Hypoxylonol F Isolated from <i>Annulohypoxylon annulatum</i> Improves Insulin Secretion by Regulating Pancreatic β-cell Metabolism

Insulin plays a key role in glucose homeostasis and is hence used to treat hyperglycemia, the main characteristic of diabetes mellitus. <i>Annulohypoxylon annulatum</i> is an inedible ball-shaped wood-rotting fungus, and hypoxylon F is one of the major compounds of <i>A. annulatum&...

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Main Authors: Dahae Lee, Buyng Su Hwang, Pilju Choi, Taejung Kim, Youngseok Kim, Bong Geun Song, Noriko Yamabe, Gwi Seo Hwang, Ki Sung Kang, Jungyeob Ham
Format: Article
Language:English
Published: MDPI AG 2019-08-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/9/8/335
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author Dahae Lee
Buyng Su Hwang
Pilju Choi
Taejung Kim
Youngseok Kim
Bong Geun Song
Noriko Yamabe
Gwi Seo Hwang
Ki Sung Kang
Jungyeob Ham
author_facet Dahae Lee
Buyng Su Hwang
Pilju Choi
Taejung Kim
Youngseok Kim
Bong Geun Song
Noriko Yamabe
Gwi Seo Hwang
Ki Sung Kang
Jungyeob Ham
author_sort Dahae Lee
collection DOAJ
description Insulin plays a key role in glucose homeostasis and is hence used to treat hyperglycemia, the main characteristic of diabetes mellitus. <i>Annulohypoxylon annulatum</i> is an inedible ball-shaped wood-rotting fungus, and hypoxylon F is one of the major compounds of <i>A. annulatum</i>. The aim of this study is to evaluate the effects of hypoxylonol F isolated from <i>A. annulatum</i> on insulin secretion in INS-1 pancreatic &#946;-cells and demonstrate the molecular mechanisms involved. Glucose-stimulated insulin secretion (GSIS) values were evaluated using a rat insulin ELISA kit. Moreover, the expression of proteins related to pancreatic &#946;-cell metabolism and insulin secretion was evaluated using Western blotting. Hypoxylonol F isolated from <i>A. annulatum</i> was found to significantly enhance glucose-stimulated insulin secretion without inducing cytotoxicity. Additionally, hypoxylonol F enhanced insulin receptor substrate-2 (IRS-2) levels and activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. Interestingly, it also modulated the expression of peroxisome proliferator-activated receptor &#947; (PPAR&#947;) and pancreatic and duodenal homeobox 1 (PDX-1). Our findings showed that <i>A. annulatum</i> and its bioactive compounds are capable of improving insulin secretion by pancreatic &#946;-cells. This suggests that <i>A. annulatum</i> can be used as a therapeutic agent to treat diabetes.
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spelling doaj.art-26d16dc710d443f99d33e13c88cc7e2f2022-12-21T22:46:25ZengMDPI AGBiomolecules2218-273X2019-08-019833510.3390/biom9080335biom9080335Hypoxylonol F Isolated from <i>Annulohypoxylon annulatum</i> Improves Insulin Secretion by Regulating Pancreatic β-cell MetabolismDahae Lee0Buyng Su Hwang1Pilju Choi2Taejung Kim3Youngseok Kim4Bong Geun Song5Noriko Yamabe6Gwi Seo Hwang7Ki Sung Kang8Jungyeob Ham9School of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaFreshwater Bioresources Utilization Bureau, Nakdonggang National Institute of Biological Resources, Sangju 37242, KoreaNatural Products Research Institute, Korea Institute of Science and Technology, Gangneung 25451, KoreaNatural Products Research Institute, Korea Institute of Science and Technology, Gangneung 25451, KoreaNatural Products Research Institute, Korea Institute of Science and Technology, Gangneung 25451, KoreaNatural Products Research Institute, Korea Institute of Science and Technology, Gangneung 25451, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaFreshwater Bioresources Utilization Bureau, Nakdonggang National Institute of Biological Resources, Sangju 37242, KoreaInsulin plays a key role in glucose homeostasis and is hence used to treat hyperglycemia, the main characteristic of diabetes mellitus. <i>Annulohypoxylon annulatum</i> is an inedible ball-shaped wood-rotting fungus, and hypoxylon F is one of the major compounds of <i>A. annulatum</i>. The aim of this study is to evaluate the effects of hypoxylonol F isolated from <i>A. annulatum</i> on insulin secretion in INS-1 pancreatic &#946;-cells and demonstrate the molecular mechanisms involved. Glucose-stimulated insulin secretion (GSIS) values were evaluated using a rat insulin ELISA kit. Moreover, the expression of proteins related to pancreatic &#946;-cell metabolism and insulin secretion was evaluated using Western blotting. Hypoxylonol F isolated from <i>A. annulatum</i> was found to significantly enhance glucose-stimulated insulin secretion without inducing cytotoxicity. Additionally, hypoxylonol F enhanced insulin receptor substrate-2 (IRS-2) levels and activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. Interestingly, it also modulated the expression of peroxisome proliferator-activated receptor &#947; (PPAR&#947;) and pancreatic and duodenal homeobox 1 (PDX-1). Our findings showed that <i>A. annulatum</i> and its bioactive compounds are capable of improving insulin secretion by pancreatic &#946;-cells. This suggests that <i>A. annulatum</i> can be used as a therapeutic agent to treat diabetes.https://www.mdpi.com/2218-273X/9/8/335<i>Annulohypoxylon annulatum</i>insulinPI3KAktPPARγPDX-1
spellingShingle Dahae Lee
Buyng Su Hwang
Pilju Choi
Taejung Kim
Youngseok Kim
Bong Geun Song
Noriko Yamabe
Gwi Seo Hwang
Ki Sung Kang
Jungyeob Ham
Hypoxylonol F Isolated from <i>Annulohypoxylon annulatum</i> Improves Insulin Secretion by Regulating Pancreatic β-cell Metabolism
Biomolecules
<i>Annulohypoxylon annulatum</i>
insulin
PI3K
Akt
PPARγ
PDX-1
title Hypoxylonol F Isolated from <i>Annulohypoxylon annulatum</i> Improves Insulin Secretion by Regulating Pancreatic β-cell Metabolism
title_full Hypoxylonol F Isolated from <i>Annulohypoxylon annulatum</i> Improves Insulin Secretion by Regulating Pancreatic β-cell Metabolism
title_fullStr Hypoxylonol F Isolated from <i>Annulohypoxylon annulatum</i> Improves Insulin Secretion by Regulating Pancreatic β-cell Metabolism
title_full_unstemmed Hypoxylonol F Isolated from <i>Annulohypoxylon annulatum</i> Improves Insulin Secretion by Regulating Pancreatic β-cell Metabolism
title_short Hypoxylonol F Isolated from <i>Annulohypoxylon annulatum</i> Improves Insulin Secretion by Regulating Pancreatic β-cell Metabolism
title_sort hypoxylonol f isolated from i annulohypoxylon annulatum i improves insulin secretion by regulating pancreatic β cell metabolism
topic <i>Annulohypoxylon annulatum</i>
insulin
PI3K
Akt
PPARγ
PDX-1
url https://www.mdpi.com/2218-273X/9/8/335
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