Assessment of the Phenolic Profiles, Hypoglycemic Activity, and Molecular Mechanism of Different Highland Barley (Hordeum vulgare L.) Varieties.

Na Deng,Bisheng Zheng,Rui Hai Liu,Tong Li

doi:10.3390/ijms21041175

Na Deng, Bisheng Zheng + Show 2 more

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https://doi.org/10.3390/ijms21041175

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Abstract

The phenolic profiles, hypoglycemic activity, and molecular mechanism of the effect on type 2 diabetes mellitus (T2DM) of four highland barley varieties were investigated in the present study. The fundamental phenolics in highland barley were ferulic acid, naringin, and catechin, which mainly existed in bound form. These varieties showed favorable hypoglycemic activity via inhibition of α-glucosidase and α-amylase activities, enhancement of glucose consumption, glycogen accumulation and glycogen synthase 2 (GYS2) activity, and down-regulation of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities. Specifically, ZQ320 variety exhibited the strongest hypoglycemic activity compared to the other varieties. Highland barley phenolics could inhibit gluconeogenesis and motivate glycogen synthesis via down-regulating the gene expression of G6Pase, PEPCK, and glycogen synthase kinase 3β (GSK3β), while activating the expression of insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3 kinase (PI3K), serine/threonine kinase (Akt), GYS2, and glucose transporter type 4 (GLUT4). Therefore, phenolics from highland barley could be served as suitable candidates for therapeutic agent in T2DM to improve human health.

Highlights

Diabetes mellitus (DM), a widespread chronic metabolic disorder with high morbidity, mortality, and healthcare expenditure, is usually characterized by persistent hyperglycemia and disorders of glucose, lipid, and protein metabolism [1,2]
DM is usually classified into four main categories: type 1 diabetes mellitus, type 2 diabetes mellitus (T2DM), gestational diabetes mellitus, and others, such as type 3 diabetes mellitus [3]
T2DM is a non-insulin-dependent diabetes caused by insulin resistance (IR) and pancreatic β-cell dysfunction in hepatic, adipose, and muscle tissues, which accounts for more than 90% of diabetic patients [4]

Summary

Introduction

Diabetes mellitus (DM), a widespread chronic metabolic disorder with high morbidity, mortality, and healthcare expenditure, is usually characterized by persistent hyperglycemia and disorders of glucose, lipid, and protein metabolism [1,2]. The main drug therapies for T2DM patients are insulin and synthetic medications, such as α-glucosidase inhibitor, biguanides, thiazolidinediones, and rosiglitazone. These drugs often have many undesirable adverse effects, including weight gain, drug resistance, and hypoglycemia [5]. More investigations on novel medicines and therapies to improve treatment efficacy, reducing healthcare expenditure, and complications of T2DM are urgently warranted. The use of natural polyphenols (e.g., ginsenoside Rk3, mangiferin, and mulberry flavonoids) with low toxicity and side effects as alternative agents for the prevention and management of T2DM has aroused much attention [6,7,8]

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