N-hexacosanol reverses diabetic induced muscarinic hypercontractility of ileum in the rat

• Published in: European journal of pharmacology 2006-09, Vol.545 (2), p.177-184
• Main Authors: Shinbori, Chiko, Saito, Motoaki, Kinoshita, Yukako, Satoh, Itaru, Kono, Tomoharu, Hanada, Takuya, Nanba, Eiji, Adachi, Kaori, Suzuki, Hiroto, Yamada, Masashi, Satoh, Keisuke
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Cyclohexenonic long-chain fatty alcohol; Diabetes; Diabetes Mellitus, Experimental - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic Neuropathies - drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty Alcohols - pharmacology; Fatty Alcohols - therapeutic use; Ileum - drug effects; Ileum - physiopathology; Male; Medical sciences; mRNA; Muscarinic M 2 receptor; Muscarinic M 3 receptor; Muscle Contraction - drug effects; Neuropathy; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Receptor, Muscarinic M2 - drug effects; Receptor, Muscarinic M2 - genetics; Receptor, Muscarinic M3 - drug effects; Receptor, Muscarinic M3 - genetics; Streptozocin
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.06.043

Diabetic neuropathy, a major complication of diabetes mellitus, is associated with development of gastrointestinal motility dysfunction and autonomic neuropathy. N-hexacosanol has neurotrophic effects and exhibits a wide variety of biological actions. In this study, we investigated the effects of cyclohexenonic long-chain fatty alcohol ( N-hexacosanol) on streptozotocin-diabetic hypercontractility in the rat ileum longitudinal muscles. Treatment with N-hexacosanol did not alter the diabetic status of the animals, i.e., body weight, serum glucose, and serum insulin levels, but significantly restored the thickness of intestine wall and ameliorated diabetes-induced hypercontractility of the rat ileum in a dose-dependent manner. Furthermore, N-hexacosanol reversed the diabetes-induced upregulation of intestinal muscarinic M 2 and M 3 receptors mRNAs in the streptozotocin-diabetic rats. These results indicate that N-hexacosanol has therapeutic effects on hypercontractility in the diabetic ileum by ameliorating overexpression of muscarinic M 2 and M 3 receptors mRNAs.