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[Eucuragen]PEG-BHD1028 Peptide Regulates Insulin Resistance and Fatty

작성자 : 엔큐라젠
작성일 : 2021-11-29 14:17:36
조회수 : 313

Article

 

PEG-BHD1028 Peptide Regulates Insulin Resistance and Fatty Acid β-Oxidation, and Mitochondrial Biogenesis by Binding to Two Heterogeneous Binding Sites of Adiponectin Receptors, AdipoR1 and AdiopR2

 

In Kyung Lee, Gyuyoup Kim, Do-Hwi Kim and Brian B. Kim

Abstract

 


Adiponectin plays multiple critical roles in modulating various physiological processes

by binding to its receptors. The functions of PEG-BHD1028, a potent novel peptid

agonist to AdipoRs, was evaluated using in vitro and in vivo models based on the

 

 

reported action spectrum of adiponectin. To confirm the design concept of

PEG-BHD1028, the binding sites and their affinities were analyzed using the SPR( Surface

 

 

Plasmon Resonance) assay. The results revealed that PEG-BHD1028 was bound to two

heterogeneous binding sites of AdipoR1 and AdipoR2 with a relatively high affinity. In

C2C12 cells, PEG-BHD1028 significantly activated AMPK and subsequent pathways and

 

enhanced fatty acid β-oxidation and mitochondrial biogenesis. Furthermore, it also

facilitated glucose uptake by lowering insulin resistance in insulin-resistant C2C12 cells.

PEG_BHD1028 significantly reduced the fasting plasma glucose level in db/db mice

following a single s.c. injection of 50, 100, and 200 ug/Kg and glucose tolerance at a

dose of 50 ug/Kg with significantly decreased insulin production.

The animals received 5, 25, and 50 ug/Kg of PEG-BHD1028 for 21days significantly lost their weight after 18days in a range of 5-7%.

These results imply the development of PEG_BHD1028 as a potential adiponectin replacement therapeutic agent.

 

*자세한 사항은 첨부파일 참고 부탁드립니다.*





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