Insulin-regulated Glut4 Translocation

Brewer, Paul Duffield; Habtemichael, Estifanos N.; Romenskaia, Irina; Mastick, Cynthia Corley; Coster, Adelle C.F.

doi:10.1074/jbc.m114.555714

Cited by 66 publications

(62 citation statements)

References 52 publications

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“…Indeed, Rab6 and its guanine nucleotide exchange factor RICH have been shown to regulate docking of internalized recycling endosomes with the trans-Golgi network before recycling towards the plasma membrane is completed (Iwanami et al, 2016;Miserey-Lenkei et al, 2007). In mammals, internalized glucose transporter 4 (GLU4) is sorted to the Golgi before being recycled to the plasma membrane in a nutrient-dependent manner (Brewer et al, 2014). Our data support a role for Rab6 in the regulation of a similar traffic route for InR.…”

Section: Discussionsupporting

confidence: 53%

Rab6 promotes insulin receptor and cathepsin trafficking to regulate autophagy induction and activity in Drosophila

Ayala

Kim

Neufeld

2018

Journal of Cell Science

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The self-degradative process of autophagy is important for energy homeostasis and cytoplasmic renewal. This lysosome-mediated pathway is negatively regulated by the target of rapamycin kinase (TOR) under basal conditions, and requires the vesicle trafficking machinery regulated by Rab GTPases. However, the interactions between autophagy, TOR and Rab proteins remain incompletely understood Here, we identify Rab6 as a critical regulator of the balance between TOR signaling and autolysosome function. Loss of Rab6 causes an accumulation of enlarged autophagic vesicles resulting in part from a failure to deliver lysosomal hydrolases, rendering autolysosomes with a reduced degradative capacity and impaired turnover. Additionally, Rab6-deficient cells are reduced in size and display defective insulin-TOR signaling as a result of mis-sorting and internalization of the insulin receptor. Our findings suggest that Rab6 acts to maintain the reciprocal regulation between autophagy and TOR activity during distinct nutrient states, thereby balancing autophagosome production and turnover to avoid autophagic stress.

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Section: Discussionsupporting

confidence: 53%

Rab6 promotes insulin receptor and cathepsin trafficking to regulate autophagy induction and activity in Drosophila

Ayala

Kim

Neufeld

2018

Journal of Cell Science

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“…Defects in these signaling pathways are considered the major pathogenic disturbances underlying the development and progression of T2DM[ 19 ]. Decreased GLUT4 expression and cell membrane localization, increased IRS-1 phosphorylation at Ser 307 and decreased AKT phosphorylation at Ser 473 after insulin stimulation have been well documented in insulin resistance[ 20 ]. In this study, although no statistically significant difference between the noise exposed group and diet-matched control group was observed, only the HFD-N group exhibited significant decreased GLUT4 signal and AKT Ser 473 phosphorylation in skeletal muscle after 2-weeks of treatment, providing further clues at the tissue-level toward an accelerating effect of noise exposure on the diabetogenic action of the HFD.…”

Section: Discussionmentioning

confidence: 99%

Chronic noise-exposure exacerbates insulin resistance and promotes the manifestations of the type 2 diabetes in a high-fat diet mouse model

et al. 2018

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Epidemiological studies have revealed that noise exposure was associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the exact nature of that association remains to be elucidated. The present study is designed to examine the effects of chronic noise exposure on the development of T2DM in combination with a high-fat-diet (HFD) in mice. Here we show that chronic noise exposure at 85 dB SPL (4 h /day, below the safety limit for occupational noise exposure) exaggerated multiple metabolic abnormalities induced by HFD in C57BL/6J male mice, including worsened glucose intolerance, insulin resistance, fasting hyperglycemia and dyslipidemia. Furthermore, noise exposure exhibited a paradoxical impact on fat accumulation and circulating levels of free fatty acid, indicating a potential stimulating effect of noise on lipolysis. These results provide first in vivo supporting evidence for the causative role of noise exposure in diabetogenesis and pinpoint a noise-associated increase in blood free fatty acid levels as a possible mediator accelerating the effect of noise on the development of insulin resistance and T2DM.

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“…One model proposes that TBC1D4 modulates GLUT4 vesicle release from retention without altering vesicle tethering, docking or fusion with cell surface membranes [30]. Another model proposes that after releasing GLUT4 vesicles from retention secondary to TBC1D4 phosphorylation and 14-3-3 binding, the N-terminal PTB domain of TBC1D4 facilitates GLUT4 vesicle docking/fusion with the plasma membrane [31].…”

Section: Tbc1d4: Insulin-stimulated Glut4 Translocation In Adipocytesmentioning

confidence: 99%

Roles of TBC1D1 and TBC1D4 in insulin- and exercise-stimulated glucose transport of skeletal muscle

2014

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This review focuses on two paralogue Rab GTPase activating proteins known as TBC1D1 Tre-2/BUB2/cdc 1 domain family (TBC1D) 1 and TBC1D4 (also called Akt Substrate of 160 kDa, AS160) and their roles in controlling skeletal muscle glucose transport in response to the independent and combined effects of insulin and exercise. Convincing evidence implicates Akt2-dependent TBC1D4 phosphorylation on T642 as a key part of the mechanism for insulin-stimulated glucose uptake by skeletal muscle. TBC1D1 phosphorylation on several insulin-responsive sites (including T596, a site corresponding to T642 in TBC1D4) does not appear to be essential for in vivo insulin-stimulated glucose uptake by skeletal muscle. In vivo exercise or ex vivo contraction of muscle result in greater TBC1D1 phosphorylation on S237 that is likely to be secondary to increased AMP-activated protein kinase activity and potentially important for contraction-stimulated glucose uptake. Several studies that evaluated both normal and insulin-resistant skeletal muscle stimulated with a physiological insulin concentration after a single exercise session found that greater post-exercise insulin-stimulated glucose uptake was accompanied by greater TBC1D4 phosphorylation on several sites. In contrast, enhanced post-exercise insulin sensitivity was not accompanied by greater insulin-stimulated TBC1D1 phosphorylation. The mechanism for greater TBC1D4 phosphorylation in insulin-stimulated muscles after acute exercise is uncertain, and a causal link between enhanced TBC1D4 phosphorylation and increased post-exercise insulin sensitivity has yet to be established. In summary, TBC1D1 and TBC1D4 have important, but distinct roles in regulating muscle glucose transport in response to insulin and exercise.

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Insulin-regulated Glut4 Translocation

Cited by 66 publications

References 52 publications

Rab6 promotes insulin receptor and cathepsin trafficking to regulate autophagy induction and activity in Drosophila

Rab6 promotes insulin receptor and cathepsin trafficking to regulate autophagy induction and activity in Drosophila

Chronic noise-exposure exacerbates insulin resistance and promotes the manifestations of the type 2 diabetes in a high-fat diet mouse model

Roles of TBC1D1 and TBC1D4 in insulin- and exercise-stimulated glucose transport of skeletal muscle

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