Association of PI3K/AKT/mTOR pathway genetic variants with type 2 diabetes mellitus in Chinese

Yin, Xiaoxing; Xu, Zhiye; Zhang, Ziyi; Li, Lin; Pan, Qianqian; Zheng, Fenping; Li, Hong

doi:10.1016/j.diabres.2017.04.002

Cited by 52 publications

(31 citation statements)

References 21 publications

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“…Moreover, the expression levels of IRS1, IRS2, PI3K, and GSK‐3β were significantly decreased in the liver and muscle tissues in the T2DM group compared with the control group. Many studies have suggested that insulin activates the downstream section of the PI3K/Akt signaling pathway by phosphorylating IRS1/IRS2 to regulate the glucose metabolism process . Our results suggested that the PI3K/Akt signaling pathway mediated the development of T2DM.…”

Section: Discussionsupporting

confidence: 54%

Comparative medical characteristics of ZDF‐T2DM rats during the course of development to late stage disease

Pang

Liu

et al. 2018

Anim Models and Exp Med

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Background There are few reports on the comparative medical characteristics of type 2 diabetes models in late stage. An analysis of comparative medical characteristics of Zucker diabetic fatty type 2 diabetes mellitus ( ZDF ‐T2 DM ) rats during the course of development to late stage disease was performed. Methods In this study, ZDF rats were fed with high‐sugar and high‐fat diets to raise the fasting blood glucose, and develop of type 2 diabetes. At the late stage of T2 DM , the preliminary comparative medical characteristics of the T2 DM model were analyzed through the detection of clinical indicators, histopathology, related cytokine levels, and insulin‐related signaling molecule expression levels. Results In the T2 DM group, the fasting blood glucose was higher than 6.8 mmol/L, the serum insulin, leptin, and adiponectin levels were significantly decreased, and glucose intolerance and insulin resistance were measured as clinical indicators. Regarding pathological indicators, a large number of pancreatic islet cells showed the reduction of insulin secretion, resulting in damaged glycogen synthesis and liver steatosis. At the molecular level, the insulin signal transduction pathway was inhibited by decreasing the insulin receptor substrate 1 ( IRS 1), insulin receptor substrate 2 ( IRS 2), phosphatidylinositol 3 kinase ( PI 3K), and glycogen synthesis kinase 3β ( GSK ‐3β) expression levels. Conclusion The results show that the ZDF /T2 DM rats have typical clinical, histopathological, and molecular characteristics of human T2 DM and thus can be used as an effective model for T2 DM drug development and treatment of advanced T2 DM .

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Section: Discussionsupporting

confidence: 54%

Comparative medical characteristics of ZDF‐T2DM rats during the course of development to late stage disease

Pang

Liu

et al. 2018

Anim Models and Exp Med

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“…Akt can directly make Foxo1 phosphorylate, Phosphorylated FOX1 can be transferred from the nucleus to the cytoplasm and then lose activity (Barthel et al, 2005 ). Epidemiological statistics show that the polymorphism of Akt gene is closely related to diabetes mellitus, it can be activated by phosphorylation then play a role of anti-β cell apoptosis and promote the survival of β cells (Blaabjerg et al, 2014 ; Yin et al, 2017 ). Our observations suggest that high fat intake in KKAy mice can promote Foxo1 protein expression.…”

Section: Discussionmentioning

confidence: 99%

Jiang Tang Xiao Ke Granule Play an Anti-diabetic Role in Diabetic Mice Pancreatic Tissue by Regulating the mRNAs and MicroRNAs Associated with PI3K-Akt Signaling Pathway

Zhang

et al. 2017

Front. Pharmacol.

