 李珊珊,硕士,助理实验师,主要从事胰腺癌发病机制研究工作
引用本文:   
李珊珊, 赵钰岚. 胰岛素抵抗及高胰岛素血症促进胰腺癌发生的研究进展[J]. 预防医学, 2021, 33(11): 1122-1125,1129.
LI Shanshan, ZHAO Yulan. Research progress of insulin resistance and hyperinsulinemia promoting pancreatic cancer. Preventive Medicine, 2021, 33(11): 1122-1125,1129.
链接本文:  
http://www.zjyfyxzz.com/CN/10.19485/j.cnki.issn2096-5087.2021.11.010      或      http://www.zjyfyxzz.com/CN/Y2021/V33/I11/1122
[1] POTHURAJU R,RACHAGANI S,JUNKER W M,et al.Pancreatic cancer associated with obesity and diabetes:an alternative approach for its targeting[J/OL].J Exp Clin Cancer Res,2018,37(2018-12-19)[2021-07-15].https://jeccr.biomedcentral.com/articles/10.1186/s13046-018-0963-4.
[2] TEMPERO M A.NCCN guidelines updates:pancreatic cancer[J].J Natl Compr Canc Netw,2019,17(5.5):603-605.
[3] VINCENT A,HERMAN J,SCHULICK R,et al.Pancreatic cancer[J].Lancet,2011,378(9791):607-620.
[4] HUANG B Z,CHANG J I,LI E,et al.Influence of statins and cholesterol on mortality among patients with pancreatic cancer[J/OL].J Natl Cancer Inst,2016,109(5)(2016-12-31)[2021-07-15].https://academic.oup.com/jnci/article/109/5/djw275/2898139.DOI:10.1093/jnci/djw275.
[5] ILIC M,ILIC I.Epidemiology of pancreatic cancer[J].World J Gastroenterol,2016,22(44):9694-9705.
[6] KIM N H,CHANG Y,LEE S R,et al.Glycemic status,insulin resistance,and risk of pancreatic cancer mortality in individuals with and without diabetes[J].Am J Gastroenterol,2020,115(11):1840-1848.
[7] ANDERSEN D K.Diabetes and cancer:placing the association in perspective[J].Curr Opin Endocrinol Diabetes Obes,2013,209(2):81-86.
[8] MAKHOUL I,YACOUB A,SIEGEL E.Type 2 diabetes mellitus is associated with increased risk of pancreatic cancer:a veteran administration registry study[J/OL].SAGE Open Med,2016,4(2016-12-14)[2021-07-15].https://journals.sagepub.com/doi/10.1177/2050312116682257?url_ver=Z39.88-2003&rfr_id=o.
[9] MUTGAN A C,BESIKCIOGLU H E,WANG S,et al.Insulin/IGF-driven cancer cell-stroma crosstalk as a novel therapeutic target in pancreatic cancer[J/OL].Mol Cancer,2018,17(1)(2018-02-23)[2021-07-15].https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-018-0806-0.
[10] LI D,YEUNG S J,HASSAN M M,et al.Antidiabetic therapies affect risk of pancreatic cancer[J].Gastroenterology,2009,137(2):482-488.
[11] BAO Y,NIMPTSCH K,WOLPIN B M,et al.Dietary insulin load,dietary insulin index,and risk of pancreatic cancer[J].Am J Clin Nutr,2011,94(3):862-868.
[12] ROBERT C T,MATTIAS J,VALERIE G,et al.The role of obesity,type 2 diabetes,and metabolic factors in pancreatic cancer:a Mendelian randomization study[J/OL].J Natl Cancer Inst,2017,109(9)(2018-04-28)[2021-07-15].https://academic.oup.com/jnci/article/109/9/djx012/3778207.
[13] POLVANI S,TAROCCHI M,TEMPESTI S,et al.Peroxisome proliferator activated receptors at the crossroad of obesity,diabetes,and pancreatic cancer[J].World J Gastroenterol,2016,22(8):2441-2459.
[14] ZHANG A,MAGRILL J,WINTER T,et al.Endogenous hyperinsulinemia contributes to pancreatic cancer development[J].Cell Metab,2019,30(3):403-404.
[15] CUI Y F,ANDERSEN D K.Diabetes and pancreatic cancer[J].Endocr Relat Cancer,2012,19(5):F9-F26.
[16] TRAJKOVIC-ARSIC M,KALIDERIS E,SIVEKE J T.The role of insulin and IGF system in pancreatic cancer[J].J Mol Endocrinol,2013,50(3):R67-R74.
