{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:12:45Z","timestamp":1785129165942,"version":"3.55.0"},"reference-count":42,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:p>Gastroparesis is a debilitating disease predominantly affecting young women. Recently, dysregulation of neuronal nitric oxide synthase (nNOS) in myenteric plexus neurons has been implicated for delayed solid gastric emptying\/gastroparesis in diabetic patients. In this study, we have explored the role of tetrahydrobiopterin (BH4), a major cofactor for nNOS activity and NO synthesis in diabetic gastroparesis. Diabetes was induced with single injection of streptozotocin (55 mg\/kg body wt, ip) in female rats, with experiments performed on week 3 or 9 following induction, with or without 3-wk BH4 supplementation. Gastric pyloric BH4 levels were significantly decreased in diabetic female rats compared with control (18.6 \u00b1 1.45 vs. 31.0 \u00b1 2.31 pmol\/mg protein). In vitro studies showed that 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of BH4 synthesis, significantly decreased gastric NO release and nitrergic relaxation. Three-week dietary supplementation of BH4 either from day 1 or week 6 significantly attenuated diabetes-induced delayed gastric emptying for solids (3 wk: BH4, 67 \u00b1 6.7 vs. diabetic, 36.05 \u00b1 7.09; 9 wk: BH4, 57 \u00b1 8.45 vs. diabetic, 33 \u00b1 9.91) and diabetes-induced reduction in pyloric nNOS-\u03b1 protein expression in female rats. Supplementation of BH4 significantly restored gastric nNOS-\u03b1 dimerization in 9-wk-old diabetic female rats. In addition, BH4 treatment reversed (17.23 \u00b1 5.81 vs. 42.0 \u00b1 2.70 mmHg \u00d7 s) the diabetes-induced changes in intragastric pressures (IGP) and gastric pyloric nitrergic relaxation (\u22120.62 \u00b1 0.01 vs. \u22120.22 \u00b1 0.07). BH4 deficiency plays a critical role in diabetes-induced alterations including delayed solid gastric emptying, increased IGP, reduced pyloric nitrergic relaxation, and nNOS-\u03b1 expression in female rats. Supplementation of BH4 accelerates gastric emptying by restoring nitrergic system in diabetic female rats. Therefore, BH4 supplementation is a potential therapeutic option for female patients of diabetic gastroparesis.<\/jats:p>","DOI":"10.1152\/ajpgi.00450.2009","type":"journal-article","created":{"date-parts":[[2010,2,26]],"date-time":"2010-02-26T03:18:19Z","timestamp":1267154299000},"page":"G692-G699","source":"Crossref","is-referenced-by-count":43,"title":["Tetrahydrobiopterin (BH4), a cofactor for nNOS, restores gastric emptying and nNOS expression in female diabetic rats"],"prefix":"10.1152","volume":"298","author":[{"given":"Pandu R. 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