The physiological regulation of glucose flux into muscle in vivo

David H. Wasserman, Li Kang, Julio E. Ayala, Patrick T. Fueger, Robert S. Lee-Young

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Skeletal muscle glucose uptake increases dramatically in response to physical exercise. Moreover, skeletal muscle comprises the vast majority of insulin-sensitive tissue and is a site of dysregulation in the insulin-resistant state. The biochemical and histological composition of the muscle is well defined in a variety of species. However, the functional consequences of muscle biochemical and histological adaptations to physiological and pathophysiological conditions are not well understood. The physiological regulation of muscle glucose uptake is complex. Sites involved in the regulation of muscle glucose uptake are defined by a three-step process consisting of: (1) delivery of glucose to muscle, (2) transport of glucose into the muscle by GLUT4 and (3) phosphorylation of glucose within the muscle by a hexokinase (HK). Muscle blood flow, capillary recruitment and extracellular matrix characteristics determine glucose movement from the blood to the interstitium. Plasma membrane GLUT4 content determines glucose transport into the cell. Muscle HK activity, cellular HK compartmentalization and the concentration of the HK inhibitor glucose 6-phosphate determine the capacity to phosphorylate glucose. Phosphorylation of glucose is irreversible in muscle; therefore, with this reaction, glucose is trapped and the uptake process is complete. Emphasis has been placed on the role of the glucose transport step for glucose influx into muscle with the past assertion that membrane transport is rate limiting. More recent research definitively shows that the distributed control paradigm more accurately defines the regulation of muscle glucose uptake as each of the three steps that define this process are important sites of flux control.

Original languageEnglish
Pages (from-to)254-262
Number of pages9
JournalJournal of Experimental Biology
Volume214
Issue number2
DOIs
StatePublished - Jan 2011

Fingerprint

physiological regulation
glucose
muscle
Glucose
Muscles
muscles
Hexokinase
hexokinase
uptake mechanisms
regulation
skeletal muscle
Skeletal Muscle
phosphorylation
Phosphorylation
Insulin
Physiological Adaptation
blood
Glucose-6-Phosphate
membrane
glucose 6-phosphate

Keywords

  • Flux
  • Glucose
  • In vivo

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Physiology
  • Insect Science
  • Aquatic Science

Cite this

Wasserman, D. H., Kang, L., Ayala, J. E., Fueger, P. T., & Lee-Young, R. S. (2011). The physiological regulation of glucose flux into muscle in vivo. Journal of Experimental Biology, 214(2), 254-262. https://doi.org/10.1242/jeb.048041

The physiological regulation of glucose flux into muscle in vivo. / Wasserman, David H.; Kang, Li; Ayala, Julio E.; Fueger, Patrick T.; Lee-Young, Robert S.

In: Journal of Experimental Biology, Vol. 214, No. 2, 01.2011, p. 254-262.

Research output: Contribution to journalArticle

Wasserman, DH, Kang, L, Ayala, JE, Fueger, PT & Lee-Young, RS 2011, 'The physiological regulation of glucose flux into muscle in vivo', Journal of Experimental Biology, vol. 214, no. 2, pp. 254-262. https://doi.org/10.1242/jeb.048041
Wasserman DH, Kang L, Ayala JE, Fueger PT, Lee-Young RS. The physiological regulation of glucose flux into muscle in vivo. Journal of Experimental Biology. 2011 Jan;214(2):254-262. https://doi.org/10.1242/jeb.048041
Wasserman, David H. ; Kang, Li ; Ayala, Julio E. ; Fueger, Patrick T. ; Lee-Young, Robert S. / The physiological regulation of glucose flux into muscle in vivo. In: Journal of Experimental Biology. 2011 ; Vol. 214, No. 2. pp. 254-262.
@article{5cee3e0992d94641b4d3f46b0a9903cd,
title = "The physiological regulation of glucose flux into muscle in vivo",
abstract = "Skeletal muscle glucose uptake increases dramatically in response to physical exercise. Moreover, skeletal muscle comprises the vast majority of insulin-sensitive tissue and is a site of dysregulation in the insulin-resistant state. The biochemical and histological composition of the muscle is well defined in a variety of species. However, the functional consequences of muscle biochemical and histological adaptations to physiological and pathophysiological conditions are not well understood. The physiological regulation of muscle glucose uptake is complex. Sites involved in the regulation of muscle glucose uptake are defined by a three-step process consisting of: (1) delivery of glucose to muscle, (2) transport of glucose into the muscle by GLUT4 and (3) phosphorylation of glucose within the muscle by a hexokinase (HK). Muscle blood flow, capillary recruitment and extracellular matrix characteristics determine glucose movement from the blood to the interstitium. Plasma membrane GLUT4 content determines glucose transport into the cell. Muscle HK activity, cellular HK compartmentalization and the concentration of the HK inhibitor glucose 6-phosphate determine the capacity to phosphorylate glucose. Phosphorylation of glucose is irreversible in muscle; therefore, with this reaction, glucose is trapped and the uptake process is complete. Emphasis has been placed on the role of the glucose transport step for glucose influx into muscle with the past assertion that membrane transport is rate limiting. More recent research definitively shows that the distributed control paradigm more accurately defines the regulation of muscle glucose uptake as each of the three steps that define this process are important sites of flux control.",
keywords = "Flux, Glucose, In vivo",
author = "Wasserman, {David H.} and Li Kang and Ayala, {Julio E.} and Fueger, {Patrick T.} and Lee-Young, {Robert S.}",
year = "2011",
month = "1",
doi = "10.1242/jeb.048041",
language = "English",
volume = "214",
pages = "254--262",
journal = "Journal of Experimental Biology",
issn = "0022-0949",
publisher = "Company of Biologists Ltd",
number = "2",

