Metabolic Role of PTEN in Insulin Signaling and Resistance

Li, Yu Zhe; Cristofano, Antonio Di; Woo, Minna

doi:10.1101/cshperspect.a036137

Cited by 31 publications

(28 citation statements)

References 122 publications

(131 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…47 This pathway is also a very important signaling pathway for regulating glucose homeostasis and its activation can reduce circulating glucose concentration. 48 A relatively higher activity of PI3K-Akt pathway in cases compared to controls can potentially induce a metabolic phenotype similar with that observed in the present study, that is, higher lipids (possibly because of higher endogenous biosynthesis) and uric acids (because of lower urinary excretion) and lower glucose in fasting plasma. Higher activity of PI3K-Akt singling is also etiologically important in the development of PCa.…”

Section: Other Studiessupporting

confidence: 81%

Identification of prediagnostic metabolites associated with prostate cancer risk by untargeted mass spectrometry‐based metabolomics: A case‐control study nested in the Northern Sweden Health and Disease Study

Östman

Pinto

Ebbels

et al. 2022

Intl Journal of Cancer

View full text Add to dashboard Cite

Prostate cancer (PCa) is the most common cancer form in males in many European and American countries, but there are still open questions regarding its etiology.Untargeted metabolomics can produce an unbiased global metabolic profile, with the opportunity for uncovering new plasma metabolites prospectively associated with risk of PCa, providing insights into disease etiology. We conducted a prospective untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis using prediagnostic fasting plasma samples from 752 PCa case-control pairs nested within the Northern Sweden Health and Disease Study (NSHDS). The pairs were matched by age, BMI, and sample storage time. Discriminating features were identified by a combination of orthogonal projection to latent structures-effect projections (OPLS-EP) and Wilcoxon signed-rank tests. Their prospective associations with PCa risk were investigated by conditional logistic regression. Subgroup analyses based on stratification by disease aggressiveness and baseline age were also conducted. Various free fatty acids and phospholipids were positively associated with overall risk of PCa and in various stratification subgroups. Aromatic amino acids were positively associated with overall risk of PCa. Uric acid was positively, and glucose negatively, associated with risk of PCa in the older subgroup. This is the largest untargeted LC-MS based metabolomics study to date on plasma metabolites prospectively associated with risk of developing PCa. Different subgroups of disease aggressiveness and baseline age showed different associations with metabolites. The findings suggest that shifts in plasma concentrations of metabolites in lipid, aromatic amino

show abstract

Section: Other Studiessupporting

confidence: 81%

Identification of prediagnostic metabolites associated with prostate cancer risk by untargeted mass spectrometry‐based metabolomics: A case‐control study nested in the Northern Sweden Health and Disease Study

Östman

Pinto

Ebbels

et al. 2022

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…IR always involves disturbances in intracellular insulin signaling [92]. It commonly concerns decreased activity or expression of molecules involved in signal transduction (INSR, IRS-1, GLUT-4), decreased expression / translocation of GLUT-4, or increased expression/activity of antagonists of PI3K/AKT pathway, e.g., phosphatase and tensin homolog (PTEN), and polypyrimidine tract binding protein-1 (PTP1B) [93][94][95][96]. The impaired signaling of insulin demands increased concentrations of insulin (hyperinsulinemia).…”

Section: Insulin Resistance Hyperglycemia and Oxidative Stressmentioning

confidence: 99%

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Włodarski

Strycharz

Wróblewski

et al. 2020

IJMS

View full text Add to dashboard Cite

Oxidative stress (OxS) is the cause and the consequence of metabolic syndrome (MetS), the incidence and economic burden of which is increasing each year. OxS triggers the dysregulation of signaling pathways associated with metabolism and epigenetics, including microRNAs, which are biomarkers of metabolic disorders. In this review, we aimed to summarize the current knowledge regarding the interplay between microRNAs and OxS in MetS and its components. We searched PubMed and Google Scholar to summarize the most relevant studies. Collected data suggested that different sources of OxS (e.g., hyperglycemia, insulin resistance (IR), hyperlipidemia, obesity, proinflammatory cytokines) change the expression of numerous microRNAs in organs involved in the regulation of glucose and lipid metabolism and endothelium. Dysregulated microRNAs either directly or indirectly affect the expression and/or activity of molecules of antioxidative signaling pathways (SIRT1, FOXOs, Keap1/Nrf2) along with effector enzymes (e.g., GPx-1, SOD1/2, HO-1), ROS producers (e.g., NOX4/5), as well as genes of numerous signaling pathways connected with inflammation, insulin sensitivity, and lipid metabolism, thus promoting the progression of metabolic imbalance. MicroRNAs appear to be important epigenetic modifiers in managing the delicate redox balance, mediating either pro- or antioxidant biological impacts. Summarizing, microRNAs may be promising therapeutic targets in ameliorating the repercussions of OxS in MetS.

