Sandalwood seed oil ameliorates hepatic insulin resistance by regulating the JNK/NF-κB inflammatory and PI3K/AKT insulin signaling pathways

2021 ◽  
Author(s):  
Huijun Zhang ◽  
Xiang Gao ◽  
Kelei Li ◽  
Yandi Liu ◽  
Dhanushka S. Hettiarachichi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Seed Oil ◽  
Insulin Signaling Pathway ◽  
Hepatic Insulin Resistance ◽  
Inflammatory Signaling

Sandalwood seed oil improved insulin resistance by activating the PI3K/AKT insulin signaling pathway and by down-regulating the JNK/NF-κB inflammatory signaling pathway in the liver.

scholarly journals NEFAs Influence the Inflammatory and Insulin Signaling Pathways Through TLR4 in Primary Calf Hepatocytes in vitro

2021 ◽  
Vol 8 ◽  
Author(s):  
Qinghua Deng ◽  
Liyin Du ◽  
Yuming Zhang ◽  
Guowen Liu
Keyword(s):  
Insulin Resistance ◽  
Energy Balance ◽  
Dairy Cows ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Inflammatory Signaling ◽  
Insulin Pathway

Transition dairy cows are often in a state of negative energy balance because of decreased dry matter intake and increased energy requirements, initiating lipid mobilization and leading to high serum β-hydroxybutyrate (BHBA) and non-esterified fatty acid (NEFAs) levels, which can induce ketosis and fatty liver in dairy cows. Inflammation and insulin resistance are also common diseases in the perinatal period of dairy cows. What is the relationship between negative energy balance, insulin resistance and inflammation in dairy cows? To study the role of non-esterified fatty acids in the nuclear factor kappa beta (NF-κB) inflammatory and insulin signaling pathways through Toll-like receptor 4 (TLR4), we cultured primary calf hepatocytes and added different concentrations of NEFAs to assess the mRNA and protein levels of inflammatory and insulin signaling pathways. Our experiments indicated that NEFAs could activate the NF-κB inflammatory signaling pathway and influence insulin resistance through TLR4. However, an inhibitor of TLR4 alleviated the inhibitory effects of NEFAs on the insulin pathway. In conclusion, all of these results indicate that high-dose NEFAs (2.4 mM) can activate the TLR4/NF-κB inflammatory signaling pathway and reduce the sensitivity of the insulin pathway through the TLR4/PI3K/AKT metabolic axis.

scholarly journals NEFAs Influence the NF-κB Inflammatory and Insulin Signaling Pathways Through TLR4 in Bovine Hepatocytes In Vitro

2021 ◽  
Author(s):  
Qinghua Deng ◽  
Liyin Du ◽  
Yuming Zhang ◽  
Guowen Liu
Keyword(s):  
Insulin Resistance ◽  
Energy Balance ◽  
Dairy Cows ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Inflammatory Signaling ◽  
Insulin Pathway

Abstract Dairy cows are often in a state of negative energy balance (NEB), because of decreased dry matter intake and increased energy requirements, initiating lipid mobilization and leading to high serum β-hydroxybutyrate and nonesterified fatty acid (NEFA) levels, which can induce ketosis and fatty liver in dairy cows. We all have known that inflammation and insulin resistance are also common diseases in perinatal period of dairy cows. So what is the relationship between negative energy balance, insulin resistance and inflammation in cow? In order to study the role of NEFAs in the NF-κB inflammatory and insulin signaling pathways through TLR4, we cultured bovine primary hepatocytes and added different concentrations of NEFAs to test the mRNA and protein levels of inflammatory and insulin signaling pathways. Our experiments indicated that NEFAs could activate the NF-κB inflammatory signaling pathway and influence insulin resistance through TLR4. However, an inhibitor of TLR4 alleviated the inhibitory effects of NEFAs on the insulin pathway. In conclusion, all of these results indicate that high-dose NEFAs can activate the TLR4/NF-κB inflammatory signaling pathway, and reduce the sensitivity of the insulin pathway through the TLR4/PI3K/AKT metabolic axis.

