Skip to content
2000
Volume 25, Issue 9
  • ISSN: 1871-5303
  • E-ISSN: 2212-3873

Abstract

Aim

To discover new therapeutic targets for Type 2 diabetes (T2D) and develop a new diagnostic model.

Background

T2D is a chronic disease that can be controlled by oral hypoglycemic drugs, however, it cannot be fully cured. The continued increase in the prevalence of T2D and the limitations of existing treatments urgently call for the development of new drugs to be able to effectively control the progression of the disease.

Objective

We aimed to discover new therapeutic targets for T2D and to develop a new diagnostic model.

Methods

Single-cell transcriptome, web-based systematic pharmacology, and transcriptology were applied to identify T2D diagnostic targets and drug candidates and to analyze the underlying molecular mechanisms.

Results

By single-cell clustering analysis, we identified seven subsets between the normal islet β-cell samples and T2D islet β-cell samples. A total of 27 key genes in the intersection of insulin-related genes and diabetes-related genes were selected by protein-protein interaction (PPI) analysis and MolecularComplexDetection (MCODE) analysis. Notably, , and had the area under curves (AUC) values as high as 67.95%, 66.67%, and 66.03% for the diagnosis of T2D, respectively. Since the expression of in T2D samples was significantly higher than in normal samples, we screened 155 drug candidates against in T2D. Finally, the molecular docking revealed a strong binding strength between and DB05490, which was one of the most effective candidate drugs for treating T2D.

Conclusion

Our study screens for diagnostic signatures and potential therapeutic agents for T2D, which provides valuable insights into the development of T2D biomarkers and their drug discovery.

Loading

Article metrics loading...

/content/journals/emiddt/10.2174/0118715303331820240820072804
2024-08-22
2025-09-24
Loading full text...

Full text loading...

