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Research ArticleArticle

Novel Terpenoid-Type Quinones Isolated fromPycnanthus angolensis of Potential Utility in the Treatment of Type 2 Diabetes

Jian Luo, Jeanne Cheung, Eileen M. Yevich, John P. Clark, Joyce Tsai, Priscilla Lapresca, Rosa P. Ubillas, Diana M. Fort, Thomas J, Carlson, Richard F. Hector, Steven R. King, Christopher D. Mendez, S. D. Jolad and Gerald M. Reaven
Journal of Pharmacology and Experimental Therapeutics February 1999, 288 (2) 529-534;
Jian Luo
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Jeanne Cheung
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Eileen M. Yevich
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John P. Clark
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Joyce Tsai
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Priscilla Lapresca
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Rosa P. Ubillas
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Diana M. Fort
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Thomas J, Carlson
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Richard F. Hector
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Steven R. King
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Christopher D. Mendez
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S. D. Jolad
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Gerald M. Reaven
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Abstract

Using an ethnomedical-based drug discovery program, two previously unknown compounds (SP-18904 and SP-18905) from Pycnanthus angolensis were isolated that lower glucose concentrations in mouse models of type 2 diabetes. SP-18904 and SP-18905 are terpenoid-type quinones that significantly lowered plasma glucose concentration (p < .05) when given orally to either ob/ob or db/db mice, both of which are hyperglycemic and hyperinsulinemic. The antihyperglycemic actions of SP-18904 and SP-18905 were associated with significant decreases in plasma insulin concentrations (p < .05), suggesting that both compounds lowered glucose by enhancing insulin-mediated glucose uptake. This was supported by the insulin suppression test in ob/ob mice. Studies in hyperglycemic, insulin-deficient mice and in vitro experiments on 3T3-L1 adipocytes further supported this conclusion. As such, these two terpenoid-type quinones represent a new class of compounds of potential use in the treatment of type 2 diabetes.

Footnotes

  • Send reprint requests to: Gerald M. Reaven, M.D., Shaman Pharmaceuticals, Inc., 213 East Grand Avenue, South San Francisco, CA 94080-4812. E-mail: greaven{at}shaman.com

  • Abbreviations:
    SSPG
    steady-state plasma glucose
    SSPI
    steady-state plasma insulin
    ANOVA
    analysis of variance
    DMEM
    Dulbecco’s modified Eagle’s medium
    DMSO
    dimethylsulfoxide
    • Received April 21, 1998.
    • Accepted September 10, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 2
1 Feb 1999
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Research ArticleArticle

Novel Terpenoid-Type Quinones Isolated fromPycnanthus angolensis of Potential Utility in the Treatment of Type 2 Diabetes

Jian Luo, Jeanne Cheung, Eileen M. Yevich, John P. Clark, Joyce Tsai, Priscilla Lapresca, Rosa P. Ubillas, Diana M. Fort, Thomas J, Carlson, Richard F. Hector, Steven R. King, Christopher D. Mendez, S. D. Jolad and Gerald M. Reaven
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 529-534;

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Research ArticleArticle

Novel Terpenoid-Type Quinones Isolated fromPycnanthus angolensis of Potential Utility in the Treatment of Type 2 Diabetes

Jian Luo, Jeanne Cheung, Eileen M. Yevich, John P. Clark, Joyce Tsai, Priscilla Lapresca, Rosa P. Ubillas, Diana M. Fort, Thomas J, Carlson, Richard F. Hector, Steven R. King, Christopher D. Mendez, S. D. Jolad and Gerald M. Reaven
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 529-534;
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