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The effects of Type 1 diabetes on colon smooth muscle
Author(s) -
Touw Ketrija,
Chakraborty Saikat,
Zhang Wenwu,
Tune Johnathan,
Obukhov Alexander,
Gunst Susan,
Herring Paul
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1123.1
Subject(s) - contractility , myograph , medicine , motility , endocrinology , diabetes mellitus , contraction (grammar) , streptozotocin , type 2 diabetes , myosin light chain kinase , myosin , chemistry , biology , biochemistry , microbiology and biotechnology
Approximately 76% of diabetic patients develop gastrointestinal (GI) symptoms such as constipation. Our study investigated the effects of diabetes on smooth muscle (SM) of the GI tract. Mice were treated with low‐dose streptozotocin once a day for 5 days to induce hyperglycemia (>200 mg/dl). Colon motility was examined by CT scan after 7 weeks of hyperglycemia and revealed decreased overall GI tract motility. To directly measure the contractility of colonic SM, colons were dissected, cut into circular rings, hung in a myograph and contraction was elicited by KCl‐induced depolarization. In short term (1 week) and long term (7 weeks) diabetic mice there was decreased colon SM contractility that was associated with an attenuated Ca 2+ increase, as measured by ratiometric imaging of fura‐2 fluorescence of colonic SM strips. This attenuated Ca 2+ increase resulted in decreased myosin light chain phosphorylation thus explaining the decreased contractility of the colon. Long term diabetes was also associated with increased basal Ca 2+ levels. Western blotting and qRT‐PCR analysis revealed significant changes in Ca 2+ handling protein and mRNA levels following 7 weeks of hyperglycemia. After 1 week of hyperglycemia we also observed attenuated expression of Cav1.2b, SERCA2b and PMCA4. These results suggest that type 1 diabetes in mice leads to decreased colon motility in part due to altered Ca 2+ handling. NIH RO1 DK61130