Identification of transcription factors MYC and C/EBPβ mediated regulatory networks in heart failure based on GEO dataset

2020 ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Hua Cao
Keyword(s):  
Heart Failure ◽  
Transcription Factors ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Regulatory Networks ◽  
Target Genes ◽  
Transcriptional Profiling ◽  
Insulin Signaling Pathway ◽  
Failing Heart

Abstract Background: Heart failure is one of leading cause of death worldwide. However, the transcriptional profiling of heart failure is unclear. Moreover, the signaling pathways and transcription factors involving the heart failure development also are largely unknown. Using published Gene Expression Omnibus (GEO) datasets, in the present study, we aim to comprehensively analyze the differentially expressed genes in failing heart tissues, and identified the critical signaling pathways and transcription factors involving heart failure development. Methods: The transcriptional profiling of heart failure was identified from previously published gene expression datasets deposited in GSE5406, GSE16499 and GSE68316. The enriched signaling pathways and transcription factors were analyzed using DAVID website and gene set enrichment analysis (GSEA) assay. The transcriptional networks were created by Cytoscape. Results: Compared with the normal heart tissues, 90 genes were particularly differentially expressed in failing heart tissues, and those genes were associated with multiple metabolism signaling pathways and insulin signaling pathway. Metabolism and insulin signaling pathway were both inactivated in failing heart tissues. Transcription factors MYC and C/EBPβ were both negatively associated with the expression profiling of failing heart tissues in GSEA assay. Moreover, compared with normal heart tissues, MYC and C/EBPβ were down regulated in failing heart tissues. Furthermore, MYC and C/EBPβ mediated downstream target genes were also decreased in failing heart tissues. MYC and C/EBPβ were positively correlated with each other. At last, we constructed MYC and C/EBPβ mediated regulatory networks in failing heart tissues, and identified the MYC and C/EBPβ target genes which had been reported involving the heart failure developmental progress. Conclusions: Our results suggested that metabolism pathways and insulin signaling pathway, transcription factors MYC and C/EBPβ played critical roles in heart failure developmental progress.

Duodenal-jejunal exclusion improves insulin resistance in type 2 diabetic rats by upregulating the hepatic insulin signaling pathway

Nutrition ◽  
2015 ◽  
Vol 31 (5) ◽  
pp. 733-739 ◽  
Author(s):  
Ze-Qiang Ren ◽  
Peng-Bo Zhang ◽  
Xiu-Zhong Zhang ◽  
Shou-Kun Chen ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Diabetic Rats ◽  
Insulin Signaling Pathway ◽  
Hepatic Insulin Signaling ◽  
Type 2 Diabetic

A novel PTP1B inhibitor extracted fromGanoderma lucidumameliorates insulin resistance by regulating IRS1-GLUT4 cascades in the insulin signaling pathway

2018 ◽  
Vol 9 (1) ◽  
pp. 397-406 ◽  
Author(s):  
Zhou Yang ◽  
Fan Wu ◽  
Yanming He ◽  
Qiang Zhang ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Insulin Signaling Pathway ◽  
Schematic Diagram ◽  
L6 Cells

A schematic diagram showing the IRS1-GLUT4 insulin signaling pathway influenced by PTP1B and FYGL in L6 cells.

scholarly journals 1197Identification of insulin signaling pathway-related circulating circRNAs as novel biomarkers of type 2 diabetes

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Yu-xiang Yan ◽  
Ya-Ke Lu ◽  
Xi Chu ◽  
Yue Sun ◽  
Jing Dong
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Akt Signaling ◽  
Insulin Signaling Pathway ◽  
Luciferase Reporter ◽  
Mirna Targets ◽  
Novel Biomarkers

