Cooperative actions of Tbc1d1 and AS160/Tbc1d4 in GLUT4-trafficking activities

Hatakeyama, Hiroyasu; Morino, Taisuke; Ishii, Takuya; Kanzaki, Makoto

doi:10.1074/jbc.ra118.004614

Cited by 23 publications

(23 citation statements)

References 36 publications

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“…Besides, a study indicates that PI3K/AKT pathway works as upstream signaling to stimulate the GLUT4 translocation to the cell surface in cardiomyocytes, thereby promoting glucose uptake (Yuan Y et al, 2019). During this procedure, GLUT4 translocation is mediated by AS160, which is activated through AKT phosphorylation (Hatakeyama H et al, 2019). Based on these discoveries, we propose that PI3K/AKT/AS160/GLUT4 signaling pathway plays an important role in the glucose uptake process during diabetes mellitus and its complications, like DN.…”

Section: Discussionmentioning

confidence: 92%

Berberine Interferes With the Abnormal Glomerular Mesangial Cell C Ycle Re-Distribution to Alleviate Diabetic Nephropathy via PI3K/AKT/AS160/GLUT4 Signaling Pathway

Guan

Zeng

et al. 2021

Preprint

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Background: Berberine plays a critical role of the glomerular mesangial cells (GMCs) abnormal proliferation during diabetic nephropathy (DN). This study aims to explore the intervention effect of BBR on DN mice and investigate the potential mechanism targeting abnormal GMCs proliferation. Methods: Streptozotocin-induced mice were used to determine the effect of BBR on the renal injury. In vitro, GMCs are cultured in high glucose (30 mmol/L). EdU and MTT assay are used for screening the optimum BBR concentration and intervention time. Flow cytometry is applied to analyze the cell cycle re-distribution. Western blot and RT-qPCR are devoted to studying the relative expression of molecules in PI3K/AKT/AS160/GLUT4 signaling pathway. Additionally, 2-NBDG assay is selected for measuring the glucose uptake of GMCs. Results: HE and PAS staining revealed that the notable mesangial matrix expansion, glomerular hypertrophy and glycogen deposition in diabetic kidney can be alleviated after BBR treatment. Moreover, BBR significantly reduced the positive expression of GLUT4 in tubulointerstitium and glomerular region. EdU shows that high glucose induces the abnormal proliferation of GMCs, which becomes more apparently as time goes on (20h→28h). Meantime, BBR (60 and 90 μmol/L) can not only increase the proportion of G1 phase, but also reduce the proportion of S phase. After 24 h, the same sort of phenomenon has cropped up in BBR (30 μmol/L) group. BBR (60 μmol/L)) significantly degraded the levels of PI3K-p85, p-AKT, p-AS160, and the membrane-GLUT4, while indistinguishable changes of their total protein expressions. Additionally, BBR prominently reduced the glucose uptake and retard the cell cycle of GMCs to stay at G1 phase. Conclusions: The rearrangement effect of BBR on cell cycle is related with PI3K/AKT signaling pathway and GLUT4 trafficking. The key findings of our study collectively indicate that the treatment of GMCs proliferation can be a novel therapeutic strategy in DN.

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Section: Discussionmentioning

confidence: 92%

Berberine Interferes With the Abnormal Glomerular Mesangial Cell C Ycle Re-Distribution to Alleviate Diabetic Nephropathy via PI3K/AKT/AS160/GLUT4 Signaling Pathway

Guan

Zeng

et al. 2021

Preprint

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“…These two insulin-dependent pathways (PI3K-Akt-AS160-Rab and Cbl-CAP-CrkII-C3G-TC10 pathways) induce an GDP-GTP switch and activate small G proteins, an important step in the trafficking of GLUT4 storage vesicles (GSV) to the PM [ 94 ]. Transport of GSV into the close vicinity with the PM is followed by the docking and fusion of the vesicles, with the support of SNARE complexes of proteins [ 93 , 95 ].…”

