中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

胰源性糖尿病的发病机制探析

王晨晓 王晓 王希望 金晶晶 王莹 刘江凯 燕树勋

引用本文:
Citation:

胰源性糖尿病的发病机制探析

DOI: 10.12449/JCH240834
基金项目: 

国家中医临床研究基地科研专项 (2021JDZY034);

河南省中医药科学研究专项课题 (2022ZY1030)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:王晨晓、王希望负责文献检索,撰写论文;王莹、金晶晶参与收集数据,资料整理;刘江凯负责修改论文;燕树勋、王晓负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    燕树勋, ysx982001@163.com (ORCID: 0000-0003-0910-6314)

Pathogenesis of pancreatogenic diabetes

Research funding: 

National Traditional Chinese Medicine Clinical Research Base Scientific Research Project (2021JDZY034);

Special Project of Traditional Chinese Medicine Scientific Research in Henan Province (2022ZY1030)

More Information
    Corresponding author: YAN Shuxun, ysx982001@163.com (ORCID: 0000-0003-0910-6314)
  • 摘要: 胰源性糖尿病是一种继发于胰腺外分泌疾病的糖尿病,2014年被美国糖尿病学会正式命名,慢性胰腺炎和胰腺癌是其最主要的发病原因。该病的发病机制尚不完全明确,系统的治疗方案尚未形成,因此国内外关于胰源性糖尿病的误诊率极高,且研究发现该型糖尿病患者与2型糖尿病相比具有更高的死亡和再入院风险,这无疑对患者的健康和临床治疗充满挑战。因此充分了解、早期正确识别及诊断胰源性糖尿病,对降低该病的致残率与病死率具有重要意义。本文对胰源性糖尿病可能的发病机制进行阐述与分析。

     

  • 图  1  免疫机制引发胰腺纤维化示意图

    Figure  1.  Schematic diagram of immune mechanisms triggering pancreatic fibrosis