[17] VALSECCHI M E,MCDONALD M,BRODY J R,et al.Epidermal growth factor receptor and insulin like growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma[J].Cancer,2012,118(14):3484-3493.
[18] SIDDLE K.Signalling by insulin and IGF receptors:supporting acts and new players[J].J Mol Endocrinol,2011,47(1):R1-R10.
[19] APPLEMAN V A,AHRONIAN L G,CAI J,et al.KRASG12D-and BRAFV600E-induced transformation of murine pancreatic epithelial cells requires MEK/ERK-stimulated IGF1R signaling[J].Mol Cancer Res,2012,10(9):1228-1239.
[20] EIBL G,CRUZ-MONSERRATE Z,KORC M,et al.Diabetes mellitus and obesity as risk factors for pancreatic cancer[J].J Acad Nutr Diet,2018,118(4):555-567.
[21] OMARY M B,LUGEA A,LOWE A W,et al.The pancreatic stellate cell:a star on the rise in pancreatic diseases[J].J Clin Invest,2007,117(1):50-59.
[22] DAWSON D W,HERTZER K,MORO A,et al.High-fat,high-calorie diet promotes early pancreatic neoplasia in the conditional KrasG12D mouse model[J].Cancer Prev Res(Phila),2013,6(10):1064-1073.
[23] MOHAPATRA S,MAJUMDER S,SMYRK T C,et al.Diabetes mellitus is associated with an exocrine pancreatopathy:conclusions from a review of literature[J].Pancreas,2016,45(8):1104-1110.
[24] BIOCHEM A R.Fat and beyond:the diverse biology of PPARγ[J].Annu Rev Biochem,2008,77(1):289-312.
[25] GUPTA D,JETTON T L,MORTENSEN R M,et al.In vivo and in vivo studies of a functional peroxisome proliferator-activated receptor gamma response element in the mouse pdx-1 promoter[J].J Biol Chem,2008,283(47):32462-32470.
[26] GUPTA D,KONO T,EVANS-MOLINA C.The role of peroxisome proliferator activated receptor γ in pancreatic β cell function and survival:therapeutic implications for the treatment of type 2 diabetes mellitus[J].Diabetes Obes Metab,2010,12(12):1036-1047.
[27] POLVANI S,TAROCCHI M,TEMPESTI S,et al.Nuclear receptors and pathogenesis of pancreatic cancer[J].World J Gastroenterol,2014,20(34):12062-12081.
[28] KOGA H,SELVENDIRAN K,SIVAKUMAR R,et al.PPARγ potentiates anticancer effects of gemcitabine on human pancreatic cancer cells[J].Int J Oncol,2012,40(3):679-685.
[29] RIUS-PÉREZ S,TORRES-CUEVAS I,MILLÁN I,et al.PGC-1α,inflammation,and oxidative stress:an integrative view in metabolism[J/OL].Oxid Med Cell Longev,2020(2020-03-09)[2021-07-15].https://www.hindawi.com/journals/omcl/2020/1452696.DOI:10.1155/2020/1452696.
[30] HOTAMISLIGIL G S,BUDAVARI A,MURRAY D L,et al.Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes.Central role of tumor necrosis factor-alpha[J].J Clin Invest,1994,94(4):1543-1549.
[31] ALJADA A,GHANIM H,ASSIAN E,et al.Tumor necrosis factor-alpha inhibits insulin-induced increase in endothelial nitric oxide synthase and reduces insulin receptor content and phosphorylation in human aortic endothelial cells[J].Metabolism,2002,51(4):487-491.
[32] GUILHERME A,VIRBASIUS J V,PURI V,et al.Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes[J].Nat Rev Mol Cell Biol,2008,9(5):367-377.
[33] HOTAMISLIGIL G S.Inflammation,metaflammation and immunometabolic disorders[J].Nature,2017,542(7640):177-185.
[34] SOLINAS G,BECATTINI B.JNK at the crossroad of obesity,insulin resistance,and cell stress response[J].Mol Metab,2016,6(2):174-184.
[35] ZHONG Y,NAITO Y,COPE L,et al.Functional p38 MAPK identified by biomarker profiling of pancreatic cancer restrains growth through JNK inhibition and correlates with improved survival[J].Clin Cancer Res,2014,20(23):6200-6211.