References

  1. HureauxM. Vargas-PoussouR. Genetic basis of nephrogenic diabetes insipidus.Mol. Cell. Endocrinol.202356011182510.1016/j.mce.2022.111825 36460218
    [Google Scholar]
  2. DuX. ShiH. LiuH. ZhouL. XieA. GuoJ. Angiogenic gene PTK2 is a potential biomarker of gestational diabetes mellitus and is significantly associated with breast cancer immune infiltration.Oncologie202224476978710.32604/oncologie.2022.026248
    [Google Scholar]
  3. ZhongJ. MaoX. LiH. ShenG. CaoX. HeN. WangJ. XuL. ChenJ. SongX. LiuS. ZhangX. ShenY. WangL. XiangC. ChenY. Single-cell RNA sequencing analysis reveals the relationship of bone marrow and osteopenia in STZ-induced type 1 diabetic mice.J. Adv. Res.20224114515810.1016/j.jare.2022.01.006 36328744
    [Google Scholar]
  4. MajetyP. Lozada OrqueraF.A. EdemD. HamdyO. Pharmacological approaches to the prevention of type 2 diabetes mellitus.Front. Endocrinol.202314111884810.3389/fendo.2023.1118848 36967777
    [Google Scholar]
  5. DeutschA.J. SchroederP.H. MandlaR. KangS. ErenlerF. MercaderJ.M. UdlerM.S. FlorezJ.C. BrennerL.N. Type 2 diabetes polygenic score predicts the risk of glucocorticoid-induced hyperglycemia in patients without diabetes.Diabetes Care20234681541154510.2337/dc23‑0353 37353344
    [Google Scholar]
  6. HeP. LiH. YeZ. LiuM. ZhouC. WuQ. ZhangY. YangS. ZhangY. QinX. Association of a healthy lifestyle, life’s essential 8 scores with incident macrovascular and microvascular disease among individuals with type 2 diabetes.J. Am. Heart Assoc.20231217e02944110.1161/JAHA.122.029441 37609934
    [Google Scholar]
  7. AlkabbaniW. MaxwellC.J. MarrieR.A. TyasS.L. LegaI.C. GambleJ.M. Insulin use in type 2 diabetes and the risk of dementia: A comparative population-based cohort study.Diabetes Care20234681492150010.2337/dc23‑0222 37315211
    [Google Scholar]
  8. WexlerD.J. de BoerI.H. GhoshA. YounesN. BebuI. InzucchiS.E. McGillJ.B. MudaliarS. SchadeD. SteffesM.W. TamborlaneW.V. TanM.H. Ismail-BeigiF. CrandallJ.P. McKeeM.D. Beringher-MasseraS. Brown-FridayJ. XhoriE. Ballentine-CargillK. DuranS. EstrellaH. Gonzalez de la torre, S.; Lukin, J.; Phillips, L.; Burgess, E.; Olson, D.; Rhee, M.; Wilson, P.; Raines, T.S.; Boers, J.; Costello, J.; Maher-Albertelli, M.; Mungara, R.; Savoye, L.; White, C.A.; Gullett, C.; Holloway, L.; Morehead, F.; Person, S.; Sibymon, M.; Tanukonda, S.; Adams, C.; Ross, A.; Balasubramanyam, A.; Gaba, R.; Gonzalez, E.; Ideozu, A.; Jimenez, J.; Montes, G.; Wright, C.; Hollander, P.; Roe, E.; Jackson, A.; Smiley, A.; Burt, P.; Estrada, L.; Chionh, K.; Ismail-Beigi, F.; Falck-Ytter, C.; Sayyed Kassem, L.; Sood, A.; Tiktin, M.; Cramer, B.; Iacoboni, J.; Kononets, M.V.; Kulow, T.; Newman, C.; Stancil, K.A.; Sanders, C.; Tucker, L.; Werner, A.; Krol, A.; McPhee, G.; Patel, C.; Colosimo, L.; Maxwell, A.; Goland, R.; Pring, J.; Alfano, L.; Kringas, P.; Hausheer, C.; Tejada, J.; Gumpel, K.; Kirpitch, A.; Schneier, H.; Green, J.B.; AbouAssi, H.; Chatterjee, R.; Feinglos, M.N.; English Jones, J.; Khan, S.A.; Kimpel, J.B.; Zimmer, R.P.; Furst, M.; Satterwhite, B.M.; Thacker, C.R.; Evans