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Glucose lowering effect of montbretin A in Zucker Diabetic Fatty rats

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Abstract

Diabetes is an increasingly prevalent disease state with a global impact. It is important that effective and cost-efficient methods be developed to treat this disease state. Zucker diabetic fatty rats, an animal model of type 2 diabetes, were treated with montbretin A (MbA), a selective human pancreatic α-amylase inhibitor, isolated from the corms of the Crocosmia crocosmiiflora plant that may have potential as a glucose-lowering agent. The study purpose was to determine if MbA was an orally effective treatment for diabetes. The effect of MbA was compared to a current clinical treatment modality, acarbose that is associated with gastrointestinal side effects known to affect patient compliance. MbA and acarbose were administered daily in the drinking water. Body weight and fluid intake were measured daily to calculate dose consumption. Plasma glucose levels were determined twice weekly in both the fed and fasted state. At termination samples were collected to assess increased risk of secondary complications related to diabetes and oxidative stress. There was no effect of either MbA or acarbose treatment on insulin levels. Plasma glucose levels were significantly lower following MbA treatment in the ZT group which persisted throughout the study period (day 49: 12.1 ± 1.2 mM). However, while there was an initial decrease in plasma glucose levels in the acarbose-treated fatty group, this effect was not sustained (day 49: 20.6 ± 1.3 mM) through to termination. MbA improved the oxidative status of the fatty diabetic animals as well as attenuated markers for increased risk of cardiovascular complications associated with diabetes. This study demonstrated that, at a lower dose as compared to acarbose (10 mg/kg/day), chronic oral administration of MbA (7.5 mg/kg/day) was an effective glucose-lowering agent in the treatment of type 2 diabetes.

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Acknowledgments

We thank Chris Hii, Pamela Lincez, and Kelly Liu for technical assistance. This work was supported by Operating and Proof of Principle Grants from the Canadian Institutes of Health Research [CIHR-Reference Numbers (FRN): 111082, 200704PPP (to GDB and SGW)], an Operating Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) to RJA, and through the CDRD-Pfizer Innovation Fund. SGW is supported by a Tier 1 Canada Research Chair.

Author contributions

JC supervised the extraction and purification of montbretin A. All were involved in the conceptual design of experiments. VGY, SM, and JHM performed the animal studies. Writing was primarily done by VGY and JOHM with contributions from all.

Funding

The University of British Columbia holds a patent on the use of montbretin A as a blood glucose-controlling agent with RJA, GDB, and SGW as inventors.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada

    Violet G. Yuen, Sally Mustafa & John H. McNeill

  2. Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

    Steven G. Withers & Gary D. Brayer

  3. Department of Chemistry, Faculty of Science, University of British Columbia, Vancouver, BC, Canada

    Steven G. Withers & Raymond J. Andersen

  4. Department of Earth, Ocean and Atmospheric Sciences, University of British Columbia, Vancouver, BC, Canada

    Raymond J. Andersen

  5. Centre for Drug Research and Development, University of British Columbia, Vancouver, BC, Canada

    John Coleman

Authors
  1. Violet G. Yuen
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  2. John Coleman
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  3. Steven G. Withers
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  4. Raymond J. Andersen
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  5. Gary D. Brayer
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  6. Sally Mustafa
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  7. John H. McNeill
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Correspondence to John H. McNeill.

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Yuen, V.G., Coleman, J., Withers, S.G. et al. Glucose lowering effect of montbretin A in Zucker Diabetic Fatty rats. Mol Cell Biochem 411, 373–381 (2016). https://doi.org/10.1007/s11010-015-2599-4

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  • DOI: https://doi.org/10.1007/s11010-015-2599-4

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