scholarly journals Chronic and Intermittent Hyperglycemia Modulates Expression of Key Molecules of PI3K/AKT Pathway in Differentiating Human Visceral Adipocytes

2021 ◽  
Vol 22 (14) ◽  
pp. 7712
Author(s):  
Ewa Świderska ◽  
Justyna Strycharz ◽  
Adam Wróblewski ◽  
Piotr Czarny ◽  
Janusz Szemraj ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
High Glucose ◽  
Insulin Signaling Pathway ◽  
Akt Pathway ◽  
Maturation Stage ◽  
Culture Stage ◽  
Differentiation And Proliferation ◽  
The Impact

Background: Due to its prominence in the regulation of metabolism and inflammation, adipose tissue is a major target to investigate alterations in insulin action. This hormone activates PI3K/AKT pathway which is essential for glucose homeostasis, cell differentiation, and proliferation in insulin-sensitive tissues, like adipose tissue. The aim of this work was to evaluate the impact of chronic and intermittent high glucose on the expression of biomolecules of insulin signaling pathway during the differentiation and maturation of human visceral preadipocytes. Methods:Human visceral preadipocytes (HPA-V) cells were treated with high glucose (30mM)during the proliferation and/or differentiation and/or maturation stage. The level of mRNA (by Real-Time PCR) and protein (by Elisa tests) expression of IRS1, PI3K, PTEN, AKT2, and GLUT4 was examined after each culture stage. Furthermore, we investigated whether miR-29a-3p, miR-143-3p, miR-152-3p, miR-186-5p, miR-370-3p, and miR-374b-5p may affect the expression of biomolecules of the insulin signaling pathway. Results: Both chronic and intermittent hyperglycemia affects insulin signaling in visceral pre/adipocytes by upregulation of analyzed PI3K/AKT pathway molecules. Both mRNA and protein expression level is more dependent on stage-specific events than the length of the period of high glucose exposure. What is more, miRs expression changes seem to be involved in PI3K/AKT expression regulation in response to hyperglycemic stimulation.

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.

Role of PDK4 in insulin signaling pathway in periadrenal adipose tissue of pheochromocytoma patients

2020 ◽  
Vol 27 (10) ◽  
pp. 583-589
Author(s):  
Chunyan Wu ◽  
Huijian Zhang ◽  
Xiaochun Lin ◽  
Yanmei Zeng ◽  
Yudan Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Adrenal Adenoma ◽  
Stromal Vascular Fraction ◽  
Insulin Signaling Pathway ◽  
Pyruvate Dehydrogenase Kinase ◽  
Mrna Levels

Studies have shown that pheochromocytoma (PHEO) is associated with glucose intolerance and decreased insulin sensitivity. In adipocytes, pyruvate dehydrogenase kinase 4 (PDK4) is involved in glucose uptake. However, very little is known about the role of PDK4 in the insulin signaling pathway in the adipose tissue of PHEO patients. We analyzed the expression of adipokines, oxidative stress-related genes, PDK4, phosphorylated AMPK (pAMPK) and phosphorylated IRS1 (pIRS1) in the periadrenal adipose tissue (peri-A) of patients with PHEO and non-functioning adrenal adenoma (NFA). We also investigated the effects of epinephrine on PDK4, pAMPK and pIRS1 in human stromal vascular fraction (SVF) cells, mouse 3T3-L1 preadipocytes and brown preadipocytes. PHEO patients had higher mRNA levels of PGC1α, C/EBPα, C/EBPβ, COXII and AP2 and lower mRNA levels of PPARγ in their peri-A than NFA patients. Decreased pAMPK and increased PDK4 and pIRS1 were observed in the peri-A of PHEO patients. PHEO patients also had significantly higher NOX4 protein expression and lower Nrf2 and HO-1 protein expression in their peri-A than NFA patients. In vitro, epinephrine treatment upregulated PDK4 expression, inhibited AMPK phosphorylation and enhanced IRS1 phosphorylation. The knockdown of PDK4 by siRNA upregulated pAMPK and downregulated pIRS1. In conclusion, PDK4 may play an essential role in hypercatecholamine-induced insulin resistance in the periadrenal adipose tissues of PHEO patients.

scholarly journals Chronic subordination stress selectively downregulates the insulin signaling pathway in liver and skeletal muscle but not in adipose tissue of male mice

Stress ◽  
2016 ◽  
Vol 19 (2) ◽  
pp. 214-224 ◽  
Author(s):  
Valentina Sanghez ◽  
Cankut Cubuk ◽  
Patricia Sebastián-Leon ◽  
Stefania Carobbio ◽  
Joaquin Dopazo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Insulin Signaling Pathway ◽  
Male Mice

Leucine reduces the duration of insulin-induced PI 3-kinase activity in rat skeletal muscle

2005 ◽  
Vol 288 (1) ◽  
pp. E86-E91 ◽  
Author(s):  
Jamie I. Baum ◽  
Jason C. O'Connor ◽  
Jennifer E. Seyler ◽  
Tracy G. Anthony ◽  
Gregory G. Freund ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Translation Initiation ◽  
Insulin Signaling ◽  
Kinase Activity ◽  
Insulin Signaling Pathway ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
The Impact

