Herpud1 impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca2+-calcineurin-Akt axis

Mario Navarro-Marquez, Natalia Torrealba, Rodrigo Troncoso, Cesar Vásquez-Trincado, Marcelo Rodriguez, Pablo E. Morales, Elisa Villalobos, Yuka Eura, Lorena Garcia, Mario Chiong, Amira Klip, Enrique Jaimovich, Koichi Kokame, Sergio Lavandero

Resultado de la investigación: Article

3 Citas (Scopus)

Resumen

Skeletal muscle plays a central role in insulin-controlled glucose homeostasis. The molecular mechanisms related to insulin resistance in this tissue are incompletely understood. Herpud1 is an endoplasmic reticulum membrane protein that maintains intracellular Ca2+ homeostasis under stress conditions. It has recently been reported that Herpud1-knockout mice display intolerance to a glucose load without showing altered insulin secretion. The functions of Herpud1 in skeletal muscle also remain unknown. Based on these findings, we propose that Herpud1 is necessary for insulin-dependent glucose disposal in skeletal muscle. Here we show that Herpud1 silencing decreased insulin-dependent glucose uptake, GLUT4 translocation to the plasma membrane, and Akt Ser473 phosphorylation in cultured L6 myotubes. A decrease in insulin-induced Akt Ser473 phosphorylation was observed in soleus but not in extensor digitorum longus muscle samples from Herpud1-knockout mice. Herpud1 knockdown increased the IP3R-dependent cytosolic Ca2+ response and the activity of Ca2+-dependent serine/threonine phosphatase calcineurin in L6 cells. Calcineurin decreased insulin-dependent Akt phosphorylation and glucose uptake. Moreover, calcineurin inhibition restored the insulin response in Herpud1-depleted L6 cells. Based on these findings, we conclude that Herpud1 is necessary for adequate insulin-induced glucose uptake due to its role in Ca2+/calcineurin regulation in L6 myotubes.

Idioma originalEnglish
Páginas (desde-hasta)1653-1662
Número de páginas10
PublicaciónBiochimica et Biophysica Acta - Molecular Basis of Disease
Volumen1864
N.º5
DOI
EstadoPublished - may 2018
Publicado de forma externa

Huella dactilar

Calcineurin
Muscle Cells
Skeletal Muscle
Insulin
Glucose
Skeletal Muscle Fibers
Phosphorylation
Knockout Mice
Homeostasis
Phosphoprotein Phosphatases
Endoplasmic Reticulum
Insulin Resistance
Membrane Proteins
Cell Membrane
Muscles

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Citar esto

Navarro-Marquez, M., Torrealba, N., Troncoso, R., Vásquez-Trincado, C., Rodriguez, M., Morales, P. E., ... Lavandero, S. (2018). Herpud1 impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca2+-calcineurin-Akt axis. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1864(5), 1653-1662. https://doi.org/10.1016/j.bbadis.2018.02.018
Navarro-Marquez, Mario ; Torrealba, Natalia ; Troncoso, Rodrigo ; Vásquez-Trincado, Cesar ; Rodriguez, Marcelo ; Morales, Pablo E. ; Villalobos, Elisa ; Eura, Yuka ; Garcia, Lorena ; Chiong, Mario ; Klip, Amira ; Jaimovich, Enrique ; Kokame, Koichi ; Lavandero, Sergio. / Herpud1 impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca2+-calcineurin-Akt axis. En: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2018 ; Vol. 1864, N.º 5. pp. 1653-1662.
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title = "Herpud1 impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca2+-calcineurin-Akt axis",
abstract = "Skeletal muscle plays a central role in insulin-controlled glucose homeostasis. The molecular mechanisms related to insulin resistance in this tissue are incompletely understood. Herpud1 is an endoplasmic reticulum membrane protein that maintains intracellular Ca2+ homeostasis under stress conditions. It has recently been reported that Herpud1-knockout mice display intolerance to a glucose load without showing altered insulin secretion. The functions of Herpud1 in skeletal muscle also remain unknown. Based on these findings, we propose that Herpud1 is necessary for insulin-dependent glucose disposal in skeletal muscle. Here we show that Herpud1 silencing decreased insulin-dependent glucose uptake, GLUT4 translocation to the plasma membrane, and Akt Ser473 phosphorylation in cultured L6 myotubes. A decrease in insulin-induced Akt Ser473 phosphorylation was observed in soleus but not in extensor digitorum longus muscle samples from Herpud1-knockout mice. Herpud1 knockdown increased the IP3R-dependent cytosolic Ca2+ response and the activity of Ca2+-dependent serine/threonine phosphatase calcineurin in L6 cells. Calcineurin decreased insulin-dependent Akt phosphorylation and glucose uptake. Moreover, calcineurin inhibition restored the insulin response in Herpud1-depleted L6 cells. Based on these findings, we conclude that Herpud1 is necessary for adequate insulin-induced glucose uptake due to its role in Ca2+/calcineurin regulation in L6 myotubes.",
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author = "Mario Navarro-Marquez and Natalia Torrealba and Rodrigo Troncoso and Cesar V{\'a}squez-Trincado and Marcelo Rodriguez and Morales, {Pablo E.} and Elisa Villalobos and Yuka Eura and Lorena Garcia and Mario Chiong and Amira Klip and Enrique Jaimovich and Koichi Kokame and Sergio Lavandero",
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Navarro-Marquez, M, Torrealba, N, Troncoso, R, Vásquez-Trincado, C, Rodriguez, M, Morales, PE, Villalobos, E, Eura, Y, Garcia, L, Chiong, M, Klip, A, Jaimovich, E, Kokame, K & Lavandero, S 2018, 'Herpud1 impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca2+-calcineurin-Akt axis', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1864, n.º 5, pp. 1653-1662. https://doi.org/10.1016/j.bbadis.2018.02.018

