Regular exercise enhances insulin activation of IRS-1-associated PI3- kinase in human skeletal muscle

John P. Kirwan, Luis F. Del Aguila, Jazmir M. Hernandez, David L. Williamson, IV, Donal J. O'Gorman, Rebecca Lewis, Raj K. Krishnan

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Insulin action in skeletal muscle is enhanced by regular exercise. Whether insulin signaling in human skeletal muscle is affected by habitual exercise is not well understood. Phosphatidylinositol 3-kinase (PI3-kinase) activation is an important step in the insulin-signaling pathway and appears to regulate glucose metabolism via GLUT-4 translocation in skeletal muscle. To examine the effects of regular exercise on PI3-kinase activation, 2-h hyperinsulinemic (40 mU · m-2 · min-1)-euglycemic (5.0 mM) clamps were performed on eight healthy exercise-trained [24 ± 1 yr, 71.8 ± 2.0 kg, maximal O2 uptake (V̇O(2max)) of 56.1 ± 2.5 ml · kg-1 · min-1] and eight healthy sedentary men and women (24 ± 1 yr, 64.7 ± 4.4 kg, V̇O(2max) of 44.4 ± 2.7 ml · kg-1 · min-1). A [6,6-2H] glucose tracer was used to measure hepatic glucose output. A muscle biopsy was obtained from the vastus lateralis muscle at basal and at 2 h of hyperinsulinemia to measure insulin receptor substrate-1(IRS-1)-associated PI3-kinase activation. Insulin concentrations during hyperinsulinemia were similar for both groups (293 ± 22 and 311 ± 22 pM for trained and sedentary, respectively). Insulin- mediated glucose disposal rates (GDR) were greater (P < 0.05) in the exercise-trained compared with the sedentary control group (9.22 ± 0.95 vs. 6.36 ± 0.57 mg · kg fat-free mass-1 · min-1). Insulin-stimulated PI3- kinase activation was also greater (P < 0.004) in the trained compared with the sedentary group (3.8 ± 0.5- vs. 1.8 ± 0.2-fold increase from basal). Endurance capacity (V̇O(2max)) was positively correlated with PI3-kinase activation (r = 0.53, P < 0.04). There was no correlation between PI3-kinase and muscle morphology. However, increases in GDR were positively related to PI3-kinase activation (r = 0.60, P < 0.02). We conclude that regular exercise leads to greater insulin-stimulated IRS-1-associated PI3-kinase activation in human skeletal muscle, thus facilitating enhanced insulin-mediated glucose uptake.

Original languageEnglish (US)
Pages (from-to)797-803
Number of pages7
JournalJournal of Applied Physiology
Volume88
Issue number2
StatePublished - Feb 1 2000

Fingerprint

Insulin Receptor Substrate Proteins
Phosphatidylinositol 3-Kinase
Phosphatidylinositol 3-Kinases
Skeletal Muscle
Exercise
Insulin
Glucose
Hyperinsulinism
Muscles
Quadriceps Muscle
Fats
Biopsy
Control Groups
Liver

