Frontiers in Medicinal Chemistry

Volume: 9

Dipeptidyl Peptidase-4 (CD26): Knowing the Function before Inhibiting the Enzyme

Author(s): Elena Matteucci and Ottavio Giampietro

Pp: 80-102 (23)

DOI: 10.2174/9781681082493116090005

* (Excluding Mailing and Handling)

Abstract

Dipeptidyl peptidase-4 (DPP4) or adenosine deaminase complexing protein 2 (ADCP 2) or T-cell activation antigen CD26 (EC 3.4.14.5.) is a serine exopeptidase belonging to the S9B protein family that cleaves X-proline dipeptides from the N-terminus of polypeptides, such as chemokines, neuropeptides, and peptide hormones. The enzyme is a type II transmembrane glycoprotein, expressed on the surface of many cell types, whose physiological functions have begun to emerge in recent years. Protein dimerisation is required for catalytic activity and glycosylation of the enzyme could impact on its physiological functions. The dimeric glycoprotein ADCP has been found linked to adenosine deaminase (ADA) whose relationship with lymphocyte maturationdifferentiation is well established.

Since implicated in the regulation of the biological activity of hormones and chemokines, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, DPP4 inhibition offered a new potential therapeutic approach for type 2 diabetes mellitus as monotherapy and adjunct therapy to other oral agents. The clinical use of orally active inhibitors of DPP4 has been initially associated with side effects that have been in part attributed to the inhibition of related serine proteases, such as DPP8 and DPP9. Moreover, CD26 has a key role in immune regulation as a T cell activation molecule and in immune-mediated disorder; all-cause infections were found increased after sitagliptin treatment. So far, systematic reviews and meta-analysis on the efficacy and safety in human type 2 diabetes of orally active DPP4 inhibitors were published, but some questions remain open. Long-term evaluation of the risk-benefit ratio in controlled trials is still required, possibly through the use of multiple risk-benefit approaches across different indications and treatment populations. The review summarises present knowledge in the field and suggests some potential directions of future research.


Keywords: CD26, dipeptidyl peptidase-4, DPP4 inhibitors, serine peptidase, type 2 diabetes mellitus.

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      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314378200 and j.to_ip >=314378200 )) and ((j.from_date <= 1739848493 and j.to_date >= 1739848493 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 8736) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314378200 and j.to_ip >=314378200 )) and ((j.from_date <= 1739848493 and j.to_date >= 1739848493 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 8736) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314378200 and j.to_ip >=314378200 )) and ((j.from_date <= 1739848493 and j.to_date >= 1739848493 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 8736)
      1msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1925 and `b`.`banner_from_date` <= 1739848493 and `b`.`banner_to_date` >= 1739848493 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.5msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1925
      • 3: 1739848493
      • 4: 1739848493
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='acd1188a4f754867c86c85c9a6036d78'
      290μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    5Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
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        uc_cart_id
        acd1188a4f754867c86c85c9a6036d78
        _previous
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        _flash
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        PHPDEBUGBAR_STACK_DATA
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        path_info
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        status_code
        200
        
        status_text
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        format
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        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-18 03:14:53GET/chapter/8736112197