Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells

Zhao, Ping; Tian, Di; Song, Guanjun; Ming, Qian; Liu, Jia; Shen, Jinhua; Liu, Qinghua; Yang, Xinzhou

doi:10.3389/fphar.2019.00999

Cited by 32 publications

(25 citation statements)

References 48 publications

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“…IRS1 and PI3 K mRNA levels were also increased by the action of insulin and bark extract. The same conclusion was reached by Zhao et al (2019) who reported an increase mRNA expression level of GLUT-4, following a treatment of L6 with neferine, an alkaloid derived from lotus seeds and insulin. 46 There was an upregulation of Akt1, Akt2 and peroxisome proliferator-activated receptor g (PPAR-g) in C2C12 cells treated with leaf and seed extracts (Figure 4).…”

Section: Gene Expression Of Irs1 Pi3 K Akt1 Akt2 Ppar-g and Glut-4supporting

confidence: 70%

Cassia Abbreviata Enhances Glucose Uptake and Glucose Transporter 4 Translocation in C2C12 Mouse Skeletal Muscle Cells

Kamga-Simo

Kamatou

Ssemakalu

et al. 2021

J Evid Based Complementary Altern Med

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Background. This study aim at assessing C. abbreviata aqueous extracts for its potential to exhibit anti-diabetic activity in skeletal muscle cells. In addition to the toxicological and glucose absorption studies, the action of C. abbreviata extracts on some major genes involved in the insulin signaling pathway was established. Methods. The in vitro cytotoxic effects C. abbreviata was evaluated on muscle cells using the MTT assay and the in vitro glucose uptake assay conducted using a modified glucose oxidase method described by Van de Venter et al. (2008). The amount of GLUT-4 on cell surfaces was estimated quantitatively using the flow cytometry technique. Real time quantitative PCR (RT-qPCR) was used to determine the expression of GLUT-4, IRS-1, PI3 K, Akt1, Akt2, PPAR-γ. Results. Cytotoxicity tests revealed that all extracts tested at various concentrations were non-toxic (LC50 > 5000). Aqueous extracts of leaves, bark and seeds resulted in a dose-dependent increase in glucose absorption by cells, after 1 h, 3 h and 6 h incubation period. Extracts of all three plant parts had the best effect after 3 h incubation, with the leaf extract showing the best activity across time (Glucose uptake of 29%, 56% and 42% higher than untreated control cells after treatment with 1 mg/ml extract at 1 h, 3 h and 6 h, respectively). All extracts, with the exception 500 µg/ml seed extract, induced a two-fold increase in GLUT-4 translocation while marginally inducing GLUT-10 translocation in the muscle cells. The indirect immunofluorescence confirmed that GLUT-4 translocation indeed occurred. There was an increased expression of GLUT-4, IRS1 and PI3 K in cells treated with insulin and bark extract as determined by the RT-qPCR. Conclusion. The study reveals that glucose uptake involves GLUT-4 translocation through a mechanism that is likely to involve the upstream effectors of the PI3-K/Akt pathway.

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Section: Gene Expression Of Irs1 Pi3 K Akt1 Akt2 Ppar-g and Glut-4supporting

confidence: 70%

Cassia Abbreviata Enhances Glucose Uptake and Glucose Transporter 4 Translocation in C2C12 Mouse Skeletal Muscle Cells

Kamga-Simo

Kamatou

Ssemakalu

et al. 2021

J Evid Based Complementary Altern Med

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“…Second, Ca 2+ signaling affects glucose utilization by regulating the insulin signaling pathway. The G protein/IP3/IP3R pathway is involved in glucose transporter 4 (GLUT4)-plasma membrane fusion, while pharmaceutically induced GLUT4-plasma membrane fusion and glucose uptake are inhibited by treatment with a Ca 2+ chelator, suggesting that these processes are Ca 2+dependent (35).…”

Section: Calcium Homeostasismentioning

confidence: 99%

The Molecular Mechanisms Underlying Mitochondria-Associated Endoplasmic Reticulum Membrane-Induced Insulin Resistance

Cheng

Gang

et al. 2020

Front. Endocrinol.

