Abstract
FR258900 is a novel glycogen synthesis activator produced by Fungus No. 138354. This compound was isolated from the culture broth by solvent extraction and reverse-phase column chromatography. FR258900 stimulated glycogen synthesis and glycogen synthase activity in primary rat hepatocytes. FR258900 exhibited a potent inhibitory effect on the activity of liver glycogen phosphorylase, suggesting that this compound may activate hepatic glycogen synthesis via glycogen phosphorylase inhibition. Thus, this glycogen phosphorylase inhibitor may be useful in the treatment of postprandial hyperglycemia in type 2 diabetes.
Similar content being viewed by others
Article PDF
References
DeFronzo RA, Bonadonna RC, Ferrannini E . Pathogenesis of NIDDM. A balanced overview. Diabetes Care 15: 318–368 ( 1992)
Consoli A . Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM. Diabetes Care 15: 430–441 ( 1992)
Nakase T . JCM Catalogue of Strains, 6th ed. RIKEN, Japan ( 1995)
Kornerup A, Wanscher JH . Methuen Handbook of Colour, 3rd ed. Methuen, London ( 1978)
Seglen PO . Preparation of isolated rat liver cells. Methods Cell Biol 13: 29–83 ( 1976)
Gómez-Lechón MJ, Ponsoda X, Castell JV . A microassay for measuring glycogen in 96-well-cultured cells. Anal Biochem 236: 296–301 ( 1996)
Coghlan MP, Culbert AA, Cross DA, Corcoran SL, Yates JW, Pearce NJ, Rausch OL, Murphy GJ, Carter PS, Roxbee Cox L, Mills D, Brown MJ, Haigh D, Ward RW, Smith DG, Murray KJ, Reith AD, Holder JC . Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol 7: 793–803 ( 2000)
Coats WS, Browner MF, Fletterick RF, Newgard CB . An engineered liver glycogen phosphorylase with AMP allosteric activation. J Biol Chem 266: 16113–16119 ( 1991)
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)
Swanson MA . Glucose-6-phosphatase from liver. Methods Enzymol 2: 541–543 ( 1955)
Radziuk J, Pye S . Hepatic glucose uptake, gluconeogenesis and the regulation of glycogen synthesis. Diabetes Metab Res Rev 17: 250–272 ( 2001)
Cohen P, Goedert M . GSK3 inhibitors: Development and therapeutic potential. Nat Rev Drug Discov 3: 479–487 ( 2004)
Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL, Normandin D, Cheng A, Himms-Hagen J, Chan CC, Ramachandran C, Gresser MJ, Tremblay ML, Kennedy BP . Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 283: 1544–1548 ( 1999)
Bollen M, Keppens S, Stalmans W . Specific features of glycogen metabolism in the liver. Biochem J 336: 19–31 ( 1998)
Aiston S, Hampson L, Gómez-Foix AM, Guinovart JJ, Agius L . Hepatic glycogen synthesis is highly sensitive to phosphorylase activity. J Biol Chem 276: 23858–23866 ( 2001)
Fosgerau K, Westergaard N, Quistorff B, Grunnet N, Kristiansen M, Lundgren K . Kinetic and functional characterization of 1,4-dideoxy-1,4-imino-D-arabinitol: A potent inhibitor of glycogen phosphorylase with anti-hyperglyceamic effect in ob/ob mice. Arch Biochem Biophys 380: 274–284 ( 2000)
Furukawa S, Murakami K, Nishikawa M, Nakayama O, Hino M . FR258900, a novel glycogen phosphorylase inhibitor isolated from fungus No. 138354. II. Anti-hyperglycemic effects in diabetic animal models. J Antibiot 58: 503–506 ( 2005)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Furukawa, S., Tsurumi, Y., Murakami, K. et al. FR258900, a Novel Glycogen Phosphorylase Inhibitor Isolated from Fungus No. 138354. J Antibiot 58, 497–502 (2005). https://doi.org/10.1038/ja.2005.66
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ja.2005.66
Keywords
This article is cited by
-
Targeting hepatic glucose metabolism in the treatment of type 2 diabetes
Nature Reviews Drug Discovery (2016)
-
FR258900, a Novel Glycogen Phosphorylase Inhibitor Isolated from Fungus No. 138354
The Journal of Antibiotics (2005)