show abstract

“…The findings showed that PTEN exhibited similar changes to those of G6PC2 following the administration of differentially sourced exosomes. Studies report that PTEN impairs insulin signaling and induces insulin resistance during the pathogenesis of type 2 diabetes [ 49 ]. Metabolic organs, including the liver and muscle, exhibit significant increase in insulin sensitivity and glucose metabolism after the knockout of PTEN [ 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomal Circular RNA hsa_circ_0046060 of Umbilical Cord Mesenchymal Stromal Cell Ameliorates Glucose Metabolism and Insulin Resistance in Gestational Diabetes Mellitus via the miR-338-3p/G6PC2 Axis

Cao

Zhang

et al. 2022

International Journal of Endocrinology

View full text Add to dashboard Cite

Background. Impaired glucose metabolism and insulin sensitivity have been linked to the pathogenesis of gestational diabetes mellitus (GDM). Exosomes secreted by the umbilical cord mesenchymal stromal cells (UMSCs) and circular RNAs (circRNAs) derived from exosomes have been shown to be associated with the progression of GDM-related complications. Methods. UMSCs were isolated from umbilical cords and identified through flow cytometry. Exosomes were isolated from UMSCs and were then characterized. The expression levels of RNA of hsa_circ_0046060, mmu_circ_0002819, and miR-338-3p were determined by quantitative real-time polymerase chain reaction (RT-qPCR). The intracellular glucose intake and glycogen content were measured using a High Sensitivity Glucose Assay Kit and Glycogen Assay Kit, respectively. Bioinformatics analysis and luciferase reporter assay were used to validate interactions among hsa_circ_0046060, miR-338-3p, and G6PC2. The expression of insulin receptor substrate-1 (IRS-1) and its phosphorylated form, (p-IRS-1), as well as G6PC2, was determined through western blotting. Results. UMSCs and exosomes were successfully isolated and identified. The upregulation of hsa_circ_0046060 decreased the intracellular glucose content in L-02 cells (43.45 vs. 16.87 pM/mg, P = 0.0002 ), whereas shRNA-mediated downregulation reversed this effect (16.87 vs. 33.16 pM/mg, P = 0.0011 ). Mmu_circ_0002819 in mice aggravated dysregulated glucose metabolism (49.88 vs. 21.69 pM/mg, P = 0.0031 ) and insulin sensitivity (0.20 vs. 0.11 mg/mL, P = 0.03 ) in GDM mice, which was abrogated by the knockdown of mmu_circ_0002819. The results of luciferase reporter assay revealed that miR-338-3p and G6PC2 were the potential targets of has_circ_0046060. Western blotting results showed that the reduced activation of IRS-1 induced by GDM (1.25 vs. 0.54, P = 0.0001 ) could be rescued by the administration of si-circ-G-UMSC-EXOs (0.54 vs. 1.17, P = 0.0001 ). Conclusion. Taken together, the inhibition of hsa_circ_0046060 expression in exosomes from GDM-derived UMSCs can alleviate GDM by reversing abnormal glucose metabolism and insulin resistance in vivo and in vitro.

show abstract

Metabolic Role of PTEN in Insulin Signaling and Resistance

Cited by 31 publications

References 122 publications

Identification of prediagnostic metabolites associated with prostate cancer risk by untargeted mass spectrometry‐based metabolomics: A case‐control study nested in the Northern Sweden Health and Disease Study

Identification of prediagnostic metabolites associated with prostate cancer risk by untargeted mass spectrometry‐based metabolomics: A case‐control study nested in the Northern Sweden Health and Disease Study

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Exosomal Circular RNA hsa_circ_0046060 of Umbilical Cord Mesenchymal Stromal Cell Ameliorates Glucose Metabolism and Insulin Resistance in Gestational Diabetes Mellitus via the miR-338-3p/G6PC2 Axis

Contact Info

Product

Resources

About