Kreider, K.; Mariash, C.N.; Mather, K.J.; Ismail, H.M.; Lteif, A.; Mullen, M.; Hamilton, T.; Patel, N.; Riera, G.; Jackson, M.; Pirics, V.; Howard, D.; Aguillar, D.; Hurt, S.; Bergenstal, R.; Carlson, A.; Martens, T.; Johnson, M.; Hill, R.; Hyatt, J.; Jensen, C.; Madden, M.; Martin, D.; Willis, H.; Konerza, W.; Yang, S.; Passi, R.; Kleeberger, K.; Fortmann, S.; Herson, M.; Mularski, K.; Glauber, H.; Prihoda, J.; Ash, B.; Carlson, C.; Ramey, P.A.; Schield, E.; Torgrimson-Ojerio, B.; Arnold, K.; Kauffman, B.; Panos, E.; Sahnow, S.; Bays, K.; Cook, J.; Gluth, J.; Ghioni, D.; Schell, K.; Criscola, J.; Friason, C.; Jones, S.; Nazarov, S.; Barzilay, J.; Rassouli, N.; Puttnam, R.; Ojoawo, O.; Nelson, R.; Curtis, M.; Hollis, B.; Sanders-Jones, C.; Stokes, K.; El-Haqq, Z.; Kolli, A.; Tran, T.; Wexler, D.; Larkin, M.; Meigs, J.; Chambers, B.; Dushkin, A.; Rocchio, G.; Yepes, M.; Steiner, B.; Dulin, H.; Cayford, M.; DeManbey, A.; Hillard, M.; Martin, K.; Thangthaeng, N.; Gurry, L.; Kochis, R.; Raymond, E.; Ripley, V.; Stevens, C.; Park, J.; Aroda, V.; Ghazi, A.; Magee, M.; Ressing, A.; Loveland, A.; Hamm, M.; Hurtado, M.; Kuhn, A.; Leger, J.L.; Manandhar, L.; Mwicigi, F.; Sanchez, O.; Young, T.; Garg, R.; Lagari-Libhaber, V.; Florez, H.J.; Valencia, W.M.; Mark, J.; Casula, S.; Oropesa-Gonzalez, L.; Hue, L.; Cuadot, A.; Nieto-Martinez, R.; Riccio Veliz, A.K.; Gutt, M.; Kendal, Y.J.; Veciana, B.; Ahmann, A.; Aby-Daniel, D.; Joarder, F.; Morimoto, V.; Sprague, C.; Yamashita, D.; Cady, N.; Rivera-Eschright, N.; Kirchhoff, P.; Morales Gonzalez, B.; Adducci, J.; Goncharova, A.; Hox, S.H.; Petrovich, H.; Matwichyna, M.; Jenkins, V.; Broadwater, L.; Ishii, R.R.; Bermudez, N.O.; Hsia, D.S.; Cefalu, W.T.; Greenway, F.L.; Waguespack, C.; King, E.; Fry, G.; Dragg, A.; Gildersleeve, B.; Arceneaux, J.; Haynes, N.; Thomassie, A.; Pavlionis, M.; Bourgeois, B.; Hazlett, C.; Mudaliar, S.; Robert, H.; Boeder, S.; Pettus, J.; Diaz, E.; Garcia-Acosta, D.; Maggs, S.; DeLue, C.; Stallings, A.; Castro, E.; Hernandez, S.; Krakoff, J.; Curtis, J.M.; Killean, T.; Khalid, M.; Joshevama, E.; Diaz, E.; Martin, D.; Tsingine, K.; Karshner, T.; Albu, J.; Pi-Sunyer, F.X.; Frances, S.; Maggio, C.; Ellis, E.; Bastawrose, J.; Gong, X.; Banerji, M.A.; August, P.; Lee, M.; Lorber, D.; Necole M, B.; Josephson, D.H.; Thomas, L.L.; Tsovian, M.; Cherian, A.; Jacobson, M.H.; Mishko, M.M.; Kirkman, S.M.; Buse, J.B.; Dostou, J.; Machineni, S.; Young, L.; Bergamo, K.; Goley, A.; Kerr, J.; Largay, J.F.; Guarda, S.; Cuffee, J.; Culmer, D.; Fraser, R.; Almeida, H.; Coffer, S.; Debnam, E.; Kiker, L.; Morton, S.; Josey, K.; Fuller, G.; Garvey, W.T.; Cherrington, A.L.; Dyer, D.; Lawson, M.C.R.; Griffith, O.; Agne, A.; McCullars, S.; Cohen, R.M.; Craig, J.; Rogge, M.C.; Burton, K.; Kersey, K.; Wilson, C.; Lipp, S.; Vonder