Glutamine Enhances the Hypoglycemic Effect of Insulin in L6 Cells via Phosphatidylinositol-3-Kinase (PI3K)/Protein Kinase B (AKT)/Glucose Transporter 4 (GLUT4) Signaling Pathway

Wang, Caijuan; Deng, Yao; Yue, Yenan; Chen, Wenting; Zhang, Yu; Shi, Gui-Fang; Wu, Zhongming

doi:10.12659/msm.909011

Cited by 14 publications

(10 citation statements)

References 38 publications

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“…After stimulation with 100 nM of Insulin (Sigma Aldrich, St. Louis, MO), they were fixed with 4% paraformaldehyde without permeabilization and subjected to HA staining using a rabbit monoclonal anti-HA antibody (Rockland, Limerick, PA) followed by Alexa Fluor 594-conjugated goat anti-rabbit IgG (Abcam, Cambridge, UK). The Alexa Fluor 595/GFP ratio was determined by quantitative fluorescence microscopy as described previously 27 . To avoid cell selection bias fields, cells expressing the HA–Glut4-eGFP were randomly chosen in the GFP channel blinded to the expression of HA–Glut4-GFP on the plasma membrane (Alexa Fluor 594 channel).…”

Section: Methodsmentioning

confidence: 99%

DNAJB3 attenuates metabolic stress and promotes glucose uptake by eliciting Glut4 translocation

Arredouani

Diané

Khattab

et al. 2019

Sci Rep

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Failure of the heat shock response is a key event that leads to insulin resistance and type 2 diabetes. We recently showed that DNAJB3 co-chaperone is downregulated in obese and diabetic patients and that physical exercise restores its normal expression with a significant improvement of the clinical outcomes. In 3T3-L1 adipocytes, DNAJB3 has a role in improving the sensitivity to insulin and glucose uptake. In co-immunoprecipitation assays, DNAJB3 interacts with both JNK1 and IKKβ kinases. However, the functional impact of such interaction on their activities has not been investigated. Here, we assessed the effect of DNAJB3 on the respective activity of JNK1 and IKKβ in cell-based assays. Using JNK1- and IKKβ-dependent luciferase reporters, we show a marked decrease in luciferase activity by DNAJB3 in response to PMA and TNF-α that was consistent with a decrease in the translocation of p65/NF-κB to the nucleus in response to LPS. Furthermore, TNF-α-mediated IL-6 promoter activation and endogenous mRNA expression are significantly abrogated by DNAJB3 both in 3T3-L1 and C2C12 cells. The ability of DNAJB3 to mitigate ER stress and oxidative stress was also investigated and our data show a significant improvement of both forms of stress. Finally, we examined the effect of overexpressing and knocking down the expression of DNAJB3 on glucose uptake in C2C12 as well as the molecular determinants. Accordingly, we provide evidence for a role of DNAJB3 in promoting both basal and insulin-stimulated glucose uptake. Our finding reveals also a novel role of DNAJB3 in eliciting Glut4 translocation to the plasma membrane. These results suggest a physiological role of DNAJB3 in mitigating metabolic stress and improving glucose homeostasis and could therefore represent a novel therapeutic target for type 2 diabetes.

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Section: Methodsmentioning

confidence: 99%

DNAJB3 attenuates metabolic stress and promotes glucose uptake by eliciting Glut4 translocation

Arredouani

Diané

Khattab

et al. 2019

Sci Rep

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“…Herein, we will point out only a few members of this enormous group. For instance, glutamine (Gln) supplementation Gln increases the expression of key PI3K signaling molecules (PI3K, PDK1, and GLUT4) and promotes AKT phosphorylation, GLUT4 translocation, and glucose uptake in the presence of insulin during exposure to hyperglycemia [64]. An epidemic of obesity and numerous side effects of drugs that increase insulin sensitivity has caused the great interest among scientists to search for natural sensitizers.…”

