Characterization of the ileal muscarinic receptor system in 70-week-old type II Goto–Kakizaki diabetic rats; effects of cyclohexenonic long-chain fatty alcohol

Abstract

As gastrointestinal motility disorders are frequently reported in patients with diabetes, we attempted to clarify the effects of cyclohexenonic long-chain fatty alcohol in type 2 Goto-Kakizaki (GK) diabetic enteropathy. At 40 weeks of age male GK rats divided into three groups (treated with 0, 2 or 8 mg/kg of cyclohexenonic long-chain fatty alcohol; started at the age of 40 weeks). Age-matched male Wistar rats were used in this study. At 70 weeks of age the ileal functions were estimated by organ bath studies using 100 mM KCl and carbachol. The expression levels of muscarinic M(2) and M(3) receptor mRNAs in the ileum were investigated by real-time polymerase chain reaction (PCR). Treatment with cyclohexenonic long-chain fatty alcohol did not alter the diabetic status of the GK rats, i.e., body weight, serum glucose, and serum insulin levels, but significantly ameliorated diabetes-induced hypercontractility of the rat ileum caused by carbachol in a dose-dependent manner. Although there were no significant differences in the expression levels of muscarinic M(3) receptor mRNAs in any of the groups, cyclohexenonic long-chain fatty alcohol reversed the diabetes-induced up-regulation of intestinal muscarinic M(2) receptor mRNAs in treatment groups. These results indicate that cyclohexenonic long-chain fatty alcohol exerts its therapeutic effects on hypercontractility in the ileum of 70-week-old GK type 2 diabetic rats by ameliorating overexpression of muscarinic M(2) receptors.

Muscarinic receptors and their mRNAs in type 2 Goto‐Kakizaki diabetic rat prostate

“…The differences between previous results and our findings are probably due to different hormonal regulations between diabetes type 1 and type 2. The up‐regulation of muscarinic receptors in diabetes type 2 rat prostate was similar to the findings reported in type 2 diabetic rat bladder and ileum, and therefore they could share the same pathophysiological mechanisms 18, 21. On the other hand, the above effect of type 2 diabetes on muscarinic receptors in the prostate is quite different from the effect of STZ‐induced type 1 diabetes on prostate where a down‐regulation of the prostatic muscarinic receptors has been reported 18–21.…”