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.

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

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.

scholarly journals Obesity induced by high-fat diet promotes insulin resistance in the ovary

2010 ◽  
Vol 206 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Eliana H Akamine ◽  
Anderson C Marçal ◽  
João Paulo Camporez ◽  
Mara S Hoshida ◽  
Luciana C Caperuto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Insulin Signaling Pathway ◽  
Female Rats ◽  
High Fat ◽  
Obese Rats

Besides the effects on peripheral energy homeostasis, insulin also has an important role in ovarian function. Obesity has a negative effect on fertility, and may play a role in the development of the polycystic ovary syndrome in susceptible women. Since insulin resistance in the ovary could contribute to the impairment of reproductive function in obese women, we evaluated insulin signaling in the ovary of high-fat diet-induced obese rats. Female Wistar rats were submitted to a high-fat diet for 120 or 180 days, and the insulin signaling pathway in the ovary was evaluated by immunoprecipitation and immunoblotting. At the end of the diet period, we observed insulin resistance, hyperinsulinemia, an increase in progesterone serum levels, an extended estrus cycle, and altered ovarian morphology in obese female rats. Moreover, in female obese rats treated for 120 days with the high-fat diet, the increase in progesterone levels occurred together with enhancement of LH levels. The ovary from high-fat-fed female rats showed a reduction in the insulin receptor substrate/phosphatidylinositol 3-kinase/AKT intracellular pathway, associated with an increase in FOXO3a, IL1B, and TNFα protein expression. These changes in the insulin signaling pathway may have a role in the infertile state associated with obesity.

scholarly journals The Hepatitis C Virus Modulates Insulin Signaling Pathway In Vitro Promoting Insulin Resistance

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47904 ◽  
Author(s):  
José A. del Campo ◽  
Marta García-Valdecasas ◽  
Lourdes Rojas ◽  
Ángela Rojas ◽  
Manuel Romero-Gómez
Keyword(s):  
Insulin Resistance ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Insulin Signaling Pathway

scholarly journals Blood Orange Juice Intake Modulates the Expression of miR-126–3p and let-7f-5p in PBMC of Overweight and Insulin Resistance Women

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 936-936
Author(s):  
Vinícius Cooper Capetini ◽  
Bruna Jardim Quintanilha ◽  
Geni Rodrigues Sampaio ◽  
Frederico Moraes Ferreira ◽  
Marcelo Rogero
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Orange Juice ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Insulin Signaling Pathway ◽  
Model Assessment ◽  
Blood Orange

Abstract Objectives To investigate the effect of chronic blood orange juice intake on the microRNA profile in peripheral blood mononuclear cells (PBMC) of overweight and insulin resistance women. Methods Interventional and chronic study with women (n = 8) aged 18 to 40 years, diagnosed with overweight [body mass index (BMI) 25–29.9 kg/m2] and insulin resistance [homeostatic model assessment insulin resistance (HOMA-IR) index >2,71]. For four weeks, the volunteers ingested 500 mL/day of blood orange juice (Moro variety), with blood samples collected at baseline and four weeks after the beginning of drink ingestion. Evaluation of the expression of 137 microRNAs in PBMC was performed by real-time polymerase chain reaction (PCR). Results Blood orange juice intake decreased the expression of miR-126-3p (p = 0.004) and let-7f-5p (p = 0.005) in PBMC. These microRNAs are involved in suppressing the synthesis of several proteins of the insulin signaling pathway. Insulin receptor substrates (IRS) 1 and 2 were identified as target genes of mir-126. Insulin-like growth factor 1 receptor (IGF1R), insulin receptor (INSR), IRS2, phosphatidylinositol-3-kinase interacting protein 1 (PIK3IP1), and protein kinase B/Akt 2 (AKT2) were identified as target genes of let-7f. Conclusions Blood orange juice, rich in vitamin C, flavonoids, and anthocyanins, downregulates the expression of microRNA involved in impairing the insulin signaling pathway. Funding Sources Food Research Center (FoRC), São Paulo Research Foundation (FAPESP)

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