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The estrogen receptor {alpha}-selective agonist propyl pyrazole triol improves glucose tolerance in ob/ob mice; potential molecular mechanisms
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2008 (English)In: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 1479-6805, Vol. 199, no 2, 275-286 p.Article in journal (Refereed) PublishedText
Abstract [en]

The aim of this study was to validate the role of estrogen receptor alpha (ERalpha) signaling in the regulation of glucose metabolism, and to compare the molecular events upon treatment with the ERalpha-selective agonist propyl pyrazole triol (PPT) or 17beta-estradiol (E(2)) in ob/ob mice. Female ob/ob mice were treated with PPT, E(2) or vehicle for 7 or 30 days. Intraperitoneal glucose and insulin tolerance tests were performed, and insulin secretion was determined from isolated islets. Glucose uptake was assayed in isolated skeletal muscle and adipocytes. Gene expression profiling in the liver was performed using Affymetrix microarrays, and the expression of selected genes was studied by real-time PCR analysis. PPT and E(2) treatment improved glucose tolerance and insulin sensitivity. Fasting blood glucose levels decreased after 30 days of PPT and E(2) treatment. However, PPT and E(2) had no effect on insulin secretion from isolated islets. Basal and insulin-stimulated glucose uptake in skeletal muscle and adipose tissue were similar in PPT and vehicle-treated ob/ob mice. Hepatic lipid content was decreased after E(2) treatment. In the liver, treatment with E(2) and PPT increased and decreased the respective expression levels of the transcription factor signal transducer and activator of transcription 3, and of glucose-6-phosphatase. In summary, our data demonstrate that PPT exerts anti-diabetic effects, and these effects are mediated via ERalpha.

Place, publisher, year, edition, pages
2008. Vol. 199, no 2, 275-286 p.
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Cell Biology
URN: urn:nbn:se:sh:diva-29031DOI: 10.1677/JOE-08-0192ISI: 000260768600013PubMedID: 18757549OAI: diva2:891671

Lundholm, L Bryzgalova, G Gao, H Portwood, N Falt, S Berndt, K D Dicker, A Galuska, D Zierath, J R Gustafsson, J-A Efendic, S Dahlman-Wright, K Khan, A Research Support, Non-U.S. Gov't England The Journal of endocrinology J Endocrinol. 2008 Nov;199(2):275-86. Epub 2008 Aug 29.

Available from: 2016-01-07 Created: 2016-01-07 Last updated: 2016-01-08Bibliographically approved

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