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Altered calcium signaling in colonic smooth muscle of type 1 diabetic mice

Altered calcium signaling in colonic smooth muscle of type 1 diabetic mice Abstract Seventy-six percent of diabetic patients develop gastrointestinal symptoms, such as constipation. However, the direct effects of diabetes on intestinal smooth muscle are poorly described. This study aimed to identify the role played by smooth muscle in mediating diabetes-induced colonic dysmotility. To induce type 1 diabetes, mice were injected intraperitoneally with low-dose streptozotocin once a day for 5 days. Animals developed hyperglycemia (>200 mg/dl) 1 wk after the last injection and were euthanized 7–8 wk after the last treatment. Computed tomography demonstrated decreased overall gastrointestinal motility in the diabetic mice. In vitro contractility of colonic smooth muscle rings from diabetic mice was also decreased. Fura-2 ratiometric Ca 2+ imaging showed attenuated Ca 2+ increases in response to KCl stimulation that were associated with decreased light chain phosphorylation in diabetic mice. The diabetic mice also exhibited elevated basal Ca 2+ levels, increased myosin phosphatase targeting subunit 1 expression, and significant changes in expression of Ca 2+ handling proteins, as determined by quantitative RT-PCR and Western blotting. Mice that were hyperglycemic for <1 wk also showed decreased colonic contractile responses that were associated with decreased Ca 2+ increases in response to KCl stimulation, although without an elevation in basal Ca 2+ levels or a significant change in the expression of Ca 2+ signaling molecules. These data demonstrate that type 1 diabetes is associated with decreased depolarization-induced Ca 2+ influx in colonic smooth muscle that leads to attenuated myosin light chain phosphorylation and impaired colonic contractility. streptozotocin colon voltage-gated calcium channel Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print October 2011 , doi: 10.​1152/​ajpgi.​00183.​2011 AJP - GI January 2012 vol. 302 no. 1 G66-G76 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpgi.00183.2011v1 302/1/G66 most recent Classifications Neuroregulation and Motility Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Touw, K. Articles by Herring, B. P. PubMed PubMed citation Articles by Touw, K. Articles by Herring, B. P. Related Content Load related web page information Current Issue January 2012, 302 (1) Alert me to new issues of AJP - GI About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2011 the American Physiological Society Print ISSN: 0193-1857 Online ISSN: 1522-1547 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview(); http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Gastrointestinal and Liver Physiology The American Physiological Society

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1857
eISSN
1522-1547
DOI
10.1152/ajpgi.00183.2011
pmid
21979758
Publisher site
See Article on Publisher Site

Abstract

Abstract Seventy-six percent of diabetic patients develop gastrointestinal symptoms, such as constipation. However, the direct effects of diabetes on intestinal smooth muscle are poorly described. This study aimed to identify the role played by smooth muscle in mediating diabetes-induced colonic dysmotility. To induce type 1 diabetes, mice were injected intraperitoneally with low-dose streptozotocin once a day for 5 days. Animals developed hyperglycemia (>200 mg/dl) 1 wk after the last injection and were euthanized 7–8 wk after the last treatment. Computed tomography demonstrated decreased overall gastrointestinal motility in the diabetic mice. In vitro contractility of colonic smooth muscle rings from diabetic mice was also decreased. Fura-2 ratiometric Ca 2+ imaging showed attenuated Ca 2+ increases in response to KCl stimulation that were associated with decreased light chain phosphorylation in diabetic mice. The diabetic mice also exhibited elevated basal Ca 2+ levels, increased myosin phosphatase targeting subunit 1 expression, and significant changes in expression of Ca 2+ handling proteins, as determined by quantitative RT-PCR and Western blotting. Mice that were hyperglycemic for <1 wk also showed decreased colonic contractile responses that were associated with decreased Ca 2+ increases in response to KCl stimulation, although without an elevation in basal Ca 2+ levels or a significant change in the expression of Ca 2+ signaling molecules. These data demonstrate that type 1 diabetes is associated with decreased depolarization-induced Ca 2+ influx in colonic smooth muscle that leads to attenuated myosin light chain phosphorylation and impaired colonic contractility. streptozotocin colon voltage-gated calcium channel Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print October 2011 , doi: 10.​1152/​ajpgi.​00183.​2011 AJP - GI January 2012 vol. 302 no. 1 G66-G76 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpgi.00183.2011v1 302/1/G66 most recent Classifications Neuroregulation and Motility Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Touw, K. Articles by Herring, B. P. PubMed PubMed citation Articles by Touw, K. Articles by Herring, B. P. Related Content Load related web page information Current Issue January 2012, 302 (1) Alert me to new issues of AJP - GI About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2011 the American Physiological Society Print ISSN: 0193-1857 Online ISSN: 1522-1547 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

Journal

AJP - Gastrointestinal and Liver PhysiologyThe American Physiological Society

Published: Jan 1, 2012

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