Microcirculation and Insulin Resistance

Post-Myocardial Infarction Insulin Resistance: A Sentinel Role for the Muscle Microcirculation

Author(s): David C. Poole and Timothy I. Musch

Pp: 107-118 (12)

DOI: 10.2174/978160805057410901010107

* (Excluding Mailing and Handling)

Abstract

Patients who have suffered a myocardial infarction (MI) and live with chronic heart failure (CHF) exhibit a substantial reduction in peripheral insulin sensitivity and increase their risk for developing diabetes by several-fold. To establish the putative role for post-myocardial infarction (MI) microcirculatory dysfunction in insulin resistance several questions must be addressed. Paramount amongst these are: 1. What are the microcirculatory hemodynamic characteristics in healthy resting muscle? 2. How are these impacted in post-infarction CHF? 3. Can current models of bloodtissue substrate delivery/exchange support a role for CHF-induced functional alterations in insulin resistance? This brief review considers that skeletal muscle, in part because of its great mass, prodigious capillarity and metabolic plasticity, constitutes a primary organ in body glucose homeostasis. The myriad changes in arteriolar vasoregulation post-MI, whilst certainly important with respect to the control of bulk muscle blood flow and its distribution, will not be addressed in depth herein. Rather, the questions posed above will be focussed within the context of recent novel observations at the capillary level i.e., at the primary site of blood-muscle exchange. These observations challenge the dogma that, in resting muscle, most capillaries are not recruited at rest which, if correct, would restrict their participation in glucose uptake and homeostasis. This is a crucial issue because direct observations suggest that, in healthy muscle, most capillaries do support continuous red blood cell (RBC) flux. In contrast, in post-MI CHF, a substantial proportion of skeletal muscle capillaries cease to support RBC flux both at rest and during contractions and it is likely that this constitutes a sentinel event in insulin resistance. Development and optimization of treatment strategies designed to ameliorate insulin resistance and halt or reverse the progression towards overt diabetes in CHF patients are dependent upon resolving these issues.

