Orally active osteoanabolic agent GTDF binds to adiponectin receptors, with a preference for adipoR1, induces adiponectin-associated signaling, and improves metabolic health in a rodent model of diabetes

Abhishek Kumar Singh, Amit Arvind Joharapurkar, Mohd Parvez Khan, Jay Sharan Mishra, Nidhi Singh, Manisha Yadav, Zakir Hossain, Kainat Khan, Sudhir Kumar, Nirav Anilkumar Dhanesha, Devendra Pratap Mishra, Rakesh Maurya, Sharad Sharma, Mukul Rameshchandra Jain, Arun Kumar Trivedi, Madan Madhav Godbole, Jiaur Rahaman Gayen, Naibedya Chattopadhyay, Sabyasachi Sanyal

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Adiponectin is an adipocytokine that signals through plasma membrane-bound adiponectin receptors 1 and 2 (AdipoR1 and -2). Plasma adiponectin depletion is associated with type 2 diabetes, obesity, and cardio-vascular diseases. Adiponectin therapy, however, is yet unavailable owing to its large size, complex multi merization, 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 AdipoRI overexpression or silencing, respectively. GTDF improved metabolic health, characterized by elevated glucose clearance, ß-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.

Original languageEnglish (US)
Pages (from-to)3530-3540
Number of pages11
JournalDiabetes
Volume63
Issue number10
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

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Adiponectin Receptors
Adiponectin
Rodentia
Health
Glucose
White Adipose Tissue
Adipokines
Metabolic Diseases
Fatty Liver
Vascular Diseases
Type 2 Diabetes Mellitus
Cell Survival
Fatty Acids
Obesity
Cell Membrane
Lipids
Therapeutics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Orally active osteoanabolic agent GTDF binds to adiponectin receptors, with a preference for adipoR1, induces adiponectin-associated signaling, and improves metabolic health in a rodent model of diabetes. / Singh, Abhishek Kumar; Joharapurkar, Amit Arvind; Khan, Mohd Parvez; Mishra, Jay Sharan; Singh, Nidhi; Yadav, Manisha; Hossain, Zakir; Khan, Kainat; Kumar, Sudhir; Dhanesha, Nirav Anilkumar; Mishra, Devendra Pratap; Maurya, Rakesh; Sharma, Sharad; Jain, Mukul Rameshchandra; Trivedi, Arun Kumar; Godbole, Madan Madhav; Gayen, Jiaur Rahaman; Chattopadhyay, Naibedya; Sanyal, Sabyasachi.

In: Diabetes, Vol. 63, No. 10, 01.10.2014, p. 3530-3540.

Research output: Contribution to journalArticle

Singh, AK, Joharapurkar, AA, Khan, MP, Mishra, JS, Singh, N, Yadav, M, Hossain, Z, Khan, K, Kumar, S, Dhanesha, NA, Mishra, DP, Maurya, R, Sharma, S, Jain, MR, Trivedi, AK, Godbole, MM, Gayen, JR, Chattopadhyay, N & Sanyal, S 2014, 'Orally active osteoanabolic agent GTDF binds to adiponectin receptors, with a preference for adipoR1, induces adiponectin-associated signaling, and improves metabolic health in a rodent model of diabetes', Diabetes, vol. 63, no. 10, pp. 3530-3540. https://doi.org/10.2337/db13-1619
Singh, Abhishek Kumar ; Joharapurkar, Amit Arvind ; Khan, Mohd Parvez ; Mishra, Jay Sharan ; Singh, Nidhi ; Yadav, Manisha ; Hossain, Zakir ; Khan, Kainat ; Kumar, Sudhir ; Dhanesha, Nirav Anilkumar ; Mishra, Devendra Pratap ; Maurya, Rakesh ; Sharma, Sharad ; Jain, Mukul Rameshchandra ; Trivedi, Arun Kumar ; Godbole, Madan Madhav ; Gayen, Jiaur Rahaman ; Chattopadhyay, Naibedya ; Sanyal, Sabyasachi. / Orally active osteoanabolic agent GTDF binds to adiponectin receptors, with a preference for adipoR1, induces adiponectin-associated signaling, and improves metabolic health in a rodent model of diabetes. In: Diabetes. 2014 ; Vol. 63, No. 10. pp. 3530-3540.
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AU - Khan, Mohd Parvez

AU - Mishra, Jay Sharan

AU - Singh, Nidhi

AU - Yadav, Manisha

AU - Hossain, Zakir

AU - Khan, Kainat

AU - Kumar, Sudhir

AU - Dhanesha, Nirav Anilkumar

AU - Mishra, Devendra Pratap

AU - Maurya, Rakesh

AU - Sharma, Sharad

AU - Jain, Mukul Rameshchandra

AU - Trivedi, Arun Kumar

AU - Godbole, Madan Madhav

AU - Gayen, Jiaur Rahaman

AU - Chattopadhyay, Naibedya

AU - Sanyal, Sabyasachi

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