Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

Świderska, Ewa; Strycharz, Justyna; Wróblewski, Adam; Szemraj, Janusz; Drzewoski, Józef; Śliwińska, Agnieszka

doi:10.5772/intechopen.80402

Cited by 64 publications

(77 citation statements)

References 77 publications

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“…Insulin exerts its effects by binding to the insulin receptors, which induce the phosphorylation of the tyrosine residues on insulin receptor substrate (IRS) proteins. The phosphorylation of IRS results in the activation of Akt, which stimulates the translocation of glucose transporter (GLUT) from the cytosol to the cell membrane, facilitating glucose uptake into cells [26,27]. Previous studies indicated that treatment with 0.5-2.5 mM MGO resulted in insulin resistance in L6 cells and HepG2 cells [28,29].…”

Section: Discussionmentioning

confidence: 99%

Psoralea corylifoliaL. Seed Extract Attenuates Methylglyoxal-Induced Insulin Resistance by Inhibition of Advanced Glycation End Product Formation

Truong

Seo

Jun

2019

Oxidative Medicine and Cellular Longevity

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Accumulation of advanced glycation end products (AGEs) in the body has been implicated in the pathogenesis of metabolic conditions, such as diabetes mellitus. Methylglyoxal (MGO), a major precursor of AGEs, has been reported to induce insulin resistance in both in vitro and in vivo studies. Psoralea corylifolia seeds (PCS) have been used as a traditional medicine for several diseases, but their potential application in treating insulin resistance has not yet been evaluated. This study is aimed at investigating whether PCS extract could attenuate insulin resistance induced by MGO. Male C57BL/6N mice (6 weeks old) were administered 1% MGO in their drinking water for 18 weeks, and the PCS extract (200 or 500 mg/kg) was orally administered daily from the first day of the MGO administration. We observed that both 200 and 500 mg/kg PCS extract treatment significantly improved glucose tolerance and insulin sensitivity and markedly restored p-Akt and p-IRS1/2 expression in the livers of the MGO-administered mice. Additionally, the PCS extract significantly increased the phosphorylation of Akt and IRS-1/2 and glucose uptake in MGO-treated HepG2 cells. Further studies showed that the PCS extract inhibited MGO-induced AGE formation in the HepG2 cells and in the sera of MGO-administered mice. PCS extract also increased the expression of glyoxalase 1 (GLO1) in the liver tissue of MGO-administered mice. The PCS extract significantly decreased the phosphorylation of ERK, p38, and NF-κB and suppressed the mRNA expression of proinflammatory molecules including TNF-α and IL-1β and iNOS in MGO-administered mice. Additionally, we demonstrated that the PCS extract attenuated oxidative stress, as evidenced by the reduced ROS production in the MGO-treated cells and the enhanced expression of antioxidant enzymes in the liver of MGO-administered mice. Thus, PCS extract ameliorated the MGO-induced insulin resistance in HepG2 cells and in mice by reducing oxidative stress via the inhibition of AGE formation. These findings suggest the potential of PCS extract as a candidate for the prevention and treatment of insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Psoralea corylifoliaL. Seed Extract Attenuates Methylglyoxal-Induced Insulin Resistance by Inhibition of Advanced Glycation End Product Formation

Truong

Seo

Jun

2019

Oxidative Medicine and Cellular Longevity

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“…OxS has been recognized as especially important mechanism in IR [87]. The hormone insulin features a pivotal role in maintaining physiological levels of blood glucose through various effects on insulin target cells [88]. For instance, it elicits vasodilatory as well as vasoconstrictive effects due to the stimulation of endothelial cells for the release of endothelin and nitric oxide, thus increasing the distribution of glucose from blood to organs [89].…”

Section: Insulin Resistance Hyperglycemia and Oxidative Stressmentioning

confidence: 99%

“…Insulin is also critical for highly insulin-sensitive cells, such as muscle, hepatic, and fat ones. Transduction of insulin signal takes place via transmembrane insulin receptors (INSR), whose activation involves dimerization and autophosphorylation of tyrosines located on the intracellular part of receptors due to their kinase activity [88]. Phosphorylated tyrosines are used by adaptor proteins, such as widely known insulin receptor substrates (IRS), as docking sites.…”

Section: Insulin Resistance Hyperglycemia and Oxidative Stressmentioning

confidence: 99%

“…Phosphorylated tyrosines are used by adaptor proteins, such as widely known insulin receptor substrates (IRS), as docking sites. These molecules also undergo phosphorylation and mediate the signal via two major pathways: phosphatidyl inositol 3-kinase (PI3K) / protein kinase B (AKT), which activation results in plethora of metabolism-oriented actions, and mitogen-activated kinases (MAPK), which are mainly responsible for growth and differentiation of cells [88]. PI3K conducts phosphatidyl inositol 4,5-biphosphate (PIP2) to phosphatidyl inositol 3,4,5-triphosphate (PIP3) conversion.…”

Section: Insulin Resistance Hyperglycemia and Oxidative Stressmentioning

confidence: 99%

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The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Włodarski

Strycharz

Wróblewski

et al. 2020

IJMS

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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.

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“…Numerous studies have shown that insulin stimulates glucose uptake into peripheral tissues through activation of the insulin receptor, which phosphorylates insulin receptor substrate 1 (IRS1). This adaptor protein activates the downstream protein kinase B (AKT), which in turn induces the translocation of GLUT4, thus increasing glucose uptake and reducing the circulating glucose concentration [19,20].…”

Section: Introductionmentioning

confidence: 99%

Effect of Dietary Silk Peptide on Obesity, Hyperglycemia, and Skeletal Muscle Regeneration in High-Fat Diet-Fed Mice

Lee

Jin

Chei

et al. 2020

Cells

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Obesity is associated with excess body fat accumulation that can cause hyperglycemia and reduce skeletal muscle function and strength, which characterize the development of sarcopenic obesity. In this study, we aimed to determine the mechanism whereby acid-hydrolyzed silk peptide (SP) prevents high-fat diet (HFD)-induced obesity and whether it regulates glucose uptake and muscle differentiation using in vivo and in vitro approaches. Our findings demonstrate that SP inhibits body mass gain and the expression of adipogenic transcription factors in visceral adipose tissue (VAT). SP also had an anti-diabetic effect in VAT and skeletal muscle because it upregulated glucose transporter type 4 (GLUT4) and uncoupling protein 3 (UCP3) expression. Furthermore, SP reduced ubiquitin proteasome and promoted myoblast determination protein 1 (MyoD)/myogenic factor 4 (myogenin) expression, implying that it may have potential for the treatment of obesity-induced hyperglycemia and obesity-associated sarcopenia.

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Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

Cited by 64 publications

References 77 publications

Psoralea corylifoliaL. Seed Extract Attenuates Methylglyoxal-Induced Insulin Resistance by Inhibition of Advanced Glycation End Product Formation

Psoralea corylifoliaL. Seed Extract Attenuates Methylglyoxal-Induced Insulin Resistance by Inhibition of Advanced Glycation End Product Formation

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Effect of Dietary Silk Peptide on Obesity, Hyperglycemia, and Skeletal Muscle Regeneration in High-Fat Diet-Fed Mice

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