Section: Glut4 Translocationmentioning

confidence: 99%

Activation of Insulin Signaling by Botanical Products

Rosenzweig

Sampson

2021

IJMS

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Type 2 diabetes (T2D) is a worldwide health problem, ranked as one of the leading causes for severe morbidity and premature mortality in modern society. Management of blood glucose is of major importance in order to limit the severe outcomes of the disease. However, despite the impressive success in the development of new antidiabetic drugs, almost no progress has been achieved with regard to the development of novel insulin-sensitizing agents. As insulin resistance is the most eminent factor in the patho-etiology of T2D, it is not surprising that an alarming number of patients still fail to meet glycemic goals. Owing to its wealth of chemical structures, the plant kingdom is considered as an inventory of compounds exerting various bioactivities, which might be used as a basis for the development of novel medications for various pathologies. Antidiabetic activity is found in over 400 plant species, and is attributable to varying mechanisms of action. Nevertheless, relatively limited evidence exists regarding phytochemicals directly activating insulin signaling, which is the focus of this review. Here, we will list plants and phytochemicals that have been found to improve insulin sensitivity by activation of the insulin signaling cascade, and will describe the active constituents and their mechanism of action.

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“…Previously, we demonstrated that, in L6 myotubes, TBC1D4 deficiency increased the expression of CD36/SR-B2 and FABPpm, which, in turn, enhanced fatty acid influx into the muscle cells [ 13 ]. Importantly, AS160 (TBC1D4) has a less known structural homolog, TBC1D1, which has also been implicated in GLUT4 incorporation into the plasma membrane [ 16 ]. Given the above, we decided to add two additional experimental groups to our study, namely, the cells with the knocked down TBC1D1 and those with the simultaneous knockdown of both TBC1D1 and TBC1D4 .…”

Section: Introductionmentioning

confidence: 99%

Does TBC1D4 (AS160) or TBC1D1 Deficiency Affect the Expression of Fatty Acid Handling Proteins in the Adipocytes Differentiated from Human Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Obtained from Subcutaneous and Visceral Fat Depots?

Mikłosz

Łukaszuk

Supruniuk

et al. 2021

Cells

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TBC1D4 (AS160) and TBC1D1 are Rab GTPase-activating proteins that play a key role in the regulation of glucose and possibly the transport of long chain fatty acids (LCFAs) into muscle and fat cells. Knockdown (KD) of TBC1D4 increased CD36/SR-B2 and FABPpm protein expressions in L6 myotubes, whereas in murine cardiomyocytes, TBC1D4 deficiency led to a redistribution of CD36/SR-B2 to the sarcolemma. In our study, we investigated the previously unexplored role of both Rab-GAPs in LCFAs uptake in human adipocytes differentiated from the ADMSCs of subcutaneous and visceral adipose tissue origin. To this end we performed a single- and double-knockdown of the proteins (TBC1D1 and TBC1D4). Herein, we provide evidence that AS160 mediates fatty acid entry into the adipocytes derived from ADMSCs. TBC1D4 KD resulted in quite a few alterations to the cellular phenotype, the most obvious of which was the shift of the CD36/SR-B2 transport protein to the plasma membrane. The above translated into an increased uptake of saturated long-chain fatty acid. Interestingly, we observed a tissue-specific pattern, with more pronounced changes present in the adipocytes derived from subADMSCs. Altogether, our data show that in human adipocytes, TBC1D4, but not TBC1D1, deficiency increases LCFAs transport via CD36/SR-B2 translocation.

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Cooperative actions of Tbc1d1 and AS160/Tbc1d4 in GLUT4-trafficking activities

Cited by 23 publications

References 36 publications

Berberine Interferes With the Abnormal Glomerular Mesangial Cell C Ycle Re-Distribution to Alleviate Diabetic Nephropathy via PI3K/AKT/AS160/GLUT4 Signaling Pathway

Berberine Interferes With the Abnormal Glomerular Mesangial Cell C Ycle Re-Distribution to Alleviate Diabetic Nephropathy via PI3K/AKT/AS160/GLUT4 Signaling Pathway

Activation of Insulin Signaling by Botanical Products

Does TBC1D4 (AS160) or TBC1D1 Deficiency Affect the Expression of Fatty Acid Handling Proteins in the Adipocytes Differentiated from Human Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Obtained from Subcutaneous and Visceral Fat Depots?

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