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

Abstract

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.

Jiang Tang Xiao Ke Granule Protects Hepatic Tissue of Diabetic Mice Through Modulation of Insulin and Ras Signaling – A Bioinformatics Analysis of MicroRNAs and mRNAs Network

“…The batch number was 20140518. Fingerprint of this granule that illustrated the main ingredients were shown in Figure 1 and in accordance with our previous study (Mo et al, 2017). Finally, the granules were stored in −4 • C refrigerator and prepared suspension of corresponding concentration with distilled water before use.…”

“…It has been found that Chinese medicine formula play a major role in the treatment of diabetes through multiple targets with various mechanisms (Zhijun et al, 2013) and so on. Our previous data have shown that JTXK Granule plays the anti-diabetic role by regulating glycolipid metabolism, resisting oxidative stress, and also protecting islet cells, which act through regulating phosphatidylinositol 3kinase (PI3K)/protein kinase B (AKT)-related microRNAs and mRNAs expressions in pancreatic tissues (Zhao et al, 2014;Mo et al, 2017;Yu et al, 2017). Another study also suggested that JTXK granule can regulate glycolipid metabolism in the liver tissue of diabetic mice (Yi et al, 2016).…”

Exosomes and miRNA-Loaded Biomimetic Nanovehicles, a Focus on Their Potentials Preventing Type-2 Diabetes Linked to Metabolic Syndrome

“…The 18 nucleosides in 5′ are identical to all family and constitute e form; the 3′ end of b is “GCAA,” of c “GU” and of d “A.” This miRNA does not harbor hexanucleotide element putatively facilitating addressing to nucleus ( 43 ). In addition, miR-320-5p has been reported only in diabetic mouse pancreatic tissue ( 40 ), no report in human. In rat, miR-320-3p is involved in embryo implantation ( 44 ) and in mouse is targeting heat-shock protein-20 (also hspb6) in cardiac ischemia/reperfusion injury ( 45 ) .…”

Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis

“…We identified strongly upregulated miR-320a in high GIP versus low GIP subjects. Transcriptomic data from mice pancreatic tissue point to miR-320 as the negative regulator of the mRNA associated with PI3K-Akt pathway, and hence disturbed nutrient metabolism and diabetes [78]. Recently, it has been documented that miR-320 inhibits SIRT1 expression via targeting the 3 UTR region of FoxM1 [79].…”