Herpud1 impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca2+-calcineurin-Akt axis. / Navarro-Marquez, Mario; Torrealba, Natalia; Troncoso, Rodrigo; Vásquez-Trincado, Cesar; Rodriguez, Marcelo; Morales, Pablo E.; Villalobos, Elisa; Eura, Yuka; Garcia, Lorena; Chiong, Mario; Klip, Amira; Jaimovich, Enrique; Kokame, Koichi; Lavandero, Sergio.

En: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1864, N.º 5, 05.2018, p. 1653-1662.

Resultado de la investigación: Article

TY - JOUR

T1 - Herpud1 impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca2+-calcineurin-Akt axis

AU - Navarro-Marquez, Mario

AU - Torrealba, Natalia

AU - Troncoso, Rodrigo

AU - Vásquez-Trincado, Cesar

AU - Rodriguez, Marcelo

AU - Morales, Pablo E.

AU - Villalobos, Elisa

AU - Eura, Yuka

AU - Garcia, Lorena

AU - Chiong, Mario

AU - Klip, Amira

AU - Jaimovich, Enrique

AU - Kokame, Koichi

AU - Lavandero, Sergio

PY - 2018/5

Y1 - 2018/5

N2 - Skeletal muscle plays a central role in insulin-controlled glucose homeostasis. The molecular mechanisms related to insulin resistance in this tissue are incompletely understood. Herpud1 is an endoplasmic reticulum membrane protein that maintains intracellular Ca2+ homeostasis under stress conditions. It has recently been reported that Herpud1-knockout mice display intolerance to a glucose load without showing altered insulin secretion. The functions of Herpud1 in skeletal muscle also remain unknown. Based on these findings, we propose that Herpud1 is necessary for insulin-dependent glucose disposal in skeletal muscle. Here we show that Herpud1 silencing decreased insulin-dependent glucose uptake, GLUT4 translocation to the plasma membrane, and Akt Ser473 phosphorylation in cultured L6 myotubes. A decrease in insulin-induced Akt Ser473 phosphorylation was observed in soleus but not in extensor digitorum longus muscle samples from Herpud1-knockout mice. Herpud1 knockdown increased the IP3R-dependent cytosolic Ca2+ response and the activity of Ca2+-dependent serine/threonine phosphatase calcineurin in L6 cells. Calcineurin decreased insulin-dependent Akt phosphorylation and glucose uptake. Moreover, calcineurin inhibition restored the insulin response in Herpud1-depleted L6 cells. Based on these findings, we conclude that Herpud1 is necessary for adequate insulin-induced glucose uptake due to its role in Ca2+/calcineurin regulation in L6 myotubes.

AB - Skeletal muscle plays a central role in insulin-controlled glucose homeostasis. The molecular mechanisms related to insulin resistance in this tissue are incompletely understood. Herpud1 is an endoplasmic reticulum membrane protein that maintains intracellular Ca2+ homeostasis under stress conditions. It has recently been reported that Herpud1-knockout mice display intolerance to a glucose load without showing altered insulin secretion. The functions of Herpud1 in skeletal muscle also remain unknown. Based on these findings, we propose that Herpud1 is necessary for insulin-dependent glucose disposal in skeletal muscle. Here we show that Herpud1 silencing decreased insulin-dependent glucose uptake, GLUT4 translocation to the plasma membrane, and Akt Ser473 phosphorylation in cultured L6 myotubes. A decrease in insulin-induced Akt Ser473 phosphorylation was observed in soleus but not in extensor digitorum longus muscle samples from Herpud1-knockout mice. Herpud1 knockdown increased the IP3R-dependent cytosolic Ca2+ response and the activity of Ca2+-dependent serine/threonine phosphatase calcineurin in L6 cells. Calcineurin decreased insulin-dependent Akt phosphorylation and glucose uptake. Moreover, calcineurin inhibition restored the insulin response in Herpud1-depleted L6 cells. Based on these findings, we conclude that Herpud1 is necessary for adequate insulin-induced glucose uptake due to its role in Ca2+/calcineurin regulation in L6 myotubes.

KW - Akt

KW - Calcineurin

KW - Calcium

KW - Herpud1

KW - Insulin

KW - Skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=85042689917&partnerID=8YFLogxK

U2 - 10.1016/j.bbadis.2018.02.018

DO - 10.1016/j.bbadis.2018.02.018

M3 - Article

C2 - 29486284

AN - SCOPUS:85042689917

VL - 1864

SP - 1653

EP - 1662

JO - Biochimica et Biophysica Acta - Molecular Basis of Disease

JF - Biochimica et Biophysica Acta - Molecular Basis of Disease

SN - 0925-4439

IS - 5

ER -