Gastrointestinal dysfunction in diabetic rats relates with a decline in tissue l-arginine content and consequent low levels of nitric oxide

Abstract

Diabetic subjects exhibit low levels of nitric oxide (NO), its precursor l-arginine, and nitric oxide synthase (NOS) in tissues like endothelium and kidney. In view of this, we speculated that gastrointestinal (GI) dysfunction in diabetes could be related to similar changes in NO turnover in GI tissues. Hence, the studies were carried out in rats after eight weeks of streptozotocin-induced hyperglycemia, wherein the GI functions were assessed in terms of gastric emptying and intestinal transit using barium sulfate semisolid test meal, and the levels of l-arginine and NO in pylorus and ileum were estimated, respectively, by HPLC and amperometry. The results revealed that diabetic group exhibited significant delay in gastric emptying and intestinal transit, and the pylorus and ileum tissues had significantly low levels of NO and l-arginine. Daily treatment of non-diabetic rats with NOS inhibitor [ Nω-nitro- l-arginine methyl ester (10 mg/kg/day, p.o.)] for eight weeks produced similar delay in gastric emptying and intestinal transit with associated low levels of NO in GI tissues. Daily supplementation of l-arginine (100 mg/kg, p.o.) for eight weeks to diabetic and NOS inhibitor treated non-diabetic group was found to restore the gastric emptying and intestinal transit and improved the levels of NO in GI tissues. The findings indicate that diabetes-induced l-arginine deficiency and consequent low levels of NO in GI tissues could be possible cause for the GI dysfunction, and l-arginine supplementation can prevent the same. However, extensive clinical investigations are necessary to recommend the use of l-arginine for the treatment of GI dysfunctions in diabetes.