Tetrahydrobiopterin Has a Glucose-Lowering Effect by Suppressing Hepatic Gluconeogenesis in an Endothelial Nitric Oxide Synthase―Dependent Manner in Diabetic Mice

• Published in: Diabetes (New York, N.Y.) Vol. 62; no. 9; pp. 3033 - 3043
• Main Authors: ABUDUKADIER, Abulizi, FUJITA, Yoshihito, HASEGAWA, Hiroyuki, INAGAKI, Nobuya, OBARA, Akio, OHASHI, Akiko, FUKUSHIMA, Toru, SATO, Yuichi, OGURA, Masahito, NAKAMURA, Yasuhiko, FUJIMOTO, Shimpei, HOSOKAWA, Masaya
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.09.2013
• Subjects: Animals; Biological and medical sciences; Biopterins - analogs & derivatives; Biopterins - therapeutic use; Care and treatment; Cells, Cultured; Complications and side effects; Diabetes; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - enzymology; Diabetes Mellitus, Experimental - metabolism; Diabetes. Impaired glucose tolerance; Dosage and administration; Effects; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Enzymes; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Genetic aspects; Gluconeogenesis; Gluconeogenesis - drug effects; Gluconeogenesis - genetics; Glucose; Hepatocytes - drug effects; Hepatocytes - metabolism; Hypoglycemic agents; Hypoglycemic Agents - therapeutic use; Immunoblotting; Immunohistochemistry; Insulin resistance; Liver - drug effects; Liver - metabolism; Male; Medical sciences; Mice; Mice, Inbred C57BL; Nitric oxide; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Original Research; Physiological aspects; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Rodents; Type 2 diabetes; Japan; Endocrinopathy; Enzyme; Diabetes mellitus; Rodentia; Glucose; Nitric-oxide synthase; Endothelium; Vertebrata; Mammalia; Mouse; Tetrahydrobiopterin; Blood vessel; Animal; Circulatory system; Oxidoreductases; Gluconeogenesis

Endothelial nitric oxide synthase (eNOS) dysfunction induces insulin resistance and glucose intolerance. Tetrahydrobiopterin (BH4) is an essential cofactor of eNOS that regulates eNOS activity. In the diabetic state, BH4 is oxidized to 7,8-dihydrobiopterin, which leads to eNOS dysfunction owing to e...