Phosphorylation of protein kinase B, the key enzyme in insulin-signaling cascade, is enhanced in linoleic and arachidonic acid–treated HT29 and HepG2 cells

Nutrition ◽  
2019 ◽  
Vol 57 ◽  
pp. 52-58 ◽  
Author(s):  
Katia Mariniello ◽  
Yoeju Min ◽  
Kebreab Ghebremeskel
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase ◽  
Insulin Signaling ◽  
Hepg2 Cells ◽  
Protein Kinase B ◽  
Signaling Cascade ◽  
Key Enzyme

Exercise-associated differences in an array of proteins involved in signal transduction and glucose transport

2001 ◽  
Vol 90 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Mei Yu ◽  
Eva Blomstrand ◽  
Alexander V. Chibalin ◽  
Harriet Wallberg-Henriksson ◽  
Juleen R. Zierath ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Cascade ◽  
Vastus Lateralis Muscle ◽  
Glut 4 ◽  
Mitogen Activated Protein ◽  
Kinase Expression

Vastus lateralis muscle biopsies were obtained from endurance-trained (running ∼50 km/wk) and untrained (no regular physical exercise) men, and the expression of an array of insulin-signaling intermediates was determined. Expression of insulin receptor and insulin receptor substrate-1 and -2 was decreased 44% ( P < 0.05), 57% ( P < 0.001), and 77% ( P < 0.001), respectively, in trained vs. untrained muscle. The downstream signaling target, Akt kinase, was not altered in trained subjects. Components of the mitogenic signaling cascade were also assessed. Extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase expression was 190% greater ( P < 0.05), whereas p38 mitogen-activated protein kinase expression was 32% lower ( P < 0.05), in trained vs. untrained muscle. GLUT-4 protein expression was twofold higher ( P < 0.05), and the GLUT-4 vesicle-associated protein, the insulin-regulated aminopeptidase, was increased 4.7-fold ( P < 0.05) in trained muscle. In conclusion, the expression of proteins involved in signal transduction is altered in skeletal muscle from well-trained athletes. Downregulation of early components of the insulin-signaling cascade may occur in response to increased insulin sensitivity associated with endurance training.

scholarly journals Glycyrrhetinic Acid Improves Insulin-Response Pathway by Regulating the Balance between the Ras/MAPK and PI3K/Akt Pathways

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 604 ◽  
Author(s):  
Yuan Zhang ◽  
Shengnan Yang ◽  
Man Zhang ◽  
Zhihua Wang ◽  
Xin He ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Insulin Signaling ◽  
Hepg2 Cells ◽  
Mapk Pathway ◽  
Insulin Response ◽  
Glycyrrhetinic Acid ◽  
Intracellular Enzyme ◽  
Target Proteins ◽  
Iκb Kinase

Glycyrrhetinic acid (GA), a bioactive component in the human diet, has been reported to improve hyperglycemia, dyslipidemia, insulin resistance and obesity in rats with metabolic syndrome. However, GA-specific target proteins and the mechanisms involved in the downstream signaling and cross-talk to improve insulin sensitivity have not been fully elucidated. In this study, the potential targets of GA were identified by chemical proteomics strategies using serial GA probes for target fishing and cell molecular imaging. Intracellular enzyme activity evaluation and insulin resistance models were used for validating the function of the target proteins on the downstream insulin signaling pathways. Collectively, our data demonstrate that GA improved the insulin-responsive pathway and glucose consumption levels via multiple diabetogenic factors that activated the insulin signaling pathway in HepG2 cells. GA improved Glucose transporter 4(GLUT4) expression by targeting the Ras protein to regulate the mitogen-activated protein kinase (MAPK) pathway. GA exhibited a strong inhibitory effect on IRS1ser307 phosphorylation in cells treated with the Protein kinase C (PKC) activator Phorbol 12-myristate 13-acetate (PMA.) Consistently, IRS1ser307 phosphorylation was also inhibited by GA in Free fatty acid (FFA)-treated HepG2 cells. GA also inhibited the PMA-induced phosphorylation of IκB kinase α/β (IKKα/β), c-Jun N-terminal kinase (JNK) and p38 proteins (P38), suggesting that IKKα/β, JNK and P38 activation is dependent on PKC activity.

scholarly journals Phosphorylation and Activation of Heart 6-Phosphofructo-2-kinase by Protein Kinase B and Other Protein Kinases of the Insulin Signaling Cascades

1997 ◽  
Vol 272 (28) ◽  
pp. 17269-17275 ◽  
Author(s):  
Johan Deprez ◽  
Didier Vertommen ◽  
Dario R. Alessi ◽  
Louis Hue ◽  
Mark H. Rider
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Insulin Signaling ◽  
Protein Kinase B ◽  
Signaling Cascades

scholarly journals Both Saturated and n-6 Polyunsaturated Fat Diets Reduce Phosphorylation of Insulin Receptor Substrate-1 and Protein Kinase B in Muscle during the Initial Stages of in Vivo Insulin Stimulation

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5596-5603 ◽  
Author(s):  
Georgia Frangioudakis ◽  
Ji-Ming Ye ◽  
Gregory J. Cooney
Keyword(s):  
Protein Kinase ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
Protein Kinase B ◽  
Insulin Receptor Substrate ◽  
Polyunsaturated Fat ◽  
Insulin Stimulation ◽  
High Fat ◽  
Fat Diets