}

TY - JOUR

T1 - The physiological regulation of glucose flux into muscle in vivo

AU - Wasserman, David H.

AU - Kang, Li

AU - Ayala, Julio E.

AU - Fueger, Patrick T.

AU - Lee-Young, Robert S.

PY - 2011/1

Y1 - 2011/1

N2 - Skeletal muscle glucose uptake increases dramatically in response to physical exercise. Moreover, skeletal muscle comprises the vast majority of insulin-sensitive tissue and is a site of dysregulation in the insulin-resistant state. The biochemical and histological composition of the muscle is well defined in a variety of species. However, the functional consequences of muscle biochemical and histological adaptations to physiological and pathophysiological conditions are not well understood. The physiological regulation of muscle glucose uptake is complex. Sites involved in the regulation of muscle glucose uptake are defined by a three-step process consisting of: (1) delivery of glucose to muscle, (2) transport of glucose into the muscle by GLUT4 and (3) phosphorylation of glucose within the muscle by a hexokinase (HK). Muscle blood flow, capillary recruitment and extracellular matrix characteristics determine glucose movement from the blood to the interstitium. Plasma membrane GLUT4 content determines glucose transport into the cell. Muscle HK activity, cellular HK compartmentalization and the concentration of the HK inhibitor glucose 6-phosphate determine the capacity to phosphorylate glucose. Phosphorylation of glucose is irreversible in muscle; therefore, with this reaction, glucose is trapped and the uptake process is complete. Emphasis has been placed on the role of the glucose transport step for glucose influx into muscle with the past assertion that membrane transport is rate limiting. More recent research definitively shows that the distributed control paradigm more accurately defines the regulation of muscle glucose uptake as each of the three steps that define this process are important sites of flux control.

AB - Skeletal muscle glucose uptake increases dramatically in response to physical exercise. Moreover, skeletal muscle comprises the vast majority of insulin-sensitive tissue and is a site of dysregulation in the insulin-resistant state. The biochemical and histological composition of the muscle is well defined in a variety of species. However, the functional consequences of muscle biochemical and histological adaptations to physiological and pathophysiological conditions are not well understood. The physiological regulation of muscle glucose uptake is complex. Sites involved in the regulation of muscle glucose uptake are defined by a three-step process consisting of: (1) delivery of glucose to muscle, (2) transport of glucose into the muscle by GLUT4 and (3) phosphorylation of glucose within the muscle by a hexokinase (HK). Muscle blood flow, capillary recruitment and extracellular matrix characteristics determine glucose movement from the blood to the interstitium. Plasma membrane GLUT4 content determines glucose transport into the cell. Muscle HK activity, cellular HK compartmentalization and the concentration of the HK inhibitor glucose 6-phosphate determine the capacity to phosphorylate glucose. Phosphorylation of glucose is irreversible in muscle; therefore, with this reaction, glucose is trapped and the uptake process is complete. Emphasis has been placed on the role of the glucose transport step for glucose influx into muscle with the past assertion that membrane transport is rate limiting. More recent research definitively shows that the distributed control paradigm more accurately defines the regulation of muscle glucose uptake as each of the three steps that define this process are important sites of flux control.

KW - Flux

KW - Glucose

KW - In vivo

UR - http://www.scopus.com/inward/record.url?scp=78651276331&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78651276331&partnerID=8YFLogxK

U2 - 10.1242/jeb.048041

DO - 10.1242/jeb.048041

M3 - Article

VL - 214

SP - 254

EP - 262

JO - Journal of Experimental Biology

JF - Journal of Experimental Biology

SN - 0022-0949

IS - 2

ER -