| Objective:To observe the changes of gastric motility in rat models with diabetes mellitus(DM), and to study the effects of sepiapterin (SEP) on gastric emptying and nitrergic system in female diabetic rats.Methods:A rat model of DM was created by intraperitoneal injection of streptozotocin (STZ). Gastric nitrergic relaxation in the presence or absence of high glucose and SEP were measured by electric field stimulation. Nitric oxide release was measured colorimetrically by NO assay kit. The expression of nNOSa and dimerization was detected by Western blot.Results:A significant weight loss was noted in the diabetic rats compared to control group (t=2.45,p<0.05). Fasting blood glucose levels were significantly elevated in female rats after diabetes induction(t=11.05, p<0.01).Weight(t=0.28,t=0.92,P>0.05) and blood glucose levels (t=0.87,t=0.79,P>0.05) were unchanged upon supplementation of SEP10days in both control and in diabetic female rats.A significant reduction in the solid gastric emptying was observed in diabetic rats compared to control(t=7.39,p<0.01).SEP supplementation did not affect the solid gastric emptying in control rats(t=0.26, P=0.80), whereas, a significant induction (t=7.08,p<0.01) in the solid gastric emptying was observed when diabetic animals were supplemented with SEP. Induction of diabetes caused a decrease(t=9.71.p<0.01) in the nitrergic relaxation compared with control rats. Supplementation of SEP resulted in almost complete reversal(t=6.65,p<0.01) of diabetes-induced alteration of nitrergic relaxation. MTX treatment4days significantly decreased the nitrergic relaxation in all areas of gastric muscular tissues(fundus:t=2.36,p<0.05; antrum:t=2.36, p<0.05; pylorus:t=2.36,p<0.05).MTX exposure caused a significant decrease(t=3.73, P<0.01) in NO release in vitro.MTX-induced decrease in NO release was attenuated by SEP treatment (t=2.59, P<0.05). The protein level of nNOS a in gastric antrum tissue was significantly decreased(t=2.26, p<0.05)following9weeks of diabetes. Supplementation of SEP to diabetic female rats results in significant restoration of nNOS a protein level (t=5.65, p<0.01).Conclusions:The above data suggests that supplementation of SEP accelerated gastric emptying and attenuated reduced gastric nNOSa expression, and dimerization. Therefore, SEP supplementation is a potential therapeutic option for female patients of diabetic gastroparesis. |
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