Effects of exercise and insulin on insulin signaling proteins in human skeletal muscle

Janice A. Koval, Katsumi Maezono, Mary Elizabeth Patti, Merri Pendergrass, Ralph A Defronzo, Lawrence J. Mandarino

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Insulin and exercise independently increase glucose metabolism in muscle. Moreover, exercise training or a prior bout of exercise increases insulin-stimulated glucose uptake in resting skeletal muscle. The present study was undertaken to compare how physiological hyperinsulinemia and moderate intensity aerobic exercise affect the tyrosine phosphorylation state and activity of insulin signaling molecules in healthy, physically inactive volunteers. Subjects had biopsies of the vastus lateralis muscle before and immediately after 30 min of either hyperinsulinemia (euglycemic insulin clamp) or moderate-intensity exercise on a cycle ergometer (~60% of V̇O(2max)). Insulin receptor and IRS-1 tyrosine phosphorylation, association of the p85 regulatory subunit of PI 3-kinase with IRS-1, IRS-1 associated PI 3-kinase activity, and glycogen synthase activity were determined in muscle biopsy specimens taken from healthy subjects before and after insulin or exercise. Physiological hyperinsulinemia increased the rate of glucose disposal from 11.4 ± 1.5 to 25.6 ± 6.7 μmol · kg-1 · min-1 (P < 0.01), insulin receptor and IRS-1 tyrosine phosphorylation (173 ± 19% and 159 ± 35% of basal values, respectively, P < 0.05), association of the p85 regulatory subunit of PI 3-kinase with IRS-1 (159 ± 10%, P < 0.05), and glycogen synthase fractional velocity (136 ± 11%, P < 0.01). Exercise also increased glucose disposal, from 10.4 ± 0.5 to 15.6 ± 1.7 μmol · kg-1 · min-1 (P < 0.01) and glycogen synthase fractional velocity (253 ± 35% of basal, P < 0.01). The exercise-induced increase in glycogen synthase was greater than that due to insulin (P < 0.05). In contrast to insulin, exercise decreased tyrosine phosphorylation of the insulin receptor to 72 ± 10% of basal values (P < 0.05 vs basal and P < 0.05 vs insulin) and had no effect on IRS-1 tyrosine phosphorylation, or association of p85 with IRS-1. The exercise-induced decreased insulin receptor tyrosine phosphorylation could explain the well-known effect of exercise to enhance the sensitivity of muscle to insulin.

Original languageEnglish (US)
Pages (from-to)998-1004
Number of pages7
JournalMedicine and Science in Sports and Exercise
Volume31
Issue number7
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Skeletal Muscle
Exercise
Insulin
Tyrosine
Glycogen Synthase
Proteins
Insulin Receptor
Phosphorylation
Hyperinsulinism
Phosphatidylinositol 3-Kinases
Glucose
Muscles
Biopsy
Glucose Clamp Technique
Quadriceps Muscle
Volunteers
Healthy Volunteers

Keywords

  • Exercise
  • Insulin Receptor
  • Insulin Signaling
  • Skeletal Muscle

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Physical Therapy, Sports Therapy and Rehabilitation
  • Orthopedics and Sports Medicine

Cite this

Effects of exercise