  • [1] MAKUC J. Management of pancreatogenic diabetes: Challenges and solutions[J]. Diabetes Metab Syndr Obes, 2016, 9: 311- 315. DOI: 10.2147/DMSO.S99701.
    [2] PETROV MS, BASINA M. Diagnosis of endocrine disease: Diagnosing and classifying diabetes in diseases of the exocrine pancreas[J]. Eur J Endocrinol, 2021, 184( 4): R151- R163. DOI: 10.1530/EJE-20-0974.
    [3] VONDERAU JS, DESAI CS. Type 3c: Understanding pancreatogenic diabetes[J]. JAAPA, 2022, 35( 11): 20- 24. DOI: 10.1097/01.JAA.0000885140.47709.6f.
    [4] CHO J, SCRAGG R, PETROV MS. Risk of mortality and hospitalization after post-pancreatitis diabetes mellitus vs type 2 diabetes mellitus: A population-based matched cohort study[J]. Am J Gastroenterol, 2019, 114( 5): 804- 812. DOI: 10.14309/ajg.0000000000000225.
    [5] SANTOS R, COLEMAN HG, CAIRNDUFF V, et al. Clinical prediction models for pancreatic cancer in general and at-risk populations: A systematic review[J]. Am J Gastroenterol, 2023, 118( 1): 26- 40. DOI: 10.14309/ajg.0000000000002022.
    [6] American Diabetes Association. 2. classification and diagnosis of diabetes: Standards of medical care in diabetes-2021[J]. Diabetes Care, 2021, 44( Suppl 1): S15- S33. DOI: 10.2337/dc21-S002.
    [7] LI GQ, SUN JF, ZHANG J, et al. Identification of inflammation-related biomarkers in diabetes of the exocrine pancreas with the use of weighted gene co-expression network analysis[J]. Front Endocrinol, 2022, 13: 839865. DOI: 10.3389/fendo.2022.839865.
    [8] POLLARD JW. The yolk sac feeds pancreatic tumors[J]. Immunity, 2017, 47( 2): 217- 218. DOI: 10.1016/j.immuni.2017.07.021.
    [9] ZHANG H, CAI D, BAI X. Macrophages regulate the progression of osteoarthritis[J]. Osteoarthritis Cartilage, 2020, 28( 5): 555- 561. DOI: 10.1016/j.joca.2020.01.007.
    [10] SWAIN SM, ROMAC JMJ, SHAHID RA, et al. TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation[J]. J Clin Invest, 2020, 130( 5): 2527- 2541. DOI: 10.1172/JCI134111.
    [11] PALLAGI P, MADÁCSY T, VARGA Á, et al. Intracellular Ca2+ signalling in the pathogenesis of acute pancreatitis: Recent advances and translational perspectives[J]. Int J Mol Sci, 2020, 21( 11): 4005. DOI: 10.3390/ijms21114005.
    [12] ZHANG Y, ZHANG WQ, LIU XY, et al. Immune cells and immune cell-targeted therapy in chronic pancreatitis[J]. Front Oncol, 2023, 13: 1151103. DOI: 10.3389/fonc.2023.1151103.
    [13] LIU SY, SZATMARY P, LIN JW, et al. Circulating monocytes in acute pancreatitis[J]. Front Immunol, 2022, 13: 1062849. DOI: 10.3389/fimmu.2022.1062849.
    [14] SALUJA A, DUDEJA V, DAWRA R, et al. Early intra-acinar events in pathogenesis of pancreatitis[J]. Gastroenterology, 2019, 156( 7): 1979- 1993. DOI: 10.1053/j.gastro.2019.01.268.
    [15] KRATOCHVILL F, NEALE G, HAVERKAMP JM, et al. TNF counterbalances the emergence of M2 tumor macrophages[J]. Cell Rep, 2015, 12( 11): 1902- 1914. DOI: 10.1016/j.celrep.2015.08.033.
    [16] PAVAN KUMAR P, RADHIKA G, RAO GV, et al. Interferon γ and glycemic status in diabetes associated with chronic pancreatitis[J]. Pancreatology, 2012, 12( 1): 65- 70. DOI: 10.1016/j.pan.2011.12.005.
    [17] CASU AN, GRIPPO PJ, WASSERFALL C, et al. Evaluating the immunopathogenesis of diabetes after acute pancreatitis in the diabetes RElated to acute pancreatitis and its mechanisms study: From the type 1 diabetes in acute pancreatitis consortium[J]. Pancreas, 2022, 51( 6): 580- 585. DOI: 10.1097/MPA.0000000000002076.
    [18] WEN L, JAVED TA, DOBBS AK, et al. The protective effects of calcineurin on pancreatitis in mice depend on the cellular source[J]. Gastroenterology, 2020, 159( 3): 1036- 1050. e 8. DOI: 10.1053/j.gastro.2020.05.051.
    [19] JAGANJAC M, CIPAK A, SCHAUR RJ, et al. Pathophysiology of neutrophil-mediated extracellular redox reactions[J]. Front Biosci(Landmark Ed), 2016, 21( 4): 839- 855. DOI: 10.2741/4423.
    [20] XIA D, HALDER B, GODOY C, et al. NADPH oxidase 1 mediates caerulein-induced pancreatic fibrosis in chronic pancreatitis[J]. Free Radic Biol Med, 2020, 147: 139- 149. DOI: 10.1016/j.freeradbiomed.2019.11.034.
    [21] CANNON A, THOMPSON CM, BHATIA R, et al. Molecular mechanisms of pancreatic myofibroblast activation in chronic pancreatitis and pancreatic ductal adenocarcinoma[J]. J Gastroenterol, 2021, 56( 8): 689- 703. DOI: 10.1007/s00535-021-01800-4.
