Document Detail

The CB-1 Receptor Antagonist Rimonabant Modulates the Interaction Between Adipocytes and Pancreatic Beta-Cells in Vitro.
MedLine Citation:
PMID:  20658443     Owner:  NLM     Status:  In-Data-Review    
BACKGROUND: Adipocytes produce signalling molecules which can act on target cells including pancreatic beta-cells. In previous studies we found adipocytes to directly stimulate insulin secretion and the proliferation of pancreatic beta-cells in vitro. Rimonabant acts as an antagonist at the cannabinoid-1 (CB-1) receptor which is expressed on adipocytes. Rimonabant decreases insulin levels in vivo. This effect can either be explained by improving insulin sensitivity or by effects on beta-cells including the modulation of adipocyte - beta-cell interactions.
OBJECTIVES: To test how pre-treatment of primary human adipocytes with rimonabant affects the cross-talk between adipocytes and pancreatic beta-cells in vitro.
RESULTS: Rimonabant had no direct effect on insulin secretion or beta-cell proliferation at a concentration range from 1 nM to 1 μM. This is in line with previous findings showing that in the murine pancreas CB-1 receptors are preferentially expressed on non-beta-cells, while rimonabant is a selective blocker of CB-1 receptors. We found fat-cell conditioned-medium without (FCCM) and after pre-treatment for 24 h with 100 nM rimonabant (FCCM-RB) to induce insulin secretion from primary murine beta-cells to a similar extent. Proliferation of a pancreatic beta-cell line was enhanced by FCCM to 219%, while FCCM-RB inhibited proliferation to 53%. As we previously found Wnt-signalling to mediate effects of adipocytes on beta-cell proliferation we tested the ability of FCCM and FCCM-RB to activate canonical Wnt-signalling in target cells. However, there was no significant difference between the groups: FCCM and FCCM-RB stimulated Wnt reporter gene activity to 181% and 179%, respectively. In addition, there was no significant difference in adiponectin levels between FCCM and FCCM-RB (56.8 vs. 58.1 ng/ml), showing that adiponectin does not mediate the differential effects on beta-cell proliferation by FCCM and FCCM-RB.
CONCLUSION: Our data show that rimonabant modulates the adipocyte - beta-cell interaction with respect to beta-cell proliferation and indicate that signalling molecules other than adiponectin and components of the Wnt pathway mediate this cross-talk.
F Ulgen; M C Kühn; K Cupisti; C Herder; H S Willenberg; M Schott; W A Scherbaum; S Schinner
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Publication Detail:
Type:  Journal Article     Date:  2010-07-23
Journal Detail:
Title:  Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association     Volume:  119     ISSN:  1439-3646     ISO Abbreviation:  Exp. Clin. Endocrinol. Diabetes     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9505926     Medline TA:  Exp Clin Endocrinol Diabetes     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  41-6     Citation Subset:  IM    
Copyright Information:
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.
Department of Endocrinology, Diabetes and Rheumatology, University Hospital Düsseldorf, Düsseldorf, Germany.
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