Meulen, M.B.; Adkins, C.; Onadeko, T.; Rasouli, N.; Baker, C.; Schroeder, E.; Razzaghi, M.; Lyon, C.; Penaloza, R.; Underkofler, C.; Lorch, R.; Douglass, S.; Steiner, S.; Sivitz, W.; Cline, E.; Knosp, L.K.; McConnell, J.; Lowe, T.; Herman, W.H.; Pop-Busui, R.; Tan, M.H.; Martin, C.; Waltje, A.; Katona, A.; Goodhall, L.; Eggleston, R.; Kuo, S.; Bojescu, S.; Bule, S.; Kessler, N.; LaSalle, E.; Whitley, K.; Seaquist, E.R.; Bantle, A.; Harindhanavudhi, T.; Kumar, A.; Redmon, B.; Bantle, J.; Coe, M.; Mech, M.; Taddese, A.; Lesne, L.; Smith, S.; Desouza, C.; Kuechenmeister, L.; Shivaswamv, V.; Burbach, S.; Rodriguez, M.G.; Seipel, K.; Alfred, A.; Morales, A.L.; Eggert, J.; Lord, G.; Taylor, W.; Tillson, R.; Schade, D.S.; Adolphe, A.; Burge, M.; Duran-Valdez, E.; Martinez, J.; Bancroft, A.; Kunkel, S.; Jamaleddin Ahmad, F.A.; Hernandez McGinnis, D.; Pucchetti, B.; Scripsick, E.; Zamorano, A.; DeFronzo, R.A.; Cersosimo, E.; Abdul-Ghani, M.; Triplitt, C.; Juarez, D.; Garza, R.I.; Verastiqui, H.; Wright, K.; Puckett, C.; Raskin, P.; Rhee, C.; Abraham, S.; Jordan, L.F.; Sao, S.; Morton, L.; Smith, O.; Osornio Walker, L.; Schnurr-Breen, L.; Ayala, R.I.; Kreymer, R.B.; Sturgess, D.; Utzschneider, K.M.; Kahn, S.E.; Alarcon-Casas Wright, L.; Boyko, E.J.; Tsiai, E.C.; Trence, D.L.; Trikudanathan, S.; Fattaleh, B.N.; Montgomery, B.K.; Atkinson, K.M.; Kozedub, A.; Concepcion, T.; Moak, C.; Prikhodko, N.; Rhothisen, S.; Elasy, T.A.; Martin, S.; Shackelford, L.; Goidel, R.; Hinkle, N.; Lovell, C.; Myers, J.; Lipps Hogan, J.; McGill, J.B.; Salam, M.; Schweiger, T.; Kissel, S.; Recklein, C.; Clifton, M.J.; Tamborlane, W.; Camp, A.; Gulanski, B.; Inzucchi, S.E.; Pham, K.; Alguard, M.; Gatcomb, P.; Lessard, K.; Perez, M.; Iannone, L.; Magenheimer, E.; Montosa, A.; Cefalu, W.T.; Fradkin, J.; Burch, H.B.; Bremer, A.; Nathan, D.M.; Lachin, J.M.; Krause-Steinrauf, H.; Younes, N.; Bebu, I.; Butera, N.; Buys, C.J.; Fagan, A.; Gao, Y.; Ghosh, A.; Gramzinski, M.R.; Hall, S.D.; Kazemi, E.; Legowski, E.; Liu, H.; Suratt, C.E.; Tripputi, M.; Arey, A.; Backman, M.; Bethepu, J.; Lund, C.; Mangat Dhaliwal, P.; McGee, P.; Mesimer, E.; Ngo, L.; Steffes, M.; Seegmiller, J.; Saenger, A.; Arends, V.; Gabrielson, D.; Conner, T.; Warren, S.; Day, J.; Huminik, J.; Scrymgeour, A.; Soliman, E.Z.; Pokharel, Y.; Zhang, Z-M.; Campbell, C.; Hu, J.; Keasler, L.; Hensley, S.; Li, Y.; Mihalcea, R.; Min, D.J.; Perez-Rosas, V.; Prosser, L.; Resnicow, K.; Ye, W.; Shao, H.; Zhang, P.; Luchsinger, J.; Sanchez, D.; Assuras, S.; Groessl, E.; Sakha, F.; Chong, H.; Hillery, N.; Abdouch, I.; Bahityar, G.; Brantley, P.; Broyles, F.E.; Canaris, G.; Copeland, P.; Craine, J.J.; Fein, W.L.; Gliwa, A.; Hope, L.M.; Lee, M.S.; Meiners, R.; Meiners, V.; O’Neal, H.; Park, J.E.; Sacerdote, A.; Sledge, E., Jr; Soni, L.; Steppel-Reznik, J.; Turchin, A. Comparative effects of glucose-lowering medications on kidney outcomes in type 2 diabetes.JAMA Intern. Med.2023183770571410.1001/jamainternmed.2023.1487 37213109
    [Google Scholar]
  9. SuJ. LuoY. HuS. TangL. OuyangS. Advances in research on type 2 diabetes mellitus targets and therapeutic agents.Int. J. Mol. Sci.202324171338110.3390/ijms241713381 37686185
    [Google Scholar]