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Kirwan, J. P., Del Aguila, L. F., Hernandez, J. M., Williamson, IV, D. L., O'Gorman, D. J., Lewis, R., & Krishnan, R. K. (2000). Regular exercise enhances insulin activation of IRS-1-associated PI3- kinase in human skeletal muscle. Journal of Applied Physiology, 88(2), 797-803.
Kirwan, John P. ; Del Aguila, Luis F. ; Hernandez, Jazmir M. ; Williamson, IV, David L. ; O'Gorman, Donal J. ; Lewis, Rebecca ; Krishnan, Raj K. / Regular exercise enhances insulin activation of IRS-1-associated PI3- kinase in human skeletal muscle. In: Journal of Applied Physiology. 2000 ; Vol. 88, No. 2. pp. 797-803.
@article{17442b102d464a14b6d3d915d5c212ed,
title = "Regular exercise enhances insulin activation of IRS-1-associated PI3- kinase in human skeletal muscle",
abstract = "Insulin action in skeletal muscle is enhanced by regular exercise. Whether insulin signaling in human skeletal muscle is affected by habitual exercise is not well understood. Phosphatidylinositol 3-kinase (PI3-kinase) activation is an important step in the insulin-signaling pathway and appears to regulate glucose metabolism via GLUT-4 translocation in skeletal muscle. To examine the effects of regular exercise on PI3-kinase activation, 2-h hyperinsulinemic (40 mU · m-2 · min-1)-euglycemic (5.0 mM) clamps were performed on eight healthy exercise-trained [24 ± 1 yr, 71.8 ± 2.0 kg, maximal O2 uptake (V̇O(2max)) of 56.1 ± 2.5 ml · kg-1 · min-1] and eight healthy sedentary men and women (24 ± 1 yr, 64.7 ± 4.4 kg, V̇O(2max) of 44.4 ± 2.7 ml · kg-1 · min-1). A [6,6-2H] glucose tracer was used to measure hepatic glucose output. A muscle biopsy was obtained from the vastus lateralis muscle at basal and at 2 h of hyperinsulinemia to measure insulin receptor substrate-1(IRS-1)-associated PI3-kinase activation. Insulin concentrations during hyperinsulinemia were similar for both groups (293 ± 22 and 311 ± 22 pM for trained and sedentary, respectively). Insulin- mediated glucose disposal rates (GDR) were greater (P < 0.05) in the exercise-trained compared with the sedentary control group (9.22 ± 0.95 vs. 6.36 ± 0.57 mg · kg fat-free mass-1 · min-1). Insulin-stimulated PI3- kinase activation was also greater (P < 0.004) in the trained compared with the sedentary group (3.8 ± 0.5- vs. 1.8 ± 0.2-fold increase from basal). Endurance capacity (V̇O(2max)) was positively correlated with PI3-kinase activation (r = 0.53, P < 0.04). There was no correlation between PI3-kinase and muscle morphology. However, increases in GDR were positively related to PI3-kinase activation (r = 0.60, P < 0.02). We conclude that regular exercise leads to greater insulin-stimulated IRS-1-associated PI3-kinase activation in human skeletal muscle, thus facilitating enhanced insulin-mediated glucose uptake.",
author = "Kirwan, {John P.} and {Del Aguila}, {Luis F.} and Hernandez, {Jazmir M.} and {Williamson, IV}, {David L.} and O'Gorman, {Donal J.} and Rebecca Lewis and Krishnan, {Raj K.}",
year = "2000",
month = "2",
day = "1",
language = "English (US)",
volume = "88",
pages = "797--803",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "2",

}

Kirwan, JP, Del Aguila, LF, Hernandez, JM, Williamson, IV, DL, O'Gorman, DJ, Lewis, R & Krishnan, RK 2000, 'Regular exercise enhances insulin activation of IRS-1-associated PI3- kinase in human skeletal muscle', Journal of Applied Physiology, vol. 88, no. 2, pp. 797-803.

Regular exercise enhances insulin activation of IRS-1-associated PI3- kinase in human skeletal muscle. / Kirwan, John P.; Del Aguila, Luis F.; Hernandez, Jazmir M.; Williamson, IV, David L.; O'Gorman, Donal J.; Lewis, Rebecca; Krishnan, Raj K.

In: Journal of Applied Physiology, Vol. 88, No. 2, 01.02.2000, p. 797-803.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Regular exercise enhances insulin activation of IRS-1-associated PI3- kinase in human skeletal muscle

AU - Kirwan, John P.

AU - Del Aguila, Luis F.

AU - Hernandez, Jazmir M.

AU - Williamson, IV, David L.

AU - O'Gorman, Donal J.

AU - Lewis, Rebecca

AU - Krishnan, Raj K.