    [22] SCHMITZ-WINNENTHAL H, PIETSCH DH, SCHIMMACK S, et al. Chronic pancreatitis is associated with disease-specific regulatory T-cell responses[J]. Gastroenterology, 2010, 138( 3): 1178- 1188. DOI: 10.1053/j.gastro.2009.11.011.
    [23] ZHOU Q, TAO XF, XIA SL, et al. T lymphocytes: A promising immunotherapeutic target for pancreatitis and pancreatic cancer?[J]. Front Oncol, 2020, 10: 382. DOI: 10.3389/fonc.2020.00382.
    [24] GLAUBITZ J, WILDEN A, GOLCHERT J, et al. In mouse chronic pancreatitis CD25+FOXP3+ regulatory T cells control pancreatic fibrosis by suppression of the type 2 immune response[J]. Nat Commun, 2022, 13( 1): 4502. DOI: 10.1038/s41467-022-32195-2.
    [25] CHANG M, CHEN WJ, XIA RT, et al. Pancreatic stellate cells and the targeted therapeutic strategies in chronic pancreatitis[J]. Molecules, 2023, 28( 14): 5586. DOI: 10.3390/molecules28145586.
    [26] RABIEE A, GALIATSATOS P, SALAS-CARRILLO R, et al. Pancreatic polypeptide administration enhances insulin sensitivity and reduces the insulin requirement of patients on insulin pump therapy[J]. J Diabetes Sci Technol, 2011, 5( 6): 1521- 1528. DOI: 10.1177/193229681100500629.
    [27] APTE M, PIROLA R, WILSON J. The fibrosis of chronic pancreatitis: New insights into the role of pancreatic stellate cells[J]. Antioxid Redox Signal, 2011, 15( 10): 2711- 2722. DOI: 10.1089/ars.2011.4079.
    [28] RAMAKRISHNAN P, LOH WM, GOPINATH SCB, et al. Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer[J]. Acta Pharm Sin B, 2020, 10( 3): 399- 413. DOI: 10.1016/j.apsb.2019.11.008.
    [29] BYNIGERI RR, JAKKAMPUDI A, JANGALA R, et al. Pancreatic stellate cell: Pandora’s box for pancreatic disease biology[J]. World J Gastroenterol, 2017, 23( 3): 382- 405. DOI: 10.3748/wjg.v23.i3.382.
    [30] ARUMUGAM T, BRANDT W, RAMACHANDRAN V, et al. Trefoil factor 1 stimulates both pancreatic cancer and stellate cells and increases metastasis[J]. Pancreas, 2011, 40( 6): 815- 822. DOI: 10.1097/MPA.0b013e31821f6927.
    [31] LEE SH, PARK SY, CHOI CS. Insulin resistance: From mechanisms to therapeutic strategies[J]. Diabetes Metab J, 2022, 46( 1): 15- 37. DOI: 10.4093/dmj.2021.0280.
    [32] OLESEN SS, SVANE HML, NICOLAISEN SK, et al. Clinical and biochemical characteristics of postpancreatitis diabetes mellitus: A cross-sectional study from the Danish nationwide DD2 cohort[J]. J Diabetes, 2021, 13( 12): 960- 974. DOI: 10.1111/1753-0407.13210.
    [33] ASLAM M, VIJAYASARATHY K, TALUKDAR R, et al. Reduced pancreatic polypeptide response is associated with early alteration of glycemic control in chronic pancreatitis[J]. Diabetes Res Clin Pract, 2020, 160: 107993. DOI: 10.1016/j.diabres.2019.107993.
    [34] HENNIG R, KEKIS PB, FRIESS H, et al. Pancreatic polypeptide in pancreatitis[J]. Peptides, 2002, 23( 2): 331- 338. DOI: 10.1016/s0196-9781(01)00605-2.
    [35] GOODARZI MO, PETROV MS. Diabetes of the exocrine pancreas: Implications for pharmacological management[J]. Drugs, 2023, 83( 12): 1077- 1090. DOI: 10.1007/s40265-023-01913-5.
    [36] GOLDSTEIN JA, KIRWIN JD, SEYMOUR NE, et al. Reversal of in vitro hepatic insulin resistance in chronic pancreatitis by pancreatic polypeptide in the rat[J]. Surgery, 1989, 106( 6): 1128-1132; discussion 1132-1133.
    [37] CAI DS, YUAN MS, FRANTZ DF, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB[J]. Nat Med, 2005, 11( 2): 183- 190. DOI: 10.1038/nm1166.
    [38] HEO YJ, CHOI SE, JEON JY, et al. Visfatin induces inflammation and insulin resistance via the NF-κB and STAT3 signaling pathways in hepatocytes[J]. J Diabetes Res, 2019, 2019: 4021623. DOI: 10.1155/2019/4021623.
    [39] SAH RP, NAGPAL SJ, MUKHOPADHYAY D, et al. New insights into pancreatic cancer-induced paraneoplastic diabetes[J]. Nat Rev Gastroenterol Hepatol, 2013, 10( 7): 423- 433. DOI: 10.1038/nrgastro.2013.49.
    [40] YARIBEYGI H, FARROKHI FR, BUTLER AE, et al. Insulin resistance: Review of the underlying molecular mechanisms[J]. J Cell Physiol, 2019, 234( 6): 8152- 8161. DOI: 10.1002/jcp.27603.
    [41] ZHOU XL, YOU SY. Rosiglitazone inhibits hepatic insulin resistance induced by chronic pancreatitis and IKK-β/NF-κB expression in liver[J]. Pancreas, 2014, 43( 8): 1291- 1298. DOI: 10.1097/MPA.0000000000000173.