  10. SahayR.K. GiriR. ShembalkarJ.V. GuptaS.K. MohanB. KurmiP. KumarS.R. SawardekarV.M. MishraA. MurthyL.S. AryaV.V. SonawaneA.R. SoniP.N. GofneS.K. KarnawatS.R. RajurkarM.N. PatelP.M. LakhwaniL.K. MehtaS.C. JoglekarS.J. Fixed-dose combination of dapagliflozin + sitagliptin + metformin in patients with type 2 diabetes poorly controlled with metformin: Phase 3, randomized comparison with dual combinations.Adv. Ther.20234073227324610.1007/s12325‑023‑02523‑z 37258803
    [Google Scholar]
  11. JainA. VisputeA. DangeA. NaskarA. MondalA. VivekanandB. SharmaB. VaradeD. ShuklaD. BhatiaG. ChaudhariH. Ram BabuK. GavaliO. SorateS. BhanushaliS. KothariV. KhandelwalV. SharmaA. PawarR. MayabhateM. ShahaviV. RajputA. JaiswalM. RandomizedA. A randomized, double-blind, parallel-group phase III trial investigating the glycemic efficacy and safety profile of fixed-dose combination dapagliflozin and linagliptin over linagliptin monotherapy in patients with inadequately controlled type 2 diabetes with metformin.Diabetes Ther.202415121522710.1007/s13300‑023‑01504‑3 37957465
    [Google Scholar]
  12. SoldovieriL. Di GiuseppeG. CiccarelliG. QueroG. CintiF. BrunettiM. NistaE.C. GasbarriniA. AlfieriS. PontecorviA. GiaccariA. MezzaT. An update on pancreatic regeneration mechanisms: Searching for paths to a cure for type 2 diabetes.Mol. Metab.20237410175410.1016/j.molmet.2023.101754 37321370
    [Google Scholar]
  13. NiY. XiongR. ZhuY. LuanN. YuC. YangK. WangH. XuX. YangY. SunS. ShiL. PaddeJ.R. ChenL. ChenL. HouM. XuZ. LaiR. JiM. A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases.EBioMedicine20239510475110.1016/j.ebiom.2023.104751 37579625
    [Google Scholar]
  14. ZhouJ.Q. ZengL.H. LiC.T. HeD.H. ZhaoH.D. XuY.N. JinZ.T. GaoC. Brain organoids are new tool for drug screening of neurological diseases.Neural Regen. Res.202318918841889 36926704
    [Google Scholar]
  15. AtharM. ManhasA. RanaN. IrfanA. Computational and bioinformatics tools for understanding disease mechanisms.Biocell202448693594410.32604/biocell.2024.049891
    [Google Scholar]
  16. TrajanoskaK. BhérerC. TaliunD. ZhouS. RichardsJ.B. MooserV. From target discovery to clinical drug development with human genetics.Nature2023620797573774510.1038/s41586‑023‑06388‑8 37612393
    [Google Scholar]
  17. ArteP.A. TungareK. BhoriM. JobbyR. AichJ. Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach.Hum. Cell2023371548410.1007/s13577‑023‑01007‑0 38038863
    [Google Scholar]
  18. RiveraC.N. HinkleJ.S. WatneR.M. MacgowanT.C. WommackA.J. VaughanR.A. PPARβ/δ agonism with gw501516 increases myotube PGC-1α content and reduces BCAA media content independent of changes in BCAA catabolic enzyme expression.PPAR Res.2023202312010.1155/2023/4779199 37325367
    [Google Scholar]
  19. HryciwD.H. PattenR.K. RodgersR.J. ProiettoJ. HutchinsonD.S. McAinchA.J. GPR119 agonists for type 2 diabetes: Past failures and future hopes for preclinical and early phase candidates.Expert Opin. Investig. Drugs202433318319010.1080/13543784.2024.2321271 38372052
    [Google Scholar]
  20. LuY. HuangR. SunZ. OuY. A bovine milk-derived peptide ameliorates pancreatic β-cell dedifferentiation through PI3K/Akt/FOXO1 signaling in type 2 diabetes.Food Funct.202314178018802910.1039/D3FO01330H 37593938
    [Google Scholar]
