Orally active osteoanabolic agent 6-C-β-D-glucopyranosyl-(2S, 3S)-(+)- 5,7, 3',4'- tetrahydroxydihydroflavonol binds to adiponectin receptors, with a preference for AdipoR1, induces adiponectin-associated signaling and improves metabolic health in a rodent model of diabetes
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
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| Creator |
Singh, A K
Joharapurkar, A A Khan, M P Mishra, J S Singh, Nidhi Yadav, Manisha Hossain, Zakir Khan, Kainat Kumar, Sudhir Dhanesha, N A Mishra, D P Maurya, Rakesh Sharma, Sharad Jain, M R Trivedi, A K Godbole, M M Gayen, J R Chattopadhyay, Naibedya Sanyal, Sabyasachi |
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| Date |
2015-02-25T07:46:53Z
2015-02-25T07:46:53Z 2014 |
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| Identifier |
Diabetes, 2014, 63(10),3530-44
http://hdl.handle.net/123456789/1428 |
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| Description |
Adiponectin is an adipocytokine that signals through plasma membrane-bound adiponectin receptors (AdipoR) -1 and -2. Plasma adiponectin depletion is associated with type 2 diabetes, obesity and cardiovascular diseases. Adiponectin therapy however, is yet unavailable owing to its large size, complex multimerization and functional differences of the multimers. We report discovery and characterization of 6-C-β-D-glucopyranosyl-(2S, 3S)-(+)- 5,7, 3',4'- tetrahydroxydihydroflavonol (GTDF) as an orally active adiponectin mimetic. GTDF interacted with both AdipoRs, with a preference for AdipoR1. It induced adiponectin-associated signaling and enhanced glucose uptake and fatty acid oxidation in vitro, which were augmented or abolished by AdipoR1 overexpression or silencing respectively. GTDF improved metabolic health, characterized by elevated glucose-clearance, β-cell-survival, reduced steatohepatitis, browning of white adipose tissue and improved lipid profile in an AdipoR1-expressing but not an AdipoR1-depleted strain of diabetic mice. The discovery of GTDF as an adiponectin mimetic provides a promising therapeutic tool for the treatment of metabolic diseases.
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1329373 bytes
application/pdf |
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en
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CSIR-CDRI Communication No. 8700
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Osteoanabolic
Adiponectin |
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| Title |
Orally active osteoanabolic agent 6-C-β-D-glucopyranosyl-(2S, 3S)-(+)- 5,7, 3',4'- tetrahydroxydihydroflavonol binds to adiponectin receptors, with a preference for AdipoR1, induces adiponectin-associated signaling and improves metabolic health in a rodent model of diabetes
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Article
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