Our aim was to determine the importance of changes in phosphorylation of key insulin signaling intermediates in the insulin resistance observed in skeletal muscle of rats fed diets high in saturated or n-6 polyunsaturated fat. We used phospho-specific antibodies to measure the time course of phosphorylation of key components of the insulin signaling pathway by immunoblotting during the initial stages of a physiological elevation in the circulating insulin concentration. The phosphorylation of insulin receptor at Tyr1162/1163 (IR Tyr1162/1163) increased over 20 min of insulin infusion, whereas the downstream phosphorylation of insulin receptor substrate-1 Tyr612 (IRS-1 Tyr612) peaked at 5 min and declined thereafter. Interestingly, phosphorylation of IRS-1 at Tyr895 continued to increase over the 20-min period, and protein kinase B (PKB) phosphorylation at Ser473 reached a plateau by 5 min, demonstrating that different profiles of phosphorylation are involved in transmission of the insulin signal despite a constant level of insulin stimulation. In muscle from rats fed high n-6 polyunsaturated or saturated fat diets, however, there was no insulin-stimulated increase in IRS-1 Tyr612 phosphorylation and a temporal difference in PKB Ser473 phosphorylation despite no difference in IR Tyr1162/1163 phosphorylation, IRS-1 Tyr895 phosphorylation, and ERK phosphorylation. These results demonstrate that under conditions of increased insulin, similar to those used to assess insulin action in vivo, chronic high-fat feeding impairs insulin signal transduction related to glucose metabolism at the level of IRS-1 Tyr612 and PKB Ser473 and that these effects are independent of the type of fat used in the high-fat diet.

scholarly journals Interleukin-1β-Induced Insulin Resistance in Adipocytes through Down-Regulation of Insulin Receptor Substrate-1 Expression

Endocrinology ◽  
2007 ◽  
Vol 148 (1) ◽  
pp. 241-251 ◽  
Author(s):  
Jennifer Jager ◽  
Thierry Grémeaux ◽  
Mireille Cormont ◽  
Yannick Le Marchand-Brustel ◽  
Jean-François Tanti
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Protein Kinase B ◽  
Transcriptional Level ◽  
Insulin Receptor Substrate ◽  
Down Regulation ◽  
Glut 4

Inflammation is associated with obesity and insulin resistance. Proinflammatory cytokines produced by adipose tissue in obesity could alter insulin signaling and action. Recent studies have shown a relationship between IL-1β level and metabolic syndrome or type 2 diabetes. However, the ability of IL-1β to alter insulin signaling and action remains to be explored. We demonstrated that IL-1β slightly increased Glut 1 translocation and basal glucose uptake in 3T3-L1 adipocytes. Importantly, we found that prolonged IL-1β treatment reduced the insulin-induced glucose uptake, whereas an acute treatment had no effect. Chronic treatment with IL-1β slightly decreased the expression of Glut 4 and markedly inhibited its translocation to the plasma membrane in response to insulin. This inhibitory effect was due to a decrease in the amount of insulin receptor substrate (IRS)-1 but not IRS-2 expression in both 3T3-L1 and human adipocytes. The decrease in IRS-1 amount resulted in a reduction in its tyrosine phosphorylation and the alteration of insulin-induced protein kinase B activation and AS160 phosphorylation. Pharmacological inhibition of ERK totally inhibited IL-1β-induced down-regulation of IRS-1 mRNA. Moreover, IRS-1 protein expression and insulin-induced protein kinase B activation, AS160 phosphorylation, and Glut 4 translocation were partially recovered after treatment with the ERK inhibitor. These results demonstrate that IL-1β reduces IRS-1 expression at a transcriptional level through a mechanism that is ERK dependent and at a posttranscriptional level independently of ERK activation. By targeting IRS-1, IL-1β is capable of impairing insulin signaling and action, and could thus participate in concert with other cytokines, in the development of insulin resistance in adipocytes.

scholarly journals Inhibitory effect of hyperglycemia on insulin-induced Akt/protein kinase B activation in skeletal muscle

2001 ◽  
Vol 280 (5) ◽  
pp. E816-E824 ◽  
Author(s):  
Akira Oku ◽  
Masao Nawano ◽  
Kiichiro Ueta ◽  
Takuya Fujita ◽  
Itsuro Umebayashi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Soleus Muscle ◽  
Insulin Signaling ◽  
Skeletal Muscles ◽  
Glucose Transporter ◽  
Protein Kinase B ◽  
Diabetic Rats

To determine the molecular mechanism underlying hyperglycemia-induced insulin resistance in skeletal muscles, postreceptor insulin-signaling events were assessed in skeletal muscles of neonatally streptozotocin-treated diabetic rats. In isolated soleus muscle of the diabetic rats, insulin-stimulated 2-deoxyglucose uptake, glucose oxidation, and lactate release were all significantly decreased compared with normal rats. Similarly, insulin-induced phosphorylation and activation of Akt/protein kinase B (PKB) and GLUT-4 translocation were severely impaired. However, the upstream signal, including phosphorylation of the insulin receptor (IR) and insulin receptor substrate (IRS)-1 and -2 and activity of phosphatidylinositol (PI) 3-kinase associated with IRS-1/2, was enhanced. The amelioration of hyperglycemia by T-1095, a Na+-glucose transporter inhibitor, normalized the reduced insulin sensitivity in the soleus muscle and the impaired insulin-stimulated Akt/PKB phosphorylation and activity. In addition, the enhanced PI 3-kinase activation and phosphorylation of IR and IRS-1 and -2 were reduced to normal levels. These results suggest that sustained hyperglycemia impairs the insulin-signaling steps between PI 3-kinase and Akt/PKB, and that impaired Akt/PKB activity underlies hyperglycemia-induced insulin resistance in skeletal muscle.

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