  21. ChengL. ShiL. HeC. WangC. LvY. LiH. an, Y.; Duan, Y.; Dai, H.; Zhang, H.; Huang, Y.; Fu, W.; Sun, W.; Zhao, B. Mulberry leaf flavonoids activate BAT and induce browning of WAT to improve type 2 diabetes via regulating the AMPK/SIRT1/PGC-1α signaling pathway.Chin. J. Nat. Med.2023211181282910.1016/S1875‑5364(23)60481‑9 38035937
    [Google Scholar]
  22. ZulibiyaA. WenJ. YuH. ChenX. XuL. MaX. ZhangB. Single-cell RNA sequencing reveals potential for endothelial-to-mesenchymal transition in tetralogy of fallot.Congenit. Heart Dis.202318661162510.32604/chd.2023.047689
    [Google Scholar]
  23. KodousA.S. BalaiahM. RamanathanP. Single cell RNA sequencing – A valuable tool for cancer immunotherapy: A mini review.Oncologie202325663563910.1515/oncologie‑2023‑0244
    [Google Scholar]
  24. TangH. WangJ. DengP. LiY. CaoY. YiB. ZhuL. ZhuS. LuY. Transcriptome-wide association study-derived genes as potential visceral adipose tissue-specific targets for type 2 diabetes.Diabetologia202366112087210010.1007/s00125‑023‑05978‑5 37540242
    [Google Scholar]
  25. ChenS. LiB. ChenL. JiangH. Uncovering the mechanism of resveratrol in the treatment of diabetic kidney disease based on network pharmacology, molecular docking, and experimental validation.J. Transl. Med.202321138010.1186/s12967‑023‑04233‑0 37308949
    [Google Scholar]
  26. DemirsoyI. KaraibrahimogluA. Identifying drug interactions using machine learning.Adv. Clin. Exp. Med.2023328829838
    [Google Scholar]
  27. SongZ. YuJ. WangM. ShenW. WangC. LuT. ShanG. DongG. WangY. ZhaoJ. CHDTEPDB: Transcriptome expression profile database and interactive analysis platform for congenital heart disease.Congenit. Heart Dis.202318669370110.32604/chd.2024.048081
    [Google Scholar]
  28. McGuireD.K. BusuiR.P. DeanfieldJ. InzucchiS.E. MannJ.F.E. MarxN. MulvaghS.L. PoulterN. EngelmannM.D.M. HovinghG.K. RipaM.S. GislumM. Brown-FrandsenK. BuseJ.B. Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial.Diabetes Obes. Metab.20232571932194110.1111/dom.15058 36945734
    [Google Scholar]
  29. LunatiM.E. CiminoV. BernasconiD. GandolfiA. MorpurgoP.S. TinariC. LazzaroniE. BaruffaldiL. MuratoriM. MontefuscoL. PastoreI. RossiA. FranzettiI.G. MuratoriF. ManfriniR. DisoteoO.E. TerranovaR. DesenzaniP. GirelliA. GhelardiR. D’AddioF. Ben NasrM. BerraC. FolliF. BucciarelliL. FiorinaP. Type 2 diabetes mellitus pharmacological remission with dapagliflozin plus oral semaglutide.Pharmacol. Res.202419910704010.1016/j.phrs.2023.107040 38128857
    [Google Scholar]
  30. DelibegovićM. Dall’AngeloS. DekeryteR. Protein tyrosine phosphatase 1B in metabolic diseases and drug development.Nat. Rev. Endocrinol.202420636637810.1038/s41574‑024‑00965‑1 38519567
    [Google Scholar]
