PMID- 33104141 OWN - NLM STAT- MEDLINE DCOM- 20210517 LR - 20210517 IS - 2042-650X (Electronic) IS - 2042-6496 (Linking) VI - 11 IP - 11 DP - 2020 Nov 18 TI - IRS-1/PI3K/Akt pathway and miRNAs are involved in whole grain highland barley (Hordeum vulgare L.) ameliorating hyperglycemia of db/db mice. PG - 9535-9546 LID - 10.1039/d0fo01990a [doi] AB - The effects of whole grain highland barley (WGH) with rich phenolics on glucose metabolism, the insulin pathway, and microRNA (miRNA) expression in db/db mice were explored in the present study. Supplementation with WGH decreased the levels of blood glucose, glycosylated serum protein (GSP), insulin, and inflammatory cytokines in db/db mice. Furthermore, WGH administration triggered a remarkable amelioration of glucose intolerance and insulin resistance. The hepatic glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxylase (PEPCK) activities and the G6PC, PEPCK, and forkhead transcription factor 1 (FOXO1) mRNA levels in the WGH-treated group were also reduced. Moreover, WGH promoted the glycogen storage in the liver via up-regulating the activities of hexokinase (HK) and glycogen synthase (GS) and the phosphorylation of glycogen synthase kinase 3beta (GSK3beta) protein, while down-regulating the GSK3beta mRNA level. The protein expression of phosphatidylinositol 3-kinase (PI3K), the phosphorylation of protein kinase B (Akt), and the mRNA levels of insulin receptor substrate-1 (IRS-1), PI3K and Akt were also up-regulated by WGH treatment. Moreover, WGH significantly augmented the expression of miRNA-26a and miRNA-451, but reduced those of miRNA-126a and miRNA-29a. These results demonstrated that WGH exhibits a hypoglycemic effect through regulating the IRS-1/PI3K/Akt pathway and related miRNAs, further modulating the expression of G6PC, PEPCK, and FOXO1 mRNAs and p-GSK3beta protein, thus inhibiting hepatic gluconeogenesis, improving glycogen synthesis and alleviating insulin resistance. Therefore, this study suggested WGH as an effective candidate to ameliorate the hyperglycemia of type 2 diabetes mellitus. FAU - Deng, Na AU - Deng N AD - Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health (111 Center), School of Food Science and Engineering, South China University of Technology, Guangzhou, 510641, China. febzheng@scut.edu.cn. FAU - Guo, Ruixue AU - Guo R FAU - Zheng, Bisheng AU - Zheng B FAU - Li, Tong AU - Li T FAU - Liu, Rui Hai AU - Liu RH LA - eng PT - Journal Article PL - England TA - Food Funct JT - Food & function JID - 101549033 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin Receptor Substrate Proteins) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Diabetes Mellitus, Type 2/*prevention & control MH - Disease Models, Animal MH - *Functional Food MH - *Hordeum MH - Hyperglycemia/*prevention & control MH - Hypoglycemic Agents/administration & dosage/pharmacology/*therapeutic use MH - Insulin Receptor Substrate Proteins/metabolism MH - Male MH - Mice MH - Mice, Obese MH - Phosphatidylinositol 3-Kinase/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Signal Transduction/drug effects EDAT- 2020/10/27 06:00 MHDA- 2021/05/18 06:00 CRDT- 2020/10/26 12:10 PHST- 2020/10/27 06:00 [pubmed] PHST- 2021/05/18 06:00 [medline] PHST- 2020/10/26 12:10 [entrez] AID - 10.1039/d0fo01990a [doi] PST - ppublish SO - Food Funct. 2020 Nov 18;11(11):9535-9546. doi: 10.1039/d0fo01990a.