scholarly journals MicroRNA-506 modulates insulin resistance in human adipocytes by targeting S6K1 and altering the IRS1/PI3K/AKT insulin signaling pathway

2021 ◽  
Author(s):  
Feng-Yu Zhong ◽  
Jing Li ◽  
Yu-Mei Wang ◽  
Yao Chen ◽  
Jia Song ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Underlying Mechanism ◽  
Insulin Signaling Pathway ◽  
Akt Pathway ◽  
Public Health Issue ◽  
Pathway Activation ◽  
Candidate Target

AbstractThe incidence of obesity has increased rapidly, becoming a worldwide public health issue that involves insulin resistance. A growing number of recent studies have demonstrated that microRNAs play a significant role in controlling the insulin signaling network. For example, miR-506-3p expression has been demonstrated to correlate with insulin sensitivity; however, the underlying mechanism remains unknown. In this study, we found that miR-506-3p enhanced glucose uptake by 2-deoxy-D-glucose uptake assays and regulated the protein expression of key genes involved in the PI3K/AKT insulin signaling pathway including IRS1, PI3K, AKT, and GlUT4. We next predicted ribosomal protein S6 kinase B1 (S6K1) to be a candidate target of miR-506-3p by bioinformatics analysis and confirmed using dual-luciferase assays that miR-506-3p regulated S6K1 expression by binding to its 3′-UTR. Moreover, modulating S6K1 expression counteracted the effects of miR-506-3p on glucose uptake and PI3K/AKT pathway activation. In conclusion, miR-506-3p altered IR in adipocytes by regulating S6K1-mediated PI3K/AKT pathway activation. Taken together, these findings provide novel insights and potential targets for IR therapy.

scholarly journals Local Cortisol Elevation Contributes to Endometrial Insulin Resistance in Polycystic Ovary Syndrome

2018 ◽  
Vol 103 (7) ◽  
pp. 2457-2467 ◽  
Author(s):  
Jia Qi ◽  
Wangsheng Wang ◽  
Qinling Zhu ◽  
Yaqiong He ◽  
Yao Lu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Polycystic Ovary ◽  
Implantation Rate ◽  
Insulin Signaling Pathway ◽  
Ovary Syndrome

Abstract Context Endometrial insulin resistance (IR) may account for the endometrial dysfunction in polycystic ovary syndrome (PCOS). The underlying mechanism remains to be elucidated. Objective To investigate whether the abundance of 11β-hydroxysteroid dehydrogenases (11β-HSDs) 1 and 2 and cortisol as well as the insulin signaling pathway are altered in PCOS endometrium and to clarify the relationship between endometrial IR and local cortisol. Design We measured cortisol and cortisone concentrations, 11β-HSD1 and 11β-HSD2, and core insulin signaling molecules in endometrial biopsies collected from non-PCOS and PCOS with or without IR patients on the seventh day after human chorionic gonadotropin injection. We also studied the effects of cortisol on glucose uptake and the insulin signaling pathway in primary cultured endometrial epithelial cells (EECs). Results The cortisol concentration was elevated, whereas 11β-HSD2 expression was diminished in endometrial biopsies obtained from PCOS with IR patients compared with those from non-PCOS and PCOS without IR patients. The implantation rate was relatively impaired and the endometrial insulin signaling pathway was defective in PCOS with IR patients. In addition, cortisol attenuated insulin-stimulated glucose uptake in EECs, which was mediated by inhibition of Akt phosphorylation and glucose transporter type 4 translocation via induction of phosphatase and tensin homolog deleted on chromosome ten (PTEN). Conclusions Decreased oxidation of cortisol and defects of insulin signaling in endometrium were observed in PCOS with IR patients. The excessive cortisol level, derived from the reduction of 11β-HSD2, might contribute to the development of endometrial IR by inhibiting the insulin signaling pathway via induction of PTEN expression in EECs.

scholarly journals Sphingomyelinase has an insulin-like effect on glucose transporter translocation in adipocytes

1998 ◽  
Vol 274 (5) ◽  
pp. R1446-R1453 ◽  
Author(s):  
T. S. David ◽  
P. A. Ortiz ◽  
T. R. Smith ◽  
J. Turinsky
Keyword(s):  
Plasma Membrane ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Insulin Signaling Pathway ◽  
Glut 1 ◽  
Glut 4 ◽  
Glut 4 Translocation

Rat epididymal adipocytes were incubated with 0, 0.1, and 1 mU sphingomyelinase/ml for 30 or 60 min, and glucose uptake and GLUT-1 and GLUT-4 translocation were assessed. Adipocytes exposed to 1 mU sphingomyelinase/ml exhibited a 173% increase in glucose uptake. Sphingomyelinase had no effect on the abundance of GLUT-1 in the plasma membrane of adipocytes. In contrast, 1 mU sphingomyelinase/ml increased plasma membrane content of GLUT-4 by 120% and produced a simultaneous decrease in GLUT-4 abundance in the low-density microsomal fraction. Sphingomyelinase had no effect on tyrosine phosphorylation of either the insulin receptor β-subunit or the insulin receptor substrate-1, a signaling molecule in the insulin signaling pathway. It is concluded that the incubation of adipocytes with sphingomyelinase results in insulin-like translocation of GLUT-4 to the plasma membrane and that this translocation does not occur via the activation of the initial components of the insulin signaling pathway.

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 Exercise-Induced Muscle Damage Impairs Insulin Signaling Pathway Associated With IRS-1 Oxidative Modification

2012 ◽  
pp. 81-88 ◽  
Author(s):  
W. AOI ◽  
Y. NAITO ◽  
H. TOKUDA ◽  
Y. TANIMURA ◽  
T. OYA-ITO ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Muscle Damage ◽  
Insulin Signaling ◽  
Acute Exercise ◽  
Insulin Signaling Pathway ◽  
Oxidative Modification ◽  
Whole Body ◽  
Strenuous Exercise

Strenuous exercise induces delayed-onset muscle damage including oxidative damage of cellular components. Oxidative stress to muscle cells impairs glucose uptake via disturbance of insulin signaling pathway. We investigated glucose uptake and insulin signaling in relation to oxidative protein modification in muscle after acute strenuous exercise. ICR mice were divided into sedentary and exercise groups. Mice in the exercise group performed downhill running exercise at 30 m/min for 30 min. At 24 hr after exercise, metabolic performance and insulin-signaling proteins in muscle tissues were examined. In whole body indirect calorimetry, carbohydrate utilization was decreased in the exercised mice along with reduction of the respiratory exchange ratio compared to the rested control mice. Insulin-stimulated uptake of 2-deoxy-[3H]glucose in damaged muscle was decreased after acute exercise. Tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidyl-3-kinase/Akt signaling were impaired by exercise, leading to inhibition of the membrane translocation of glucose transporter 4. We also found that acute exercise caused 4-hydroxy-nonenal modification of IRS-1 along with elevation of oxidative stress in muscle tissue. Impairment of insulin-induced glucose uptake into damaged muscle after strenuous exercise would be related to disturbance of insulin signal transduction by oxidative modification of IRS-1.

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