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
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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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