Myricetin Increases Circulating Adropin Level after Activation of Glucagon-like Peptide 1 (GLP-1) Receptor in Type-1 Diabetic Rats

Myricetin is a common plant-derived flavonoid, considered an agonist of glucagon-like peptide 1 (GLP-1) receptor. It improves glycemic control and helps reduce body weight in diabetic subjects. The potential mechanisms of action of myricetin in this context might be enhancing the secretion of β-endo...

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Main Authors: Ying-Xiao Li, Kai-Chun Cheng, I-Min Liu, Ho-Shan Niu
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/15/2/173
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author Ying-Xiao Li
Kai-Chun Cheng
I-Min Liu
Ho-Shan Niu
author_facet Ying-Xiao Li
Kai-Chun Cheng
I-Min Liu
Ho-Shan Niu
author_sort Ying-Xiao Li
collection DOAJ
description Myricetin is a common plant-derived flavonoid, considered an agonist of glucagon-like peptide 1 (GLP-1) receptor. It improves glycemic control and helps reduce body weight in diabetic subjects. The potential mechanisms of action of myricetin in this context might be enhancing the secretion of β-endorphin (BER) to activate peripheral μ-opioid receptors. Moreover, adropin is a nutritionally regulated peptide hormone, which regulates energy metabolism, and plays a role in ameliorating diabetes. Because their mechanisms of insulin sensitivity are closely related, we hypothesized that myricetin may interact with adropin and plasma BER. The present study investigated the glucose-lowering effect of acute and chronic treatments of myricetin in type-1 diabetic rats. Plasma BER and adropin levels were determined by enzyme-linked immunosorbent assay (ELISA). The secretion of BER was measured in rats who received adrenalectomy. The changes in adropin gene (<i>Enho</i>) or mRNA level of GLP-1 receptor were measured using qPCR analysis. The results showed that myricetin dose-dependently increased plasma BER and adropin levels like the reduction of hyperglycemia after bolus injection as acute treatment. In addition, these effects of myricetin were inhibited by the antagonist of GLP-1 receptor. Moreover, in HepG2 cell line, myricetin induced GLP-1 receptor activation, which modulated the expression of adropin. In diabetic rats, the plasma adropin increased by myricetin is mainly through endogenous β-endorphin after activation of GLP-1 receptor via bolus injection as acute treatment. Additionally, chronic treatment with myricetin increased adropin secretion in diabetic rats. In conclusion, our results provide a new finding that activation of opioid μ-receptor in the liver may enhance circulating adropin in animals.
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spelling doaj.art-62098a02f42e47519c6a3e1c8187adc12023-11-23T21:34:09ZengMDPI AGPharmaceuticals1424-82472022-01-0115217310.3390/ph15020173Myricetin Increases Circulating Adropin Level after Activation of Glucagon-like Peptide 1 (GLP-1) Receptor in Type-1 Diabetic RatsYing-Xiao Li0Kai-Chun Cheng1I-Min Liu2Ho-Shan Niu3Department of Nursing, Tzu Chi University of Science and Technology, Hualien 970302, TaiwanDepartment of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung County 90741, TaiwanDepartment of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung County 90741, TaiwanDepartment of Nursing, Tzu Chi University of Science and Technology, Hualien 970302, TaiwanMyricetin is a common plant-derived flavonoid, considered an agonist of glucagon-like peptide 1 (GLP-1) receptor. It improves glycemic control and helps reduce body weight in diabetic subjects. The potential mechanisms of action of myricetin in this context might be enhancing the secretion of β-endorphin (BER) to activate peripheral μ-opioid receptors. Moreover, adropin is a nutritionally regulated peptide hormone, which regulates energy metabolism, and plays a role in ameliorating diabetes. Because their mechanisms of insulin sensitivity are closely related, we hypothesized that myricetin may interact with adropin and plasma BER. The present study investigated the glucose-lowering effect of acute and chronic treatments of myricetin in type-1 diabetic rats. Plasma BER and adropin levels were determined by enzyme-linked immunosorbent assay (ELISA). The secretion of BER was measured in rats who received adrenalectomy. The changes in adropin gene (<i>Enho</i>) or mRNA level of GLP-1 receptor were measured using qPCR analysis. The results showed that myricetin dose-dependently increased plasma BER and adropin levels like the reduction of hyperglycemia after bolus injection as acute treatment. In addition, these effects of myricetin were inhibited by the antagonist of GLP-1 receptor. Moreover, in HepG2 cell line, myricetin induced GLP-1 receptor activation, which modulated the expression of adropin. In diabetic rats, the plasma adropin increased by myricetin is mainly through endogenous β-endorphin after activation of GLP-1 receptor via bolus injection as acute treatment. Additionally, chronic treatment with myricetin increased adropin secretion in diabetic rats. In conclusion, our results provide a new finding that activation of opioid μ-receptor in the liver may enhance circulating adropin in animals.https://www.mdpi.com/1424-8247/15/2/173myricetinadropinopioid μ-receptorβ-endorphinGLP-1diabetes
spellingShingle Ying-Xiao Li
Kai-Chun Cheng
I-Min Liu
Ho-Shan Niu
Myricetin Increases Circulating Adropin Level after Activation of Glucagon-like Peptide 1 (GLP-1) Receptor in Type-1 Diabetic Rats
Pharmaceuticals
myricetin
adropin
opioid μ-receptor
β-endorphin
GLP-1
diabetes
title Myricetin Increases Circulating Adropin Level after Activation of Glucagon-like Peptide 1 (GLP-1) Receptor in Type-1 Diabetic Rats
title_full Myricetin Increases Circulating Adropin Level after Activation of Glucagon-like Peptide 1 (GLP-1) Receptor in Type-1 Diabetic Rats
title_fullStr Myricetin Increases Circulating Adropin Level after Activation of Glucagon-like Peptide 1 (GLP-1) Receptor in Type-1 Diabetic Rats
title_full_unstemmed Myricetin Increases Circulating Adropin Level after Activation of Glucagon-like Peptide 1 (GLP-1) Receptor in Type-1 Diabetic Rats
title_short Myricetin Increases Circulating Adropin Level after Activation of Glucagon-like Peptide 1 (GLP-1) Receptor in Type-1 Diabetic Rats
title_sort myricetin increases circulating adropin level after activation of glucagon like peptide 1 glp 1 receptor in type 1 diabetic rats
topic myricetin
adropin
opioid μ-receptor
β-endorphin
GLP-1
diabetes
url https://www.mdpi.com/1424-8247/15/2/173
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AT kaichuncheng myricetinincreasescirculatingadropinlevelafteractivationofglucagonlikepeptide1glp1receptorintype1diabeticrats
AT iminliu myricetinincreasescirculatingadropinlevelafteractivationofglucagonlikepeptide1glp1receptorintype1diabeticrats
AT hoshanniu myricetinincreasescirculatingadropinlevelafteractivationofglucagonlikepeptide1glp1receptorintype1diabeticrats