[36] LIU M Y,ZHANG Y Q,YANG J X,et al.ZIP4 increases expression of transcription factor ZEB1 to promote integrin α3β1 signaling and inhibit expression of the gemcitabine transporter ENT1 in pancreatic cancer cells[J].Gastroenterology,2020,158(3):679-692.
[37] HAMARSHEH S,GROβ O,BRUMMER T,et al.Immune modulatory effects of oncogenic KRAS in cancer[J/OL].Nat Commun,2020,11(1)(2020-11-28)[2021-07-15].https://www.nature.com/articles/s41467-020-19288-6.DOI:10.1038/s41467-020-19288-6.
[38] PADOAN A,PLEBANI M,BASSO D.Inflammation and pancreatic cancer:focus on metabolism,cytokines,and immunity[J/OL].Int J Mol Sci,2019,20(3):676(2019-09-05)[2021-07-15].https://www.mdpi.com/1422-0067/20/3/676.DOI:10.3390/ijms20030676.
[39] SENN J J,KLOVER P J,NOWAK I A,et al.Interleukin-6 induces cellular insulin resistance in hepatocytes[J].Diabetes,2002,51(12):3391-3399.
[1] 柏旭, 苏洁, 李凤, 徐倩, 沈源, 肖凌凤. 我国成人糖尿病视网膜病变影响因素的Meta分析[J]. 预防医学, 2023, 35(7): 595-601.
[2] 沈放如, 杨可, 刘厚璞, 朱家豪, 李迎君. 新生儿出生体重与母亲2型糖尿病关联的双向孟德尔随机化研究[J]. 预防医学, 2023, 35(5): 384-387,409.
[3] 刘国志, 袁空军, 庄蔚, 周光清. 国内外城市社区2型糖尿病健康管理模式比较[J]. 预防医学, 2023, 35(3): 262-266.
[4] 汤洋, 李琳, 廖兴, 林坚. 2型糖尿病患者体感运动联合神经肌肉穴位电刺激干预效果评价[J]. 预防医学, 2022, 34(8): 794-798.
[5] 孙霞, 朱艳, 郑鹏, 徐爱花, 董海娜. 超重肥胖和2型糖尿病对瘦素、内脂素的影响研究[J]. 预防医学, 2022, 34(6): 581-585.
[6] 何雅薇, 葛华英, 李修英, 叶赵芳, 孔利萍. 中青年2型糖尿病患者自我管理行为的影响因素研究[J]. 预防医学, 2022, 34(3): 258-262.
[7] 周晓燕, 胡如英, 何青芳, 潘劲, 龚巍巍, 陆凤, 王蒙, 钟节鸣. 浙江省农村2型糖尿病患者糖化血红蛋白控制水平及影响因素分析[J]. 预防医学, 2022, 34(2): 123-128.
[8] 王临池, 黄春妍, 华钰洁, 吴学飞, 陆艳. 2006—2020年苏州市胰腺癌死亡及减寿分析[J]. 预防医学, 2022, 34(2): 185-189.
[9] 苏银霞, 卢耀勤, 田翔华, 李莉, 姚华. 基于常规体检指标的2型糖尿病风险预测研究进展[J]. 预防医学, 2022, 34(12): 1230-1234.
[10] 贾庆梅, 张丽, 喻喆, 陈为霞, 孔利萍. 青年2型糖尿病患者糖尿病痛苦水平及其影响因素分析[J]. 预防医学, 2021, 33(8): 808-811.
[11] 杨晓迪, 李曾荣, 刘素贞. 中青年2型糖尿病患者心理弹性的影响因素分析[J]. 预防医学, 2021, 33(7): 665-669.
[12] 孙惠昕, 张茂祥, 贾海晗, 王婉莹, 宋冰冰. 2013—2017年黑龙江省居民胰腺癌发病和死亡趋势[J]. 预防医学, 2021, 33(6): 599-601,606.
[13] 李文丽, 苏银霞, 诸葛瑾慧, 王育珊, 王淑霞, 姚华. 新源县哈萨克族人群主要慢性病的影响因素分析[J]. 预防医学, 2021, 33(4): 398-403.
[14] 潘冬梅, 王佳蓓, 郭庆, 李静静. 老年2型糖尿病患者合并骨质疏松症的影响因素分析[J]. 预防医学, 2021, 33(4): 382-384,387.
[15] 唐英琪, 李英, 田坚. 2型糖尿病患者合并非酒精性脂肪性肝病的影响因素分析[J]. 预防医学, 2021, 33(3): 292-294.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed