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This research aimed to investigate the antidiabetic activity, underlying mechanisms, and gut microbiota regulation of aloin. The insulin-resistant HepG2 (IR-HepG2) cell model and the type 2 diabetic (T2D) mouse model were successfully established using dexamethasone and a high-fat high-sucrose diet with low-dose streptozotocin, respectively. Aloin intervention increased glucose consumption and stimulated the activity of hexokinase and pyruvate dehydrogenase in IR-HepG2 cells. Additionally, it diminished the weight loss, reduced fasting blood glucose levels and hemoglobin A1c activity, and promoted glucose tolerance and fasting serum insulin activity in T2D mice. Histopathological analysis of the liver indicated hepatic protection by aloin. Additionally, aloin treatment inhibited the protein expression of c-Jun N-terminal kinases and activated that of IRS1/PI3K/Akt in the liver. Moreover, aloin modulated the bacterial community in the gut by raising the abundance of Bacteroidota and reducing the richness of Firmicutes, Proteobacteria, and Actinobacteriota. Thus, aloin ameliorated IR via activating IRS1/PI3K/Akt signaling pathway and regulating the gut microbiota, and it may be promising candidate as functional food for diabetic therapy.


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Anti-diabetic effect of aloin via JNK-IRS1/PI3K pathways and regulation of gut microbiota

Show Author's information Ruting Zhonga,1Lanbin Chena,1Yuanyuan LiuaShouxia XiebSumei Lib( )Bin Liua,cChao Zhaoa,c( )
College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China
Department of Pharmacology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China

1 The authors contributed equally to this study Peer review under responsibility of KeAi Communications Co., Ltd.]]>

Abstract

This research aimed to investigate the antidiabetic activity, underlying mechanisms, and gut microbiota regulation of aloin. The insulin-resistant HepG2 (IR-HepG2) cell model and the type 2 diabetic (T2D) mouse model were successfully established using dexamethasone and a high-fat high-sucrose diet with low-dose streptozotocin, respectively. Aloin intervention increased glucose consumption and stimulated the activity of hexokinase and pyruvate dehydrogenase in IR-HepG2 cells. Additionally, it diminished the weight loss, reduced fasting blood glucose levels and hemoglobin A1c activity, and promoted glucose tolerance and fasting serum insulin activity in T2D mice. Histopathological analysis of the liver indicated hepatic protection by aloin. Additionally, aloin treatment inhibited the protein expression of c-Jun N-terminal kinases and activated that of IRS1/PI3K/Akt in the liver. Moreover, aloin modulated the bacterial community in the gut by raising the abundance of Bacteroidota and reducing the richness of Firmicutes, Proteobacteria, and Actinobacteriota. Thus, aloin ameliorated IR via activating IRS1/PI3K/Akt signaling pathway and regulating the gut microbiota, and it may be promising candidate as functional food for diabetic therapy.

Keywords: Gut microbiota, Aloin, Antidiabetic, Insulin signaling pathway

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Publication history

Received: 31 December 2020
Revised: 14 February 2021
Accepted: 14 February 2021
Published: 11 September 2021
Issue date: January 2022

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© 2021 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

Acknowledgements

This work was supported by Key Project of the Natural Science Foundation of Fujian Province (2020J02032), Double First-Class Construction Plan of Fujian Agriculture and Forestry University (KSYLX013), and Shenzhen Key Medical Discipline Construction Fund (SZXK059).

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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