Pharmacological and Molecular Perspectives on Diabetes

Endocrine Role of Osteocalcin in Homeostatic Regulation of Glucose Metabolism

Author(s): Madhu Gupta*, Md. Arshad and Rahul Gupta

Pp: 38-53 (16)

DOI: 10.2174/9789815040227122010006

* (Excluding Mailing and Handling)

Abstract

 Osteocalcin, a well-known bone formation marker, is secreted from osteoblasts and exists in fully carboxylated, partially carboxylated, and completely uncarboxylated forms. The endocrine involvement of uncarboxylated osteocalcin in glucose homeostasis has recently been confirmed. It has been demonstrated that double recessive osteocalcin mutant mice are hyperglycemic, hypoinsulinemic, and have reduced β cell numbers and insulin resistance. In contrast, leptin (an adipocyte-derived hormone) indirectly regulates the secretion of insulin in part through inhibition of osteocalcin conversion to uncarboxylated form via β2 adrenergic receptor signaling in osteoblasts. Because uncarboxylated osteocalcin is a secretagogue of insulin, which in turn positively regulates the bone formation, osteocalcin lies at the centre of the complex mechanism of glucose homeostasis and bone remodeling network.


Keywords: β2 adrenergic receptor, Bone Gla Protein, Bone remodeling, GPRC6A, Glucose homeostasis, Hyperglycaemic, Insulin, Receptor tyrosine kinase, Leptin, Sympathetic tone, Uncarboxylated osteocalcin.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
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      • 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 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 <= 309701250 and j.to_ip >=309701250 )) and ((j.from_date <= 1740527114 and j.to_date >= 1740527114 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16955) 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 <= 309701250 and j.to_ip >=309701250 )) and ((j.from_date <= 1740527114 and j.to_date >= 1740527114 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16955) 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 <= 309701250 and j.to_ip >=309701250 )) and ((j.from_date <= 1740527114 and j.to_date >= 1740527114 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16955)
      580μsalphaeurekaselec_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` = 3343 and `b`.`banner_from_date` <= 1740527114 and `b`.`banner_to_date` >= 1740527114 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.03msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 3343
      • 3: 1740527114
      • 4: 1740527114
      • 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='8792be405c5f38e5a91d1cc186b4dceb'
      200μsalphaeurekaselec_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
    11Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        eZXNhp5xOyDYzV4W2pmmCBxjYMW3P8D92bmcfEue
        uc_cart_id
        8792be405c5f38e5a91d1cc186b4dceb
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/16955" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/16955
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 23:45:14 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkdzUTRYSzd3blVqeVhUaWJRNUVrb0E9PSIsInZhbHVlIjoiMnN4Z3ZFSG9MOXdZU09Iejc1SytaWVB4Y0tza0JId3htOXNNZHZucmpXRmxzUGNKbmltRlArV2RGNkg4WmtFVVQybUtDbnJrNmFkYkVmV0V5WExWT21zNVlsQmlFa3VDblJENVRHVmp1ekFZYVZKc243RThKc2hDbW50Zzl1dnUiLCJtYWMiOiI2MzdhZDA1NDgwOWVjZDQ0MjlmMGZlZWY5MWM1OWIzMzJlYjMyNTNhZmY3YjVhMWQ1Nzc2NzU5YzUxY2VkOTExIiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 11:45:14 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IkdzUTRYSzd3blVqeVhUaWJRNUVrb0E9PSIsInZhbHVlIjoiMnN4Z3ZFSG9MOXdZU09Iejc1SytaWVB4Y0tza0JId3htOXNNZHZucmpXRmxzUGNKbmltRlArV2RGNkg4WmtFVVQybUtDb" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImRDNzFZOTZSQ01EYTNlOG9wVFhMUHc9PSIsInZhbHVlIjoiUGI4TkdDRk1vb2hidjZQS2ZUS290cGIxNTVZUm5TeHd5UTJoYzczanBkSFVueUpCczBlRDZnMnRwMEx0UEFITWJoSGlKcGtmTmwzS3g3c1QrTnVUUm5NaTcrQklIWFljNVo3dTNrV0FLd3lQdGhnT09zR2lCVTczVEluNnlraXYiLCJtYWMiOiI4NTA4ZGVmYWQ2ZjY4ZTkyMTExYTM2N2M0ZWE0YTIxYjI4YmJmZjkwYzM1MGU2OGI0NWFiYTk0MTFkZGNkNjBkIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImRDNzFZOTZSQ01EYTNlOG9wVFhMUHc9PSIsInZhbHVlIjoiUGI4TkdDRk1vb2hidjZQS2ZUS290cGIxNTVZUm5TeHd5UTJoYzczanBkSFVueUpCczBlRDZnMnR" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkdzUTRYSzd3blVqeVhUaWJRNUVrb0E9PSIsInZhbHVlIjoiMnN4Z3ZFSG9MOXdZU09Iejc1SytaWVB4Y0tza0JId3htOXNNZHZucmpXRmxzUGNKbmltRlArV2RGNkg4WmtFVVQybUtDbnJrNmFkYkVmV0V5WExWT21zNVlsQmlFa3VDblJENVRHVmp1ekFZYVZKc243RThKc2hDbW50Zzl1dnUiLCJtYWMiOiI2MzdhZDA1NDgwOWVjZDQ0MjlmMGZlZWY5MWM1OWIzMzJlYjMyNTNhZmY3YjVhMWQ1Nzc2NzU5YzUxY2VkOTExIiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 11:45:14 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IkdzUTRYSzd3blVqeVhUaWJRNUVrb0E9PSIsInZhbHVlIjoiMnN4Z3ZFSG9MOXdZU09Iejc1SytaWVB4Y0tza0JId3htOXNNZHZucmpXRmxzUGNKbmltRlArV2RGNkg4WmtFVVQybUtDb" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImRDNzFZOTZSQ01EYTNlOG9wVFhMUHc9PSIsInZhbHVlIjoiUGI4TkdDRk1vb2hidjZQS2ZUS290cGIxNTVZUm5TeHd5UTJoYzczanBkSFVueUpCczBlRDZnMnRwMEx0UEFITWJoSGlKcGtmTmwzS3g3c1QrTnVUUm5NaTcrQklIWFljNVo3dTNrV0FLd3lQdGhnT09zR2lCVTczVEluNnlraXYiLCJtYWMiOiI4NTA4ZGVmYWQ2ZjY4ZTkyMTExYTM2N2M0ZWE0YTIxYjI4YmJmZjkwYzM1MGU2OGI0NWFiYTk0MTFkZGNkNjBkIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImRDNzFZOTZSQ01EYTNlOG9wVFhMUHc9PSIsInZhbHVlIjoiUGI4TkdDRk1vb2hidjZQS2ZUS290cGIxNTVZUm5TeHd5UTJoYzczanBkSFVueUpCczBlRDZnMnR" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "eZXNhp5xOyDYzV4W2pmmCBxjYMW3P8D92bmcfEue" "uc_cart_id" => "8792be405c5f38e5a91d1cc186b4dceb" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/16955" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 23:45:14GET/chapter/169551121913