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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 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 <= 873336012 and j.to_ip >=873336012 )) and ((j.from_date <= 1740497167 and j.to_date >= 1740497167 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1916) 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 <= 873336012 and j.to_ip >=873336012 )) and ((j.from_date <= 1740497167 and j.to_date >= 1740497167 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1916) 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 <= 873336012 and j.to_ip >=873336012 )) and ((j.from_date <= 1740497167 and j.to_date >= 1740497167 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1916)
      930μsalphaeurekaselec_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` = 924 and `b`.`banner_from_date` <= 1740497167 and `b`.`banner_to_date` >= 1740497167 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.09msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 924
      • 3: 1740497167
      • 4: 1740497167
      • 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='1c59e6e2710ba69507ab15c94a665423'
      240μsalphaeurekaselec_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\Chapter
    1Chapter.php#?
    App\Models\Keywords
    1Keywords.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        0Jnfsf6HzpRnvKd0n5Spis4U4MdfZbO2IwLFtKQb
        uc_cart_id
        1c59e6e2710ba69507ab15c94a665423
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1916" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/1916
        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:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6IkhhaVBGTnpqRENCVmNtY28zSEdGRFE9PSIsInZhbHVlIjoibHQrcXphcTFjbG5UNjlzaWZEOXpic0QrN09XaVFjejBHLzNqT1lNVThURT0iLCJtYWMiOiI5YmJkZmU4MTkxYjBmNmYwODAyYzk3MDE0OWZkNDYzMTliYTk2YjZhOTVmYzgwYzgxMmMwYzI5ZDhjNTM2YTZhIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6IkhhaVBGTnpqRENCVmNtY28zSEdGRFE9PSIsInZhbHVlIjoibHQrcXphcTFjbG5UNjlzaWZEOXpic0QrN09XaVFjejBHLzNqT1lNVThURT0iLCJtYWMiOiI5YmJkZmU4MTkxYjBm" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "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" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        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 15:26:07 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjNHbytXN255VDczQXN3aUFUeDN3TFE9PSIsInZhbHVlIjoiTTQzWE5velJjSUpxcW5ZM3gzQWlhOGZPMndFYVlKS21WcXo3c1VaYnRmNjNrNklaUU4yQVdxVTRRWU52OVZSMEVWanhoSXBUZmtLSnZpOUFaZ1JodW0xU21VQ29jYUdGR2Z0ZGdkczZRaGVaNkZhQWJwbVVLcFdhNjJIc0d4YzkiLCJtYWMiOiI2OWM1ZWE5NWJjNzE2ZjNiYzZjMzMxZmUzMTc4ZjlmNGMwMWU2NWExYzdkYWI1YjllNmFjNWJiMTg3NzU2MDIyIiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 03:26:07 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IjNHbytXN255VDczQXN3aUFUeDN3TFE9PSIsInZhbHVlIjoiTTQzWE5velJjSUpxcW5ZM3gzQWlhOGZPMndFYVlKS21WcXo3c1VaYnRmNjNrNklaUU4yQVdxVTRRWU52OVZSMEVWanhoS" 1 => "alphaeurekaselectnet_session=eyJpdiI6Inhic1p2OHlBd1VGTVA4OThMRnRzRnc9PSIsInZhbHVlIjoiS1FHdjR1V2R4d2tFcWNNR3VaSFdrZFJMZ1pFWXd3REp1WU9pTUNDTVpzVWtqUXFjenJIMmdQZXJlL3diSVd1ODVYbHFIU2MzajE1bTVxdWxUUTRWcU5OcTZRcVNDbTNTaE9YNXhTTnVSQ085T1NaNGdINDlsU0N5V25VYzBDMGciLCJtYWMiOiJiMTIzYjZlY2Y0MWViNTI5NjVlMjg3ZGM4MTgyYzliMzJlOWE5MDM1YTljYmU3MjczZWVjZjU5N2NkMmM0YjBhIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6Inhic1p2OHlBd1VGTVA4OThMRnRzRnc9PSIsInZhbHVlIjoiS1FHdjR1V2R4d2tFcWNNR3VaSFdrZFJMZ1pFWXd3REp1WU9pTUNDTVpzVWtqUXFjenJIMmdQZXJ" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjNHbytXN255VDczQXN3aUFUeDN3TFE9PSIsInZhbHVlIjoiTTQzWE5velJjSUpxcW5ZM3gzQWlhOGZPMndFYVlKS21WcXo3c1VaYnRmNjNrNklaUU4yQVdxVTRRWU52OVZSMEVWanhoSXBUZmtLSnZpOUFaZ1JodW0xU21VQ29jYUdGR2Z0ZGdkczZRaGVaNkZhQWJwbVVLcFdhNjJIc0d4YzkiLCJtYWMiOiI2OWM1ZWE5NWJjNzE2ZjNiYzZjMzMxZmUzMTc4ZjlmNGMwMWU2NWExYzdkYWI1YjllNmFjNWJiMTg3NzU2MDIyIiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 03:26:07 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IjNHbytXN255VDczQXN3aUFUeDN3TFE9PSIsInZhbHVlIjoiTTQzWE5velJjSUpxcW5ZM3gzQWlhOGZPMndFYVlKS21WcXo3c1VaYnRmNjNrNklaUU4yQVdxVTRRWU52OVZSMEVWanhoS" 1 => "alphaeurekaselectnet_session=eyJpdiI6Inhic1p2OHlBd1VGTVA4OThMRnRzRnc9PSIsInZhbHVlIjoiS1FHdjR1V2R4d2tFcWNNR3VaSFdrZFJMZ1pFWXd3REp1WU9pTUNDTVpzVWtqUXFjenJIMmdQZXJlL3diSVd1ODVYbHFIU2MzajE1bTVxdWxUUTRWcU5OcTZRcVNDbTNTaE9YNXhTTnVSQ085T1NaNGdINDlsU0N5V25VYzBDMGciLCJtYWMiOiJiMTIzYjZlY2Y0MWViNTI5NjVlMjg3ZGM4MTgyYzliMzJlOWE5MDM1YTljYmU3MjczZWVjZjU5N2NkMmM0YjBhIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6Inhic1p2OHlBd1VGTVA4OThMRnRzRnc9PSIsInZhbHVlIjoiS1FHdjR1V2R4d2tFcWNNR3VaSFdrZFJMZ1pFWXd3REp1WU9pTUNDTVpzVWtqUXFjenJIMmdQZXJ" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "0Jnfsf6HzpRnvKd0n5Spis4U4MdfZbO2IwLFtKQb" "uc_cart_id" => "1c59e6e2710ba69507ab15c94a665423" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1916" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 15:26:07GET/chapter/1916112193