PY - 2000/2/1

Y1 - 2000/2/1

N2 - Insulin action in skeletal muscle is enhanced by regular exercise. Whether insulin signaling in human skeletal muscle is affected by habitual exercise is not well understood. Phosphatidylinositol 3-kinase (PI3-kinase) activation is an important step in the insulin-signaling pathway and appears to regulate glucose metabolism via GLUT-4 translocation in skeletal muscle. To examine the effects of regular exercise on PI3-kinase activation, 2-h hyperinsulinemic (40 mU · m-2 · min-1)-euglycemic (5.0 mM) clamps were performed on eight healthy exercise-trained [24 ± 1 yr, 71.8 ± 2.0 kg, maximal O2 uptake (V̇O(2max)) of 56.1 ± 2.5 ml · kg-1 · min-1] and eight healthy sedentary men and women (24 ± 1 yr, 64.7 ± 4.4 kg, V̇O(2max) of 44.4 ± 2.7 ml · kg-1 · min-1). A [6,6-2H] glucose tracer was used to measure hepatic glucose output. A muscle biopsy was obtained from the vastus lateralis muscle at basal and at 2 h of hyperinsulinemia to measure insulin receptor substrate-1(IRS-1)-associated PI3-kinase activation. Insulin concentrations during hyperinsulinemia were similar for both groups (293 ± 22 and 311 ± 22 pM for trained and sedentary, respectively). Insulin- mediated glucose disposal rates (GDR) were greater (P < 0.05) in the exercise-trained compared with the sedentary control group (9.22 ± 0.95 vs. 6.36 ± 0.57 mg · kg fat-free mass-1 · min-1). Insulin-stimulated PI3- kinase activation was also greater (P < 0.004) in the trained compared with the sedentary group (3.8 ± 0.5- vs. 1.8 ± 0.2-fold increase from basal). Endurance capacity (V̇O(2max)) was positively correlated with PI3-kinase activation (r = 0.53, P < 0.04). There was no correlation between PI3-kinase and muscle morphology. However, increases in GDR were positively related to PI3-kinase activation (r = 0.60, P < 0.02). We conclude that regular exercise leads to greater insulin-stimulated IRS-1-associated PI3-kinase activation in human skeletal muscle, thus facilitating enhanced insulin-mediated glucose uptake.

AB - Insulin action in skeletal muscle is enhanced by regular exercise. Whether insulin signaling in human skeletal muscle is affected by habitual exercise is not well understood. Phosphatidylinositol 3-kinase (PI3-kinase) activation is an important step in the insulin-signaling pathway and appears to regulate glucose metabolism via GLUT-4 translocation in skeletal muscle. To examine the effects of regular exercise on PI3-kinase activation, 2-h hyperinsulinemic (40 mU · m-2 · min-1)-euglycemic (5.0 mM) clamps were performed on eight healthy exercise-trained [24 ± 1 yr, 71.8 ± 2.0 kg, maximal O2 uptake (V̇O(2max)) of 56.1 ± 2.5 ml · kg-1 · min-1] and eight healthy sedentary men and women (24 ± 1 yr, 64.7 ± 4.4 kg, V̇O(2max) of 44.4 ± 2.7 ml · kg-1 · min-1). A [6,6-2H] glucose tracer was used to measure hepatic glucose output. A muscle biopsy was obtained from the vastus lateralis muscle at basal and at 2 h of hyperinsulinemia to measure insulin receptor substrate-1(IRS-1)-associated PI3-kinase activation. Insulin concentrations during hyperinsulinemia were similar for both groups (293 ± 22 and 311 ± 22 pM for trained and sedentary, respectively). Insulin- mediated glucose disposal rates (GDR) were greater (P < 0.05) in the exercise-trained compared with the sedentary control group (9.22 ± 0.95 vs. 6.36 ± 0.57 mg · kg fat-free mass-1 · min-1). Insulin-stimulated PI3- kinase activation was also greater (P < 0.004) in the trained compared with the sedentary group (3.8 ± 0.5- vs. 1.8 ± 0.2-fold increase from basal). Endurance capacity (V̇O(2max)) was positively correlated with PI3-kinase activation (r = 0.53, P < 0.04). There was no correlation between PI3-kinase and muscle morphology. However, increases in GDR were positively related to PI3-kinase activation (r = 0.60, P < 0.02). We conclude that regular exercise leads to greater insulin-stimulated IRS-1-associated PI3-kinase activation in human skeletal muscle, thus facilitating enhanced insulin-mediated glucose uptake.

UR - http://www.scopus.com/inward/record.url?scp=0033977444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033977444&partnerID=8YFLogxK

M3 - Article

C2 - 10658053

AN - SCOPUS:0033977444

VL - 88

SP - 797

EP - 803

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 2

ER -