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Mitochondria and the endoplasmic reticulum (ER) are connected at multiple sites via what are known as mitochondria-associated ER membranes (MAMs). These associations are known to play an important role in maintaining cellular homeostasis. Impaired MAM signaling has wide-ranging effects in many diseases, such as obesity, diabetes, and neurodegenerative disorders. Accumulating evidence has suggested that MAMs influence insulin signaling through different pathways, including those associated with Ca2+ signaling, lipid metabolism, mitochondrial function, ER stress responses, and inflammation. Altered MAM signaling is a common feature of insulin resistance in different tissues, including the liver, muscle, and even the brain. In the liver, MAMs are key glucose-sensing regulators and have been proposed to be a hub for insulin signaling. Impaired MAM integrity has been reported to disrupt hepatic responses to changes in glucose availability during nutritional transition and to induce hepatic insulin resistance. Meanwhile, these effects can be rescued by the reinforcement of MAM interactions. In contrast, several studies have proposed that enhanced ER-mitochondria connections are detrimental to hepatic insulin signaling and can lead to mitochondrial dysfunction. Thus, given these contradictory results, the role played by the MAM in the regulation of hepatic insulin signaling remains elusive. Similarly, in skeletal muscle, enhanced MAM formation may be beneficial in the early stage of diabetes, whereas continuous MAM enhancement aggravates insulin resistance. Furthermore, recent studies have suggested that ER stress may be the primary pathway through which MAMs induce brain insulin resistance, especially in the hypothalamus. This review will discuss the possible mechanisms underlying MAM-associated insulin resistance as well as the therapeutic potential of targeting the MAM in the treatment of type 2 diabetes.

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“…GLUT4 is an insulin-responsive glucose transporter that mediates glucose influx in the muscle cells. It has been reported that GLUT4 expression and translocation could be regulated through the G-protein-phospholipase C-protein kinase C and 5' adenosine monophosphate (AMP)-activated protein kinase pathway in muscle cells (37). Impaired expression of GLUT4 has been reported to be linked to obesity, type 1 diabetes, and type 2 diabetes (38).…”

Section: Discussionmentioning

confidence: 99%

Red rice koji extract alleviates hyperglycemia by increasing glucose uptake and glucose transporter type 4 levels in skeletal muscle in two diabetic mouse models

Yagi

Ataka

Cheng

et al. 2020

Food & Nutrition Research

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Background: Red rice koji (RRK), prepared by growing Monascus species on steamed rice, has been reported to lower blood glucose levels in diabetic animal models. However, the action mechanism is not yet completely understood. Objective: The objective of this study was to examine the mechanism underlying the hypoglycemic action of RRK extract in two diabetic animal models: the insulin-deficiency mice, where the insulin deficiency was induced by streptozotocin (STZ), and insulin-resistance mice, where the insulin resistance was induced by a high-fat diet (HFD). Design: Low (12.5 mg/kg body weight [BW]) and high (50.0 mg/kg BW) doses of RRK extract were orally administered to the mice for 10 successive days (0.25 mL/day/mouse). The protein expression levels of glucose transporter type 4 (GLUT4) in the skeletal muscle and glucose transporter type 2 (GLUT2) in the liver were measured. Blood glucose (BG) levels of STZ-treated mice in insulin tolerance test (ITT) and BG and insulin levels of HFD-fed mice in intraperitoneal glucose tolerance test (IPGTT) were investigated. Results: In the STZ-treated mice, oral administration of RRK extract lowered BG levels and food intake but increased plasma 1,5-anhydroglucitol level. Moreover, the RRK extract lowered the BG levels of STZ-treated mice as measured by ITT. In the HFD-fed mice, we confirmed that the orally administered RRK extract lowered the BG and the homeostasis model assessment index for insulin resistance. Furthermore, the RRK extract lowered the BG and insulin levels of HFD-fed mice in IPGTT. Regarding the protein levels of GLUT, the orally administered RRK extract increased the GLUT4 level in the skeletal muscle; however, the RRK extract did not alter the GLUT2 level in the liver of either the STZ-treated or the HFD-fed mice. Popular scientific summary • Red rice koji (RRK) extract lowered blood glucose levels in streptozotocin (STZ)-treated and highfat diet (HFD)-fed mice and food intake in STZ-treated mice. • RRK extract lowered blood glucose levels of STZ-treated mice in insulin tolerance test and blood glucose and insulin levels of HFD-fed mice in intraperitoneal glucose tolerance test. • RRK extract increased glucose transporter type 4 level in the skeletal muscle of both STZ-treated and HFD-fed mice.

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Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells

Cited by 32 publications

References 48 publications

Cassia Abbreviata Enhances Glucose Uptake and Glucose Transporter 4 Translocation in C2C12 Mouse Skeletal Muscle Cells

Cassia Abbreviata Enhances Glucose Uptake and Glucose Transporter 4 Translocation in C2C12 Mouse Skeletal Muscle Cells

The Molecular Mechanisms Underlying Mitochondria-Associated Endoplasmic Reticulum Membrane-Induced Insulin Resistance

Red rice koji extract alleviates hyperglycemia by increasing glucose uptake and glucose transporter type 4 levels in skeletal muscle in two diabetic mouse models

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