Abstract
A novel glycogen phosphorylase inhibitor FR258900 was isolated from the cultured broth of a fungal strain No. 138354. We examined the hypoglycemic effects of FR258900 in diabetic animal models. FR258900 treatment significantly reduced the plasma glucose concentrations during oral glucose tolerance tests in diabetic mice models, including db/db mice and STZ-induced diabetic mice. Furthermore, FR258900 treatment resulted in rapid decrease in the plasma glucose levels in db/db mice. These improvements in glucose disposal were accompanied by increased liver glycogen contents, suggesting that the glucose lowering effects of FR258900 were attributed to suppressed hepatic glycogen breakdown and increased hepatic glycogen synthesis. Taken together, our results suggest that glycogen phosphorylase is a potentially useful target in new therapies against diabetes.
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Furukawa S, Tsurumi Y, Murakami K, Nakanishi T, Ohsumi K, Hashimoto M, Nishikawa M, Takase S, Nakayama O, Hino M . FR258900, a novel glycogen phosphorylase inhibitor isolated from fungus No. 138354. I. Taxonomy, fermentation, isolation and biological activities. J Antibiot 58: 497–502 ( 2005)
Treadway JL, Mendys P, Hoover DJ . Glycogen phosphorylase inhibitors for treatment of type 2 diabetes mellitus. Exp Opin Invest Drugs 10: 439–454 ( 2001)
Ohtsu Y, Sasamura H, Shibata T, Nakajima H, Hino M, Fujii T . The novel gluconeogenesis inhibitor FR225659 and related compounds that originate from Helicomyces sp. No. 19353. II. Biological profiles. J Antibiot 56: 689–693 ( 2003)
Gómez-Lechón MJ, Ponsoda X, Castell JV . A microassay for measuring glycogen in 96-well-cultured cells. Anal Biochem 236: 296–301 ( 1996)
Consoli A . Role of liver in pathophysiology of NIDDM. Diabetes Care 15: 430–441 ( 1992)
Barrett EJ, Liu Z . Hepatic glucose metabolism and insulin resistance in NIDDM and obesity. Baillieres Clin Endocrinol Metab 7: 875–901 ( 1993)
Diraison F, Large V, Brunengraber H, Beylot M . Non-invasive tracing of liver intermediary metabolism in normal subjects and in moderately hyperglycaemic NIDDM subjects. Evidence against increased gluconeogenesis and hepatic fatty acid oxidation in NIDDM. Diabetologia 41: 212–220 ( 1998)
Hellerstein MK, Neese RA, Linfoot P, Christiansen M, Turner S, Letscher A . Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study. J Clin Invest 100: 1305–1319 ( 1997)
Martin WH, Hoover DJ, Armento SJ, Stock IA, McPherson RK, Danley DE, Stevenson RW, Barrett EJ, Treadway JL . Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo. Proc Natl Acad Sci USA 95: 1776–1781 ( 1998)
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Furukawa, S., Murakami, K., Nishikawa, M. et al. FR258900, a Novel Glycogen Phosphorylase Inhibitor Isolated from Fungus No. 138354. J Antibiot 58, 503–506 (2005). https://doi.org/10.1038/ja.2005.67
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DOI: https://doi.org/10.1038/ja.2005.67
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