scholarly journals Galangin and Pinocembrin from Propolis Ameliorate Insulin Resistance in HepG2 Cells via Regulating Akt/mTOR Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yinkang Liu ◽  
Xiali Liang ◽  
Gensheng Zhang ◽  
Lingjie Kong ◽  
Wenjun Peng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Pyruvate Kinase ◽  
Glycogen Content ◽  
Critical Role ◽  
Glucose Consumption ◽  
Mtor Signaling ◽  
Compelling Evidence ◽  
Mtor Signaling Pathway ◽  
Ameliorate Insulin Resistance

Insulin resistance has a critical role in type 2 diabetes. The aim of this study was to investigate the effect of pinobanksin, galangin, chrysin, and pinocembrin from propolis on insulin resistance. Our study shows that galangin and pinocembrin can ameliorate insulin resistance; on the contrary, pinobanksin and chrysin are ineffective. Galangin and pinocembrin treatments substantially increase glucose consumption and glycogen content by enhancing the activities of hexokinase and pyruvate kinase. Galangin treatment with 80 μM increased hexokinase and pyruvate kinase activities by 21.94% and 29.12%, respectively. Moreover, we hypothesize that galangin and pinocembrin may have a synergistic effect on the improvement of insulin resistance via Akt/mTOR signaling pathway, through distinctly upregulating the phosphorylation of IR, Akt, and GSK3β and remarkably downregulating the phosphorylation of IRS. Most notably, this is the first study to our knowledge to investigate pinocembrin about the alleviation of insulin resistance. Our results provide compelling evidence for the depth development of propolis products to ameliorate insulin resistance.

Targeting mTOR Signaling in Type 2 Diabetes Mellitus and Diabetes Complications

2022 ◽  
Vol 23 ◽  
Author(s):  
Lin Yang ◽  
Zhixin Zhang ◽  
Doudou Wang ◽  
Yu Jiang ◽  
Ying Liu
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Protein Complexes ◽  
Cell Metabolism ◽  
Critical Role ◽  
Mtor Inhibitors ◽  
Mtor Signaling

Abstract: The mechanistic target of rapamycin (mTOR) is a pivotal regulator of cell metabolism and growth. In the form of two different multi-protein complexes, mTORC1 and mTORC2, mTOR integrates cellular energy, nutrient and hormonal signals to regulate cellular metabolic homeostasis. In type 2 diabetes mellitus (T2DM) aberrant mTOR signaling underlies its pathological conditions and end-organ complications. Substantial evidence suggests that two mTOR-mediated signaling schemes, mTORC1-p70S6 kinase 1 (S6K1) and mTORC2-protein kinase B (AKT), play a critical role in insulin sensitivity and that their dysfunction contributes to development of T2DM. This review summaries our current understanding of the role of mTOR signaling in T2DM and its associated complications, as well as the potential use of mTOR inhibitors in treatment of T2DM.

scholarly journals Role of T Lymphocytes in Type 2 Diabetes and Diabetes-Associated Inflammation

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Chang Xia ◽  
Xiaoquan Rao ◽  
Jixin Zhong
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
T Cells ◽  
Immune System ◽  
Critical Role ◽  
Adaptive Immune System ◽  
Metabolic Inflammation ◽  
Adaptive Immune

Although a critical role of adaptive immune system has been confirmed in driving local and systemic inflammation in type 2 diabetes and promoting insulin resistance, the underlying mechanism is not completely understood. Inflammatory regulation has been focused on innate immunity especially macrophage for a long time, while increasing evidence suggests T cells are crucial for the development of metabolic inflammation and insulin resistance since 2009. There was growing evidence supporting the critical implication of T cells in the pathogenesis of type 2 diabetes. We will discuss the available effect of T cells subsets in adaptive immune system associated with the procession of T2DM, which may unveil several potential strategies that could provide successful therapies in the future.

scholarly journals The mTOR Signaling Pathway in Myocardial Dysfunction in Type 2 Diabetes Mellitus