    [42] WENTWORTH JM, ZHANG JG, BANDALA-SANCHEZ E, et al. Interferon-gamma released from omental adipose tissue of insulin-resistant humans alters adipocyte phenotype and impairs response to insulin and adiponectin release[J]. Int J Obes, 2017, 41( 12): 1782- 1789. DOI: 10.1038/ijo.2017.180.
    [43] REHMAN K, AKASH MSH, LIAQAT A, et al. Role of interleukin-6 in development of insulin resistance and type 2 diabetes mellitus[J]. Crit Rev Eukaryot Gene Expr, 2017, 27( 3): 229- 236. DOI: 10.1615/CritRevEukaryotGeneExpr.2017019712.
    [44] AKBARI M, HASSAN-ZADEH V. IL-6 signalling pathways and the development of type 2 diabetes[J]. Inflammopharmacology, 2018, 26( 3): 685- 698. DOI: 10.1007/s10787-018-0458-0.
    [45] DOU L, ZHAO T, WANG LL, et al. MiR-200s contribute to interleukin-6(IL-6)-induced insulin resistance in hepatocytes[J]. J Biol Chem, 2013, 288( 31): 22596- 22606. DOI: 10.1074/jbc.M112.423145.
    [46] DOU L, WANG SY, SUI XF, et al. MiR-301a mediates the effect of IL-6 on the AKT/GSK pathway and hepatic glycogenesis by regulating PTEN expression[J]. Cell Physiol Biochem, 2015, 35( 4): 1413- 1424. DOI: 10.1159/000373962.
    [47] CHEANG JY, MOYLE PM. Glucagon-like peptide-1(GLP-1)-based therapeutics: Current status and future opportunities beyond type 2 diabetes[J]. ChemMedChem, 2018, 13( 7): 662- 671. DOI: 10.1002/cmdc.201700781.
    [48] TUDURÍ E, LÓPEZ M, DIÉGUEZ C, et al. Glucagon-like peptide 1 analogs and their effects on pancreatic islets[J]. Trends Endocrinol Metab, 2016, 27( 5): 304- 318. DOI: 10.1016/j.tem.2016.03.004.
    [49] DRUCKER DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1[J]. Cell Metab, 2018, 27( 4): 740- 756. DOI: 10.1016/j.cmet.2018.03.001.
    [50] ZHOU Z, SUN B, YU DS, et al. Gut microbiota: An important player in type 2 diabetes mellitus[J]. Front Cell Infect Microbiol, 2022, 12: 834485. DOI: 10.3389/fcimb.2022.834485.
    [51] TILG H, ZMORA N, ADOLPH TE, et al. The intestinal microbiota fuelling metabolic inflammation[J]. Nat Rev Immunol, 2020, 20( 1): 40- 54. DOI: 10.1038/s41577-019-0198-4.
    [52] TAO J, CHEEMA H, KESH K, et al. Chronic pancreatitis in a caerulein-induced mouse model is associated with an altered gut microbiome[J]. Pancreatology, 2022, 22( 1): 30- 42. DOI: 10.1016/j.pan.2021.12.003.
    [53] ARON-WISNEWSKY J, WARMBRUNN MV, NIEUWDORP M, et al. Metabolism and metabolic disorders and the microbiome: The intestinal microbiota associated with obesity, lipid metabolism, and metabolic health-pathophysiology and therapeutic strategies[J]. Gastroenterology, 2021, 160( 2): 573- 599. DOI: 10.1053/j.gastro.2020.10.057.
    [54] TALUKDAR R, SARKAR P, JAKKAMPUDI A, et al. The gut microbiome in pancreatogenic diabetes differs from that of Type 1 and Type 2 diabetes[J]. Sci Rep, 2021, 11( 1): 10978. DOI: 10.1038/s41598-021-90024-w.
    [55] JANDHYALA SM, MADHULIKA A, DEEPIKA G, et al. Altered intestinal microbiota in patients with chronic pancreatitis: Implications in diabetes and metabolic abnormalities[J]. Sci Rep, 2017, 7: 43640. DOI: 10.1038/srep43640.
    [56] ZOU WB, TANG XY, ZHOU DZ, et al. SPINK1, PRSS1, CTRC, and CFTR genotypes influence disease onset and clinical outcomes in chronic pancreatitis[J]. Clin Transl Gastroenterol, 2018, 9( 11): 204. DOI: 10.1038/s41424-018-0069-5.
    [57] CHEN JM, FÉREC C. Genetics and pathogenesis of chronic pancreatitis: The 2012 update[J]. Clin Res Hepatol Gastroenterol, 2012, 36( 4): 334- 340. DOI: 10.1016/j.clinre.2012.05.003.
    [58] MASSON E, CHEN JM, AUDRÉZET MP, et al. A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: Data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients[J]. PLoS One, 2013, 8( 8): e73522. DOI: 10.1371/journal.pone.0073522.
    [59] LIU QC, ZHUANG ZH, ZENG K, et al. Prevalence of pancreatic diabetes in patients carrying mutations or polymorphisms of the PRSS1 gene in the Han population[J]. Diabetes Technol Ther, 2009, 11( 12): 799- 804. DOI: 10.1089/dia.2009.0051.
  • 加载中
图(1)
计量
  • 文章访问数:  95
  • HTML全文浏览量:  56
  • PDF下载量:  11
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-11-23
  • 录用日期:  2024-01-02
  • 出版日期:  2024-08-25
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回