Section: Insulin-sensitizing Factorsmentioning

confidence: 99%

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

Świderska¹,

Strycharz²,

Wróblewski³

et al. 2020

Blood Glucose Levels

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Glucose uptake is regulated by several mechanisms, where insulin plays the most prominent role. This powerful anabolic hormone regulates the transport of glucose into the cell through translocation of glucose transporter from an intracellular pool to the plasma membrane mainly in metabolically active tissues like skeletal muscles, adipose tissue, or liver (GLUT4). This translocation occurs through multiple steps of PI3K/AKT signaling pathway. In this chapter, we will focus on molecular events leading to GLUT4 translocation, starting with activation of insulin receptors through signaling cascade involving phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB) and finally, the action of their effectors. We will present regulatory mechanisms and modulators of insulin-mediated glucose uptake.

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“…PI3K/Akt/mTOR is a signal pathway closely related to insulin signal transduction (6,24) . The expression of PI3K and phosphorylation of Akt in kidney, liver, skeletal muscle and adipose tissue of DM rats were signi cantly decreased; in the development of DM, persistent hyperglycemia can promote the activation of PI3K / Akt signaling pathway, and ultimately accelerate the development of DM (37) . This study found that overexpression of Rab35 inhibited PI3K/Akt/mTOR signaling pathway and promoted insulin secretion; when Rab35 was inhibited, PI3K/ Akt/mTOR pathway was activated and insulin secretion was down regulated.…”

Section: Discussionmentioning

confidence: 94%

miR-720 Regulates Insulin Secretion by Targeting Rab35

Wang

Feng

et al. 2020

Preprint

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Background: miRNAs pose a good prospect in the diagnosis and treatment of type 2 diabetes (T2D). This study aimed to investigate whether miR-720 targets Rab35 to regulate insulin secretion in MIN6 cells and its molecular mechanism, and the clinical value of miR-720 as a specific biomarker of T2D. Methods: Fifty-five samples of new diagnosis T2D patients and normal control were collected. Levels of miR-720, fasting blood glucose, insulin and other indicators of glucose and lipid metabolism were determined. We increased and decreased miR-720 expression using miR-720 mimic and inhibitor to identify the effect of miR-720 on insulin secretion in MIN6 cells, respectively. Then we used miR-720 mimic, miR-720 inhibitor and dual luciferase reporter gene assays to prove miR-720 regulate insulin secretion by targeting Rab35 in MIN6 cells. In addition, we overexpressed and silenced of Rab35 gene to detect the expression of PI3K, Akt and mTOR in MIN6 cells by RT-PCR and western blot. Results: Circulating miR-720 was significantly higher in T2D group than control group, and miR-270 was positive correlated with fasting blood glucose, while negatively correlated with insulin. Overexpression of miR-720 inhibited insulin secretion and miR-720 downregulation promoted insulin secretion. miR-720 regulated insulin secretion by targeting Rab35 in MIN6 cells. Compared with the control group, the expression of PI3K, Akt and mTOR was significantly decreased by overexpression of Rab35 gene, while silencing Rab35 gene could induce the expression of PI3K, Akt and mTOR. Conclusions: We conclude that miR-720 may as a potential biomarker for the diagnosis of T2D. Increase of miR-720 reduced Rab35 expression then activate PI3K/Akt/mTOR signal pathway, thus inhibiting insulin secretion.

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Glutamine Enhances the Hypoglycemic Effect of Insulin in L6 Cells via Phosphatidylinositol-3-Kinase (PI3K)/Protein Kinase B (AKT)/Glucose Transporter 4 (GLUT4) Signaling Pathway

Cited by 14 publications

References 38 publications

DNAJB3 attenuates metabolic stress and promotes glucose uptake by eliciting Glut4 translocation

DNAJB3 attenuates metabolic stress and promotes glucose uptake by eliciting Glut4 translocation

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

miR-720 Regulates Insulin Secretion by Targeting Rab35

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