2017 ◽  
Vol 17 (6) ◽  
Author(s):  
Tomohiro Suhara ◽  
Yuichi Baba ◽  
Briana K. Shimada ◽  
Jason K. Higa ◽  
Takashi Matsui
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Myocardial Dysfunction ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway

scholarly journals GPR30 Activation by 17β-Estradiol Promotes p62 Phosphorylation and Increases Estrogen Receptor α Protein Expression by Inducing Its Release from a Complex Formed with KEAP1

2021 ◽  
Vol 11 (9) ◽  
pp. 906
Author(s):  
Chia-Lung Tsai ◽  
Chiao-Yun Lin ◽  
Angel Chao ◽  
Yun-Shien Lee ◽  
Ren-Chin Wu ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Critical Role ◽  
Adaptor Protein ◽  
Estrogen Receptor Α ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
17Β Estradiol ◽  
Esr1 Expression

Estrogens can elicit rapid cellular responses via the G-protein-coupled receptor 30 (GPR30), followed by estrogen receptor α (ERα/ESR1)-mediated genomic effects. Here, we investigated whether rapid estrogen signaling via GRP30 may affect ESR1 expression, and we examined the underlying molecular mechanisms. The exposure of human endometrial cancer cells to 17β-estradiol promoted p62 phosphorylation and increased ESR1 protein expression. However, both a GPR30 antagonist and GPR30 silencing abrogated this phenomenon. GPR30 activation by 17β-estradiol elicited the SRC/EGFR/PI3K/Akt/mTOR signaling pathway. Intriguingly, unphosphorylated p62 and ESR1 were found to form an intracellular complex with the substrate adaptor protein KEAP1. Upon phosphorylation, p62 promoted ESR1 release from the complex, to increase its protein expression. Given the critical role played by p62 in autophagy, we also examined how this process affected ESR1 expression. The activation of autophagy by everolimus decreased ESR1 by promoting p62 degradation, whereas autophagy inhibition with chloroquine increased ESR1 expression. The treatment of female C57BL/6 mice with the autophagy inhibitor hydroxychloroquine—which promotes p62 expression—increased both phosphorylated p62 and ESR1 expression in uterine epithelial cells. Collectively, our results indicate that 17β-estradiol-mediated GPR30 activation elicits the SRC/EGFR/PI3K/Akt/mTOR signaling pathway and promotes p62 phosphorylation. In turn, phosphorylated p62 increased ESR1 expression by inducing its release from complexes that included KEAP1. Our findings may lead to novel pharmacological strategies aimed at decreasing ESR1 expression in estrogen-sensitive cells.

scholarly journals Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

2020 ◽  
Author(s):  
Guang Chen ◽  
Xiao-yan Fan ◽  
Xiao-peng Zheng ◽  
Yue-lei Jin ◽  
Ying Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Type 2 Diabetes Mellitus ◽  
Human Umbilical Cord ◽  
Tail Vein Injection ◽  
Ameliorate Insulin Resistance

Abstract Background: Globally, 1 in 11 adults have diabetes mellitus and 90% of the cases are type 2 diabetes mellitus. Asia is the epicenter of this global type 2 diabetes mellitus epidemic. Type 2 diabetes mellitus and its complications have contributed significantly to the burden of mortality and disability worldwide. Insulin resistance is a central defect in type 2 diabetes mellitus, and although multiple drugs have been developed to ameliorate insulin resistance, the limitations and accompanying side effects cannot be ignored. Thus more effective methods are required to improve insulin resistance. Methods: In the current study, db/m and db/db mice were injected with human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) via tail vein injection, intraperitoneal injection and skeletal muscle injection. Body weight, fasting blood glucose and the survival rates were monitored. Furthermore, the anti-insulin resistance effects and potential mechanisms of transplanted HUC-MSCs were investigated in db/db mice in vivo. Results: The results showed that HUC-MSC transplantation by skeletal muscle injection was safer compared with tail vein injection and intraperitoneal injection, and the survival rate reached 100% in the skeletal muscle injection transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate insulin resistance. Potential regulatory mechanisms are associated with downregulation of inflammation; regulating the balance between PI3K/Akt and ERK/MAPK signaling pathway via PTEN, but was not associated with the IGF-1/IGF-1R signaling pathway. Conclusions: These results suggest HUC-MSC transplantation may be a novel therapeutic direction to prevent insulin resistance and increase insulin sensitivity, and skeletal muscle injection was the safest and most effective way.