Abstract Background The underlying molecular mechanism of type 2 diabetes (T2D) and insulin resistance is that abnormalities occur in the complex insulin signaling pathway. Circular RNAs (circRNAs) are involved in the development of diseases by regulating gene expression and become promising novel biomarkers for diseases. This study screened and validated the insulin signaling pathway-related circulating circRNAs, which are associated with T2D. Methods Based on circRNA microarray, candidate circRNAs involved in the insulin PI3K/Akt signaling pathway were selected and validated by RT-qPCR. The association between circRNAs and T2D and their clinical significance were further assessed by logistic regression model, correlation analysis and ROC curve in a large cohort. The miRNA targets of validated circRNAs was verified by dual-luciferase reporter assay. Results A total of 370 upregulated circRNAs and 180 downregulated circRNAs were differentially expressed between new T2D cases and controls. hsa_circ_0063425, hsa_circ_0056891 and hsa_circ_0104123 were selected as candidate circRNAs for validation. Low expressed circ_0063425 and hsa_circ_0056891 were independent predictors of T2D, impaired fasting glucose (IFG) and insulin resistance. The two-circRNA panel had a high diagnostic accuracy for discriminating T2D and IFG from healthy controls. miR-19a-3p and miR-1-3p were identified as the miRNA targets of hsa_circ_0063425 and hsa_circ_0056891, respectively. Significantly positive correlations were found between the expression levels of AKT and hsa_circ_0063425, PI3K and hsa_circ_0056891, in the total sample and subgroups stratified by glucose levels. Conclusion hsa_circ_0063425 and hsa_circ_0056891 are valuable circulating biomarkers for early detection of T2D, which may be involved in regulation of PI3K/AKT signaling. Key messages Insulin signaling pathway-related circulating circRNAs was identification as novel biomarkers of type 2 diabetes. Keywords circRNA; type 2 diabetes; insulin signaling; biomarker.

scholarly journals Intracellular pH Regulation of Skeletal Muscle in the Milieu of Insulin Signaling

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2910
Author(s):  
Dheeraj Kumar Posa ◽  
Shahid P. Baba
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Signaling Pathway ◽  
Intracellular Ph ◽  
Cross Talk ◽  
Insulin Signaling ◽  
Insulin Signaling Pathway ◽  
Glycolytic Pathway ◽  
Insulin Responses

Type 2 diabetes (T2D), along with obesity, is one of the leading health problems in the world which causes other systemic diseases, such as cardiovascular diseases and kidney failure. Impairments in glycemic control and insulin resistance plays a pivotal role in the development of diabetes and its complications. Since skeletal muscle constitutes a significant tissue mass of the body, insulin resistance within the muscle is considered to initiate the onset of diet-induced metabolic syndrome. Insulin resistance is associated with impaired glucose uptake, resulting from defective post-receptor insulin responses, decreased glucose transport, impaired glucose phosphorylation, oxidation and glycogen synthesis in the muscle. Although defects in the insulin signaling pathway have been widely studied, the effects of cellular mechanisms activated during metabolic syndrome that cross-talk with insulin responses are not fully elucidated. Numerous reports suggest that pathways such as inflammation, lipid peroxidation products, acidosis and autophagy could cross-talk with insulin-signaling pathway and contribute to diminished insulin responses. Here, we review and discuss the literature about the defects in glycolytic pathway, shift in glucose utilization toward anaerobic glycolysis and change in intracellular pH [pH]i within the skeletal muscle and their contribution towards insulin resistance. We will discuss whether the derangements in pathways, which maintain [pH]i within the skeletal muscle, such as transporters (monocarboxylate transporters 1 and 4) and depletion of intracellular buffers, such as histidyl dipeptides, could lead to decrease in [pH]i and the onset of insulin resistance. Further we will discuss, whether the changes in [pH]i within the skeletal muscle of patients with T2D, could enhance the formation of protein aggregates and activate autophagy. Understanding the mechanisms by which changes in the glycolytic pathway and [pH]i within the muscle, contribute to insulin resistance might help explain the onset of obesity-linked metabolic syndrome. Finally, we will conclude whether correcting the pathways which maintain [pH]i within the skeletal muscle could, in turn, be effective to maintain or restore insulin responses during metabolic syndrome.

Sign in / Sign up

Export Citation Format

Share Document