Prior exercise in humans redistributes intramuscular GLUT4 and enhances insulin-stimulated sarcolemmal and endosomal GLUT4 translocation

Knudsen, Jonas R.; Steenberg, Dorte E.; Hingst, Janne R.; Hodgson, Lorna; Henríquez‐Olguín, Carlos; Li, Zhencheng; Kiens, Bente; Verkade, Paul; Jensen, Thomas E.

doi:10.1016/j.molmet.2020.100998

Cited by 33 publications

(34 citation statements)

References 55 publications

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“…Exercise increases the migration of glucose transporter 4 (GLUT4) to the t‐tubuli, whereas the concentration at the sarcolemma is unaffected (Knudsen et al . 2020), which together with increased glucose concentration in the t‐tubuli allows high glucose uptake over the tubular membrane. With hexokinase bound to GLUT4 (Zaid et al .…”

Section: Discussionmentioning

confidence: 99%

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Heterogeneity in subcellular muscle glycogen utilisation during exercise impacts endurance capacity in men

Jensen

Ørtenblad

Stausholm

et al. 2020

The Journal of Physiology

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When muscle biopsies first began to be used routinely in research on exercise physiology five decades ago, it soon become clear that the muscle content of glycogen is an important determinant of exercise performance. r Glycogen particles are stored in distinct pools within the muscles, but the role of each pool during exercise and how this is affected by diet is unknown. r Here, the effects of diet and exercise on these pools, as well as their relation to endurance during prolonged cycling were examined. r We demonstrate here that an improved endurance capacity with high carbohydrate loading is associated with a temporal shift in the utilisation of the distinct stores of glycogen pools and is closely linked to the content of the glycogen pool closest to actin and myosin (intramyofibrillar glycogen). r These findings highlight the functional importance of distinguishing between different subcellular microcompartments of glycogen in individual muscle fibres.

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Section: Discussionmentioning

confidence: 99%

“…In this context, the recently reported translocation of GLUT4 to the t‐tubular membrane induced by exercise is intriguing (Knudsen et al . 2020).…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity in subcellular muscle glycogen utilisation during exercise impacts endurance capacity in men

Jensen

Ørtenblad

Stausholm

et al. 2020

The Journal of Physiology

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“…According to a number of studies, GLUT4 is the only transporter responsible for facilitating glucose transport into cells in response to insulin (Thorens B et al, 2010), and is considered as a vital regulator of entire body glucose homeostasis (Chung JJ et al, 2020;Knudsen JR et al, 2020). Meantime, studies suggest that the recruitment of GLUT4 to the membrane is essential for the glucose uptake process (Thorens B et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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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“…The regulatory mechanisms by which prior exercise enhances muscle insulin action are not fully elucidated. In muscle of rats and humans, increased insulin-stimulated abundance of glucose transporter 4 (GLUT4) at the plasma membrane as well as increased membrane permeability to glucose have been shown after a single bout of exercise (Hansen et al 1998;McConell et al 2020;Knudsen et al 2020). Exercise has also been shown to potentiate insulin-induced muscle microvascular perfusion (Sjøberg et al 2017).…”

Section: Introductionmentioning

confidence: 99%

The insulin‐sensitizing effect of a single exercise bout is similar in type I and type II human muscle fibres

Larsen

Steenberg

Birk

et al. 2020

The Journal of Physiology

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Key points Rodent studies suggest muscle fibre type‐specific insulin response in the recovery from exercise. The current study investigates muscle fibre type‐specific insulin action in the recovery from exercise in healthy subjects. In type I and type II muscle fibres, key proteins in glucose metabolism are similarly regulated by insulin during recovery from exercise. Our findings imply that both type I and type II muscle fibres contribute to the phenomenon of increased insulin sensitivity in the recovery from a single bout of exercise in humans. Abstract Human skeletal muscle consists of slow‐twitch (type I) and fast‐twitch (type II) muscle fibres. Muscle insulin action, regulating glucose uptake and metabolism, is improved following a single exercise bout. Rodent studies suggest that this phenomenon is confined to specific muscle fibre types. Whether this phenomenon is also confined to specific fibre types in humans has not been described. To investigate this, nine healthy men underwent a euglycaemic hyperinsulinaemic clamp (EHC) in the recovery from a single bout of one‐legged knee‐extensor exercise. Pools of type I and type II fibres were prepared from muscle biopsies taken in the rested and prior exercised leg before and after the EHC. AMPK γ3 and TBC1D4 – two key proteins regulating muscle insulin action following exercise – were higher expressed in type II than type I fibres. However, phosphor‐regulation of TBC1D4 was similar between fibre types when related to the total amount of TBC1D4 protein. The activating dephosphorylation of glycogen synthase was also similar in the two fibre types. Thus, insulin‐induced regulation of key proteins important for transport and intracellular flux of glucose towards glycogen storage in the recovery from exercise, does not differ between fibre types. In conclusion, the insulin‐sensitizing effect of a single bout of exercise includes both type I and type II fibres in human skeletal muscle. This may be an important observation for future pharmacological strategies targeting muscle insulin sensitivity in humans.

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Prior exercise in humans redistributes intramuscular GLUT4 and enhances insulin-stimulated sarcolemmal and endosomal GLUT4 translocation

Cited by 33 publications

References 55 publications

Heterogeneity in subcellular muscle glycogen utilisation during exercise impacts endurance capacity in men

Heterogeneity in subcellular muscle glycogen utilisation during exercise impacts endurance capacity in men

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

The insulin‐sensitizing effect of a single exercise bout is similar in type I and type II human muscle fibres

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