  31. SuzukiK. HatzikotoulasK. SouthamL. TaylorH.J. YinX. LorenzK.M. MandlaR. Huerta-ChagoyaA. MelloniG.E.M. KanoniS. RaynerN.W. BocherO. ArrudaA.L. SoneharaK. NambaS. LeeS.S.K. PreussM.H. PettyL.E. SchroederP. VanderwerffB. KalsM. BraggF. LinK. GuoX. ZhangW. YaoJ. KimY.J. GraffM. TakeuchiF. NanoJ. LamriA. NakatochiM. MoonS. ScottR.A. CookJ.P. LeeJ.J. PanI. TaliunD. ParraE.J. ChaiJ.F. BielakL.F. TabaraY. HaiY. ThorleifssonG. GrarupN. SoferT. WuttkeM. SarnowskiC. GiegerC. NousomeD. TrompetS. KwakS.H. LongJ. SunM. TongL. ChenW.M. NongmaithemS.S. NoordamR. LimV.J.Y. TamC.H.T. JooY.Y. ChenC.H. RaffieldL.M. PrinsB.P. NicolasA. YanekL.R. ChenG. BrodyJ.A. KabagambeE. AnP. XiangA.H. ChoiH.S. CadeB.E. TanJ. BroadawayK.A. WilliamsonA. KamaliZ. CuiJ. ThangamM. AdairL.S. AdeyemoA. Aguilar-SalinasC.A. AhluwaliaT.S. AnandS.S. BertoniA. Bork-JensenJ. BrandslundI. BuchananT.A. BurantC.F. ButterworthA.S. CanouilM. ChanJ.C.N. ChangL.C. CheeM.L. ChenJ. ChenS.H. ChenY.T. ChenZ. ChuangL.M. CushmanM. DaneshJ. DasS.K. de SilvaH.J. DedoussisG. DimitrovL. DoumateyA.P. DuS. DuanQ. EckardtK.U. EmeryL.S. EvansD.S. EvansM.K. FischerK. FloydJ.S. FordI. FrancoO.H. FraylingT.M. FreedmanB.I. GenterP. GersteinH.C. GiedraitisV. González-VillalpandoC. González-VillalpandoM.E. Gordon-LarsenP. GrossM. GuareL.A. HackingerS. HakasteL. HanS. HattersleyA.T. HerderC. HorikoshiM. HowardA.G. HsuehW. HuangM. HuangW. HungY.J. HwangM.Y. HwuC.M. IchiharaS. IkramM.A. IngelssonM. IslamM.T. IsonoM. JangH.M. JasmineF. JiangG. JonasJ.B. JørgensenT. KamanuF.K. KandeelF.R. KasturiratneA. KatsuyaT. KaurV. KawaguchiT. KeatonJ.M. KhoA.N. KhorC.C. KibriyaM.G. KimD.H. KronenbergF. KuusistoJ. LällK. LangeL.A. LeeK.M. LeeM.S. LeeN.R. LeongA. LiL. LiY. Li-GaoR. LigthartS. LindgrenC.M. LinnebergA. LiuC.T. LiuJ. LockeA.E. LouieT. LuanJ. LukA.O. LuoX. LvJ. LynchJ.A. LyssenkoV. MaedaS. MamakouV. MansuriS.R. MatsudaK. MeitingerT. MelanderO. MetspaluA. MoH. MorrisA.D. MouraF.A. NadlerJ.L. NallsM.A. NayakU. NtallaI. OkadaY. OrozcoL. PatelS.R. PatilS. PeiP. PereiraM.A. PetersA. PirieF.J. PolikowskyH.G. PornealaB. PrasadG. Rasmussen-TorvikL.J. ReinerA.P. RodenM. RohdeR. RollK. SabanayagamC. SandowK. SankareswaranA. SattarN. SchönherrS. ShahriarM. ShenB. ShiJ. ShinD.M. ShojimaN. SmithJ.A. SoW.Y. StančákováA. SteinthorsdottirV. StilpA.M. StrauchK. TaylorK.D. ThorandB. ThorsteinsdottirU. TomlinsonB. TranT.C. TsaiF.J. TuomilehtoJ. Tusie-LunaT. UdlerM.S. Valladares-SalgadoA. van DamR.M. van KlinkenJ.B. VarmaR. Wacher-RodarteN. WheelerE. WickremasingheA.R. van DijkK.W. WitteD.R. YajnikC.S. YamamotoK. YamamotoK. YoonK. YuC. YuanJ.M. YusufS. ZawistowskiM. ZhangL. ZhengW. KanonaS. van HeelD.A. RaffelL.J. IgaseM. IppE. RedlineS. ChoY.S. LindL. ProvinceM.A. FornageM. HanisC.L. IngelssonE. ZondermanA.B. PsatyB.M. WangY-X. RotimiC.N. BeckerD.M. MatsudaF. LiuY. YokotaM. KardiaS.L.R. PeyserP.A. PankowJ.S. EngertJ.C. BonnefondA. FroguelP. WilsonJ.G. SheuW.H.H. WuJ-Y. HayesM.G. MaR.C.W. WongT-Y. Mook-KanamoriD.O. TuomiT. ChandakG.R. CollinsF.S. BharadwajD. ParéG. SaleM.M. AhsanH. MotalaA.A. ShuX-O. ParkK-S. JukemaJ.W. CruzM. ChenY-D.I. RichS.S. McKean-CowdinR. GrallertH. ChengC-Y. GhanbariM. TaiE-S. DupuisJ. KatoN. LaaksoM. KöttgenA. KohW-P. BowdenD.W. PalmerC.N.A. KoonerJ.S. KooperbergC. LiuS. NorthK.E. SaleheenD. HansenT. PedersenO. WarehamN.J. LeeJ. KimB-J. MillwoodI.Y. WaltersR.G. StefanssonK. AhlqvistE. GoodarziM.O. MohlkeK.L. LangenbergC. HaimanC.A. LoosR.J.F. FlorezJ.C. RaderD.J. RitchieM.D. ZöllnerS. MägiR. MarstonN.A. RuffC.T. van HeelD.A. FinerS. DennyJ.C. YamauchiT. KadowakiT. ChambersJ.C. NgM.C.Y. SimX. BelowJ.E. TsaoP.S. ChangK-M. McCarthyM.I. MeigsJ.B. MahajanA. SpracklenC.N. MercaderJ.M. BoehnkeM. RotterJ.I. VujkovicM. VoightB.F. MorrisA.P. ZegginiE. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.Nature2024627800334735710.1038/s41586‑024‑07019‑6 38374256