scholarly journals Serum from Jiao-Tai-Wan treated rats increases glucose consumption by 3T3-L1 adipocytes through AMPK pathway signaling

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Lin Yuan ◽  
Peng Tang ◽  
Hui-Jiao Li ◽  
Na Hu ◽  
Xiao-Yu Zhong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Transporter ◽  
Glucose Consumption ◽  
Diabetic Mouse ◽  
Rat Serum ◽  
Insulin Resistant ◽  
Ampk Pathway ◽  
Compound C ◽  
Type 2 Diabetic

Abstract Type 2 diabetes (T2DM) is characterized by hyperglycemia resulting from insulin resistance. Jiao-Tai-Wan (JTW), a traditional Chinese medicine consisting of a 10:1 formulation of Rhizoma Coptidis (RC) and Cortex Cinnamomi (cinnamon) was shown to have hypoglycemic efficacy in a type 2 diabetic mouse model. Here we investigated whether glucose consumption by insulin-resistant adipocytes could be modulated by serum from JTW-treated rats, and if so, through what mechanism. JTW-medicated serum was prepared from rats following oral administration of JTW decoction twice a day for 4 days. Fully differentiated 3T3-L1 adipocytes – rendered insulin resistance by dexamethasone treatment – were cultured in medium containing JTW-medicated rat serum. JTW-medicated serum treatment increased glucose uptake, up-regulated levels of phosphorylated adenosine 5′-monophoshate-activated protein kinase (p-AMPK), and stimulated expression and translocation of glucose transporter 4 (GLUT4). JTW-medicated serum induced significantly greater up-regulation of p-AMPK and GLUT4 than either RC or cinnamon-medicated serum. JTW-medicated serum induced effects on 3T3-L1 adipocytes could be partially inhibited by treatment with the AMPK inhibitor compound C. In conclusion, JTW-medicated serum increased glucose consumption by IR adipocytes partially through the activation of the AMPK pathway, and JTW was more effective on glucose consumption than either RC or cinnamon alone.

scholarly journals Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Guang Chen ◽  
Xiao-yan Fan ◽  
Xiao-peng Zheng ◽  
Yue-lei Jin ◽  
Ying Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Type 2 Diabetes Mellitus ◽  
Human Umbilical Cord ◽  
Tail Vein Injection ◽  
Ameliorate Insulin Resistance

Abstract Background Globally, 1 in 11 adults have diabetes mellitus, and 90% of the cases are type 2 diabetes mellitus. Insulin resistance is a central defect in type 2 diabetes mellitus, and although multiple drugs have been developed to ameliorate insulin resistance, the limitations and accompanying side effects cannot be ignored. Thus, more effective methods are required to improve insulin resistance. Methods In the current study, db/m and db/db mice were injected with human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) via tail vein injection, intraperitoneal injection, and skeletal muscle injection. Body weight, fasting blood glucose, and the survival rates were monitored. Furthermore, the anti-insulin resistance effects and potential mechanisms of transplanted HUC-MSCs were investigated in db/db mice in vivo. Results The results showed that HUC-MSC transplantation by skeletal muscle injection was safer compared with tail vein injection and intraperitoneal injection, and the survival rate reached 100% in the skeletal muscle injection transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate insulin resistance. Potential regulatory mechanisms are associated with downregulation of inflammation, regulating the balance between PI3K/Akt and ERK/MAPK signaling pathway via PTEN, but was not associated with the IGF-1/IGF-1R signaling pathway. Conclusions These results suggest HUC-MSC transplantation may be a novel therapeutic direction to prevent insulin resistance and increase insulin sensitivity, and skeletal muscle injection was the safest and most effective way.

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