Leucine (Leu) is known to stimulate translation initiation of protein synthesis at mammalian target of rapamycin (mTOR) in the insulin signaling pathway. However, potential feedback from mTOR to upstream aspects of the insulin signaling pathway remains controversial. This study evaluates the impact of a physiological oral dose of Leu and/or carbohydrate (CHO) on upstream elements of the insulin signaling pathway using phosphatidylinositol 3-kinase (PI 3-kinase) activity and glucose uptake as markers for insulin sensitivity and glucose homeostasis. Rats (∼200 g) were fasted 12 h and administered oral doses of CHO (1.31 g glucose, 1.31 g sucrose), Leu (270 mg), or CHO plus Leu. Animals were killed at 15, 30, 60, and 90 min after treatment. Plasma and gastrocnemius muscles were collected for analyses. Treatments were designed to produce elevated blood glucose and insulin with basal levels of Leu (CHO); elevated Leu with basal levels of glucose and insulin (Leu); or a combined increase of glucose, insulin, and Leu (CHO + Leu). The CHO treatment stimulated PI 3-kinase activity and glucose uptake with no effect on the downstream translation initiation factor eIF4E. Leu alone stimulated the release of the translation initiation factor eIF4E from 4E-BP1 with no effects on PI 3-kinase activity or glucose uptake. The CHO + Leu treatment reduced the magnitude and duration of the PI 3-kinase response but maintained glucose uptake similar to the CHO treatment and eIF4E levels similar to the Leu treatment. These findings demonstrate that Leu reduces insulin-stimulated PI 3-kinase activity while increasing downstream translation initiation and with no effect on net glucose transport in skeletal muscle.

scholarly journals Differential effect of long-term leucine supplementation on skeletal muscle and adipose tissue in old rats: an insulin signaling pathway approach

AGE ◽  
2011 ◽  
Vol 34 (2) ◽  
pp. 371-387 ◽  
Author(s):  
Gilbert Zeanandin ◽  
Michèle Balage ◽  
Stéphane M. Schneider ◽  
Joëlle Dupont ◽  
Xavier Hébuterne ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Differential Effect ◽  
Insulin Signaling Pathway ◽  
Leucine Supplementation ◽  
Old Rats

scholarly journals Down-regulation of the insulin signaling pathway by SHC may correlate with congenital heart disease in Chinese populations

2020 ◽  
Vol 134 (3) ◽  
pp. 349-358 ◽  
Author(s):  
Zhiling Luo ◽  
Longjiang Xu ◽  
Jiang Lu ◽  
Yan Shen ◽  
Yongyan Tang ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
High Glucose ◽  
Heart Development ◽  
Congenital Heart ◽  
Insulin Signaling Pathway ◽  
Right Atrial ◽  
Congenital Defects

Abstract Background/Aims: Congenital heart disease (CHD) is one of the most common and severe congenital defects. The incidence of fetal cardiac malformation is increased in the context of maternal gestational diabetes mellitus (GDM). Therefore, we wanted to determine whether abnormalities in the insulin signaling pathway are associated with the occurrence of nonsyndromic CHD (ns-CHD). Methods: We used digital gene expression profiling (DGE) of right atrial myocardial tissue samples from eight ns-CHD patients and four controls. The genes potentially associated with CHD were validated by real-time fluorescence quantitative PCR analysis of right atrial myocardial tissues from 37 patients and 10 controls and the H9C2 cell line. Results: The results showed that the insulin signaling pathway, which is mediated by the SHC gene family, was inhibited in the ns-CHD patients. The expression levels of five genes (PTPRF, SHC4, MAP2K2, MKNK2, and ELK1) in the pathway were significantly down-regulated in the patients’ atrial tissues (P<0.05 for all). In vitro, the H9C2 cells cultured in high glucose (33 mmol/l) expressed less SHC4, MAP2K2, and Elk-1 than those cultured in low glucose (25 mmol/l). Furthermore, the high glucose concentration down-regulated the 25 genes associated with blood vessel development based on Gene Ontology (GO) term enrichment analyses of RNA-seq data. Conclusion: We considered that changes in the insulin signaling pathway mediated by SHC might be involved in the heart development process. This mechanism might account for the increase in the incidence of fetal cardiac malformations in the context of GDM.

Virilizing doses of testosterone decrease circulating insulin levels and differentially regulate insulin signaling in liver and adipose tissue of females

2021 ◽  
Author(s):  
Kadden H Kothmann ◽  
Victoria Jacobsen ◽  
Emily Laffitte ◽  
Corinne Bromfield ◽  
Matthew Grizzaffi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Corn Oil ◽  
Serum Insulin ◽  
Serum Testosterone ◽  
Insulin Signaling Pathway ◽  
Insulin Levels ◽  
Transgender Men

Transgender men undergoing hormone therapy are at risk for insulin resistance. However, how virilizing testosterone therapy affects serum insulin and peripheral insulin sensitivity in transgender men is unknown. This study assessed the effect of acute, virilizing testosterone on serum insulin concentrations and insulin signaling in liver, skeletal muscle, and white adipose tissue (WAT) of female pigs as a translational model for transgender men. Females received three doses of intramuscular testosterone cypionate (TEST females; 50 mg/day/pig) or corn oil (control) spaced six days apart starting on the day of estrus (D0). Fasting blood was collected on D0, 3, 5, 11, and 13 and females were euthanized on D13. On D13, TEST females had virilizing concentrations of serum testosterone with normal concentrations of serum estradiol. Virilizing serum testosterone concentrations (D13) were associated with decreased serum insulin and C-peptide concentrations. Blood glucose and serum glycerol concentrations were not altered by testosterone. Virilizing concentrations of testosterone down-regulated AR and ESR1 in subcutaneous (sc) WAT and upregulated transcript levels of insulin signaling pathway components in WAT and liver. At the protein level, virilizing testosterone concentrations were associated with increased PI3K 110α in liver and increased INSR and phospho(Ser256)-FOXO1 in visceral (v) WAT but decreased phospho(Ser473)-AKT in vWAT and scWAT. These results suggest that acute exposure to virilizing concentrations of testosterone suppresses circulating insulin levels and results in increased abundance of proteins in the insulin signaling pathway in liver and altered phosphorylation of key proteins in control of insulin sensitivity in WAT.

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