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The exocyst complex regulates insulin-stimulated glucose uptake of skeletal muscle cells.

American journal of physiology. Endocrinology and metabolism | 2019

Skeletal muscle handles ~80-90% of the insulin-induced glucose uptake. In skeletal muscle, insulin binding to its cell surface receptor triggers redistribution of intracellular glucose transporter GLUT4 protein to the cell surface, enabling facilitated glucose uptake. In adipocytes, the eight-protein exocyst complex is an indispensable constituent in insulin-induced glucose uptake, as it is responsible for the targeted trafficking and plasma membrane-delivery of GLUT4. However, the role of the exocyst in skeletal muscle glucose uptake has never been investigated. Here we demonstrate that the exocyst is a necessary factor in insulin-induced glucose uptake in skeletal muscle cells as well. The exocyst complex colocalizes with GLUT4 storage vesicles in L6-GLUT4myc myoblasts at a basal state and associates with these vesicles during their translocation to the plasma membrane after insulin signaling. Moreover, we show that the exocyst inhibitor endosidin-2 and a heterozygous knockout of Exoc5 in skeletal myoblast cells both lead to impaired GLUT4 trafficking to the plasma membrane and hinder glucose uptake in response to an insulin stimulus. Our research is the first to establish that the exocyst complex regulates insulin-induced GLUT4 exocytosis and glucose metabolism in muscle cells. A deeper knowledge of the role of the exocyst complex in skeletal muscle tissue may help our understanding of insulin resistance in type 2 diabetes.

Pubmed ID: 31593505 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

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Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK117308
  • Agency: NHLBI NIH HHS, United States
    Id: K01 HL140271
  • Agency: NIGMS NIH HHS, United States
    Id: P30 GM131944
  • Agency: NIGMS NIH HHS, United States
    Id: P20 GM103456
  • Agency: NIGMS NIH HHS, United States
    Id: P20 GM113134
  • Agency: NIMHD NIH HHS, United States
    Id: G12 MD007601
  • Agency: NIGMS NIH HHS, United States
    Id: P20 GM103457

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COX IV (3E11) Rabbit mAb (antibody)

RRID:AB_2085424

This monoclonal targets COX IV (3E11) Rabbit mAb

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β-Actin (13E5) Rabbit mAb (antibody)

RRID:AB_2223172

This monoclonal targets beta-Actin

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Glut4 (IF8) (antibody)

RRID:AB_629533

This monoclonal targets SLC2A4

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Akt1 (B-1) (antibody)

RRID:AB_626658

This monoclonal targets AKT1

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GLUT1 antibody (antibody)

RRID:AB_10837075

This polyclonal targets GLUT1

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ATP1A1 antibody (antibody)

RRID:AB_2227873

This polyclonal targets ATP1A1

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Phospho-AKT (Ser473) antibody (antibody)

RRID:AB_2782958

This monoclonal targets Phospho-AKT (Ser473)

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IRDye 800CW Goat anti-Rabbit IgG (antibody)

RRID:AB_621843

This polyclonal secondary targets IgG

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GAPDH antibody (antibody)

RRID:AB_2107436

This monoclonal targets GAPDH

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p-ERK 1/2 (pT202/pY204.22A) (antibody)

RRID:AB_10856869

This monoclonal targets p-ERK 1/2 (pT202/pY204.22A)

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Exo70 (D-6) (antibody)

RRID:AB_10843358

This monoclonal targets Exo70 (D-6)

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EXOC5 antibody (antibody)

RRID:AB_2101582

This polyclonal targets EXOC5

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EXOC1 antibody (antibody)

RRID:AB_2231500

This polyclonal targets EXOC1

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Dystrophin antibody (antibody)

RRID:AB_10640422

This polyclonal targets Dystrophin

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MYC tag antibody (antibody)

RRID:AB_2734122

This monoclonal targets MYC tag

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L6-GLUT-4myc (cell line)

RRID:CVCL_0P25

Cell line L6-GLUT-4myc is a Transformed cell line with a species of origin Rattus norvegicus (Rat)

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IRDye 800CW Goat anti-Rabbit IgG (antibody)

RRID:AB_621843

This polyclonal secondary targets IgG

View all literature mentions

β-Actin (13E5) Rabbit mAb (antibody)

RRID:AB_2223172

This monoclonal targets beta-Actin

View all literature mentions

L6-GLUT-4myc (cell line)

RRID:CVCL_0P25

Cell line L6-GLUT-4myc is a Transformed cell line with a species of origin Rattus norvegicus (Rat)

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IRDye 800CW Goat anti-Rabbit IgG (antibody)

RRID:AB_621843

This polyclonal secondary targets IgG

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Glut4 (IF8) (antibody)

RRID:AB_629533

This monoclonal targets SLC2A4

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GLUT1 antibody (antibody)

RRID:AB_10837075

This polyclonal targets GLUT1

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ATP1A1 antibody (antibody)

RRID:AB_2227873

This polyclonal targets ATP1A1

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p-ERK 1/2 (pT202/pY204.22A) (antibody)

RRID:AB_10856869

This monoclonal targets p-ERK 1/2 (pT202/pY204.22A)

View all literature mentions

Phospho-AKT (Ser473) antibody (antibody)

RRID:AB_2782958

This monoclonal targets Phospho-AKT (Ser473)

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MYC tag antibody (antibody)

RRID:AB_2734122

This monoclonal targets MYC tag

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GAPDH antibody (antibody)

RRID:AB_2107436

This monoclonal targets GAPDH

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Exo70 (D-6) (antibody)

RRID:AB_10843358

This monoclonal targets Exo70 (D-6)

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EXOC5 antibody (antibody)

RRID:AB_2101582

This polyclonal targets EXOC5

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EXOC1 antibody (antibody)

RRID:AB_2231500

This polyclonal targets EXOC1

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Dystrophin antibody (antibody)

RRID:AB_10640422

This polyclonal targets Dystrophin

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COX IV (3E11) Rabbit mAb (antibody)

RRID:AB_2085424

This monoclonal targets COX IV (3E11) Rabbit mAb

View all literature mentions

β-Actin (13E5) Rabbit mAb (antibody)

RRID:AB_2223172

This monoclonal targets beta-Actin

View all literature mentions

Akt1 (B-1) (antibody)

RRID:AB_626658

This monoclonal targets AKT1

View all literature mentions

MYC tag antibody (antibody)

RRID:AB_2734122

This monoclonal targets MYC tag

View all literature mentions