    [Google Scholar]
  32. CondeS.V. SacramentoJ.F. ZinnoC. MazzoniA. MiceraS. GuarinoM.P. Bioelectronic modulation of carotid sinus nerve to treat type 2 diabetes: Current knowledge and future perspectives.Front. Neurosci.202418137847310.3389/fnins.2024.1378473 38646610
    [Google Scholar]
  33. LiG. WangQ. ChenX. YuP. PengQ. ChenH. RenS. WangC. SuY. LiangX. SunM. DuX. HeR. Based on network pharmacology to explore the effect and mechanism of Yipibushen decoction in improving obese type 2 diabetes mellitus with oligoasthenotspermia.J. Ethnopharmacol.202331711673810.1016/j.jep.2023.116738 37369336
    [Google Scholar]
  34. SabarathinamS. GanamuraliN. Chalcones reloaded: An integration of network pharmacology and molecular docking for type 2 diabetes therapy.J. Biomol. Struct. Dyn.202311310.1080/07391102.2023.2252085 37643025
    [Google Scholar]
  35. DingJ. LiC. ShuK. ChenW. CaiC. ZhangX. ZhangW. Membrane metalloendopeptidase (MME) is positively correlated with systemic lupus erythematosus and may inhibit the occurrence of breast cancer.PLoS One2023188e028996010.1371/journal.pone.0289960 37585411
    [Google Scholar]
  36. AliN.H. Al-KuraishyH.M. Al-GareebA.I. AlnaaimS.A. AlexiouA. PapadakisM. KhalifaA.A. SaadH.M. BatihaG.E.S. Neprilysin inhibitors and risk of Alzheimer’s disease: A future perspective.J. Cell. Mol. Med.2024282e1799310.1111/jcmm.17993 37847125
    [Google Scholar]
  37. WangX. SongR. LiZ. Salviolone protects against high glucose‐induced proliferation, oxidative stress, inflammation, and fibrosis of human renal mesangial cells by upregulating membrane metalloendopeptidase expression.Chem. Biol. Drug Des.2023101481982810.1111/cbdd.14183 36404132
    [Google Scholar]
  38. LiuY. LuC.Y. ZhengY. ZhangY.M. QianL.L. LiK.L. TseG. WangR.X. LiuT. Role of angiotensin receptor-neprilysin inhibitor in diabetic complications.World J. Diabetes202415586787510.4239/wjd.v15.i5.867 38766431
    [Google Scholar]
  39. KjeldsenS.A.S. GluudL.L. WergeM.P. PedersenJ.S. BendtsenF. AlexiadouK. TanT. TorekovS.S. IepsenE.W. JensenN.J. RichterM.M. GoetzeJ.P. RungbyJ. HartmannB. HolstJ.J. HolstB. HoltJ. GustafssonF. MadsbadS. SvaneM.S. Bojsen-MøllerK.N. Wewer AlbrechtsenN.J. Neprilysin activity is increased in metabolic dysfunction-associated steatotic liver disease and normalizes after bariatric surgery or GLP-1 therapy.iScience2023261110819010.1016/j.isci.2023.108190 37953952
    [Google Scholar]
/content/journals/emiddt/10.2174/0118715303331820240820072804
Loading
/content/journals/emiddt/10.2174/0118715303331820240820072804
Loading

Data & Media loading...

Supplements

Supplementary material, along with the published article, is available on the publisher's website.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test