PMID- 10658053
OWN - NLM
STAT- MEDLINE
DCOM- 20000303
LR  - 20171213
IS  - 8750-7587 (Print)
IS  - 0161-7567 (Linking)
VI  - 88
IP  - 2
DP  - 2000 Feb
TI  - Regular exercise enhances insulin activation of IRS-1-associated PI3-kinase in 
      human skeletal muscle.
PG  - 797-803
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 O(2) uptake (VO(2 max)) 
      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, VO(2 max) of 44.4 +/- 2.7 ml. kg(-1). min(-1)). A 
      [6, 6-(2)H]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 (VO(2 max)) 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.
FAU - Kirwan, J P
AU  - Kirwan JP
AD  - Departments of Reproductive Biology and Nutrition, Case Western Reserve 
      University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio 
      44109, USA. jkirwan@metrohealth.org
FAU - del Aguila, L F
AU  - del Aguila LF
FAU - Hernandez, J M
AU  - Hernandez JM
FAU - Williamson, D L
AU  - Williamson DL
FAU - O'Gorman, D J
AU  - O'Gorman DJ
FAU - Lewis, R
AU  - Lewis R
FAU - Krishnan, R K
AU  - Krishnan RK
LA  - eng
GR  - AG-12834/AG/NIA NIH HHS/United States
GR  - P41-RR-00959/RR/NCRR NIH HHS/United States
GR  - RR-10732/RR/NCRR NIH HHS/United States
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 0 (Blood Glucose)
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adult
MH  - Blood Glucose/drug effects/metabolism
MH  - Enzyme Activation/drug effects
MH  - Exercise/*physiology
MH  - Female
MH  - Glucose/pharmacology
MH  - Humans
MH  - Infusions, Intravenous
MH  - Insulin/blood/*pharmacology
MH  - Insulin Receptor Substrate Proteins
MH  - Male
MH  - Muscle, Skeletal/*drug effects/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoproteins/*metabolism
EDAT- 2000/02/05 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/02/05 09:00
PHST- 2000/02/05 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/02/05 09:00 [entrez]
AID - 10.1152/jappl.2000.88.2.797 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2000 Feb;88(2):797-803. doi: 10.1152/jappl.2000.88.2.797.