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Purpose: To investigate the effect of JTXK granule on the expression pattern of miRNA in pancreatic tissue of KKAy diabetic mice, and to explore the molecular mechanism and pathways of JTXK granule in anti-diabetic effect.Methods: We used high fat diet (HFD) to induce the KKAy diabetic mice and screened the differentially expressed miRNAs (DEMs) between JTXK-treated group (n = 6) and the diabetic group (n = 6) using MicroRNA (miRNA) Microarray. C57BL/6J mice were given a normal diet as the control group (n = 6). Subsequently, miRNA target gene prediction, GO and Pathway analysis were used to explore the function of DEMs. Finally, the mechanism of anti-diabetic effects of JTXK granule was tested by in vitro INS-1 pancreatic β-cell experiment.Results: The blood glucose and body weight of JTXK-treated group was significantly lower compared with the model group. Moreover, a total of 45 miRNAs with significant differences were detected in the model group and the JTXK-treated group (P ≤ 0.05, Fold Change > 2). Further, miRNA-mRNA analysis showed that the differential expression of mmu-miR-192-5p, mmu-miR-291a-3p, mmu-miR-320-3p, mmu-miR-139-5p and mmu-miR-378a-3p are closely related to pancreatic histological changes. In addition, pathway analysis showed that the DEMs were closely related to PI3K-Akt Signaling Pathway. Furthermore, the levels of serine/threonine-protein kinase (Akt), phosphorylated Akt (p-Akt) and phosphorylated forkhead transcription factor O1 (p-Foxo1) in INS-1-FOXO1 overexpressing model cells were lower than those in normal group, while JTXK granules could increase the expression of Akt, p-Akt and p-Foxo1.Conclusions: The results showed that JTXK granule could play an anti-diabetic role by regulating the mRNA and miRNAs associated with PI3K-Akt pathway in diabetic mice pancreatic tissue.

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“…miRNAs can also regulate the expression of genes associated with dental germ formation quantity ( 6 ). Researchers have previously knocked out Dicer enzyme, which is essential for the formation of mature miRNAs, and observed an increase in the number of dental germs in mice, as well as partial edentia ( 13 ). miRNAs also serve important regulatory roles in dental pulp regeneration research ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

“…Researchers have previously knocked out Dicer enzyme, which is essential for the formation of mature miRNAs, and observed an increase in the number of dental germs in mice, as well as partial edentia ( 13 ). miRNAs also serve important regulatory roles in dental pulp regeneration research ( 13 ). Results of the present study demonstrated that overexpression of miR-139-5p promoted cell growth and induced skeletal myogenic differentiation of ADSCs.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑139‑5p elevates skeletal myogenic differentiation of human adult dental pulp stem cells through Wnt/β‑catenin signaling pathway

Xie

Shen

2018

Exp Ther Med

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The aim of the present study was to identify a microRNA (miRNA or miR)-based biomarker and therapeutic target for skeletal myogenic differentiation of human adult dental pulp stem cells (ADSCs). miRNA expression was measured using reverse transcription-quantitative polymerase chain reaction; cell viability assay and lactate dehydrogenase (LDH) activity levels were measured using MTT and LDH activity kits, respectively. Apoptosis assay and caspase-3/9 activity levels were measured using flow cytometry and caspase-3/9 activity kits, respectively. Western blot analysis and immunofluorescence microscopy measured the protein expression of myocyte-specific enhancer factor 2C, myogenic differentiation 1, myosin heavy chain, Wnt and β-catenin. Overexpression of miR-139-5p promoted cell growth and induced skeletal myogenic differentiation of ADSCs. Downregulation of miR-139-5p inhibited cell growth and reduced skeletal myogenic differentiation of ADSCs. Overexpression of miR-139-5p induced Wnt/β-catenin signaling pathway and Wnt/β-catenin signaling pathway was suppressed by anti-miR-139-5p in ADSCs. Wnt inhibitor reduced the effect of miR-139-5p on skeletal myogenic differentiation of ADSCs. In conclusion, miR-139-5p elevates skeletal myogenic differentiation of human ADSCs through the Wnt/β-catenin signaling pathway.

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Association of PI3K/AKT/mTOR pathway genetic variants with type 2 diabetes mellitus in Chinese

Cited by 52 publications

References 21 publications

Comparative medical characteristics of ZDF‐T2DM rats during the course of development to late stage disease

Comparative medical characteristics of ZDF‐T2DM rats during the course of development to late stage disease

Jiang Tang Xiao Ke Granule Play an Anti-diabetic Role in Diabetic Mice Pancreatic Tissue by Regulating the mRNAs and MicroRNAs Associated with PI3K-Akt Signaling Pathway

MicroRNA‑139‑5p elevates skeletal myogenic differentiation of human adult dental pulp stem cells through Wnt/β‑catenin signaling pathway

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