The effects of Type 1 diabetes on colon smooth muscle

Abstract

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 Ca2+ increase, as measured by ratiometric imaging of fura-2 fluorescence of colonic SM strips. This attenuated Ca2+ 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 Ca2+levels. Western blotting and qRT-PCR analysis revealed significant changes in Ca2+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 Ca2+ handling. NIH RO1 DK61130