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Horm Metab Res 2001; 33(12): 721-726
DOI: 10.1055/s-2001-19136
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

The Antihyperglycemic Effect of Estrone Sulfate in Genetically Obese-Diabetic (ob/ob) Mice is Associated with Reduced Hepatic Glucose-6-Phosphatase

E. B. Borthwick 1 2 , P. M. Houston 1 , M. W. H. Coughtrie 2 , A. Burchell 1
  • 1 Department of Obstetrics & Gynecology, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK
  • 2 Department of Molecular & Cellular Pathology, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK
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Publication History

Publication Date:
18 December 2001 (online)

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Excessive glucose production by the liver contributes significantly to diabetic hyperglycemia. The enzyme system glucose-6-phosphatase plays a key role in regulating hepatic glucose production and therefore its inhibition is a potential therapeutic target for the correction of hyperglycemia. It has previously been shown that sulfated steroids, such as estrone sulfate and dehydroepiandrosterone sulfate, inhibit the glucose-6-phosphatase system in vitro, principally through inhibition of endoplasmic reticulum glucose-6-phosphate transport. We report here that in the obese/diabetic ob/ob mouse model, orally administered estrone sulfate reduces the abnormally elevated hepatic glucose-6-phosphatase enzyme activity and enzyme protein levels that are characteristic in the ob/ob mouse, and that this reduction is associated with normalization of blood glucose levels. Other sulfated and non-sulfated steroids also reduced, to a lesser extent, glucose-6-phosphatase enzyme activity - with the exception of dehydroepiandrosterone sulfate, which had no apparent effect on this system in ob/ob mice. Estrone sulfate is therefore an effective antihyperglycemic agent in ob/ob mice, and the glucose-6-phosphatase system can be successfully targeted for the therapeutic management of hyperglycemia in this animal model of non-insulin-dependent diabetes mellitus.

Key words:

Diabetes - Blood Glucose - Steroid Sulfates - Hepatic Gluconeogenesis - Metabolism

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Prof. Ann Burchell

Tayside Institute of Child Health
University of Dundee
Ninewells Hospital and Medical School

DUNDEE DD1 9SY
Scotland
UK


Phone: + 44 (1382) 632-445

Fax: + 44 (1382) 632-597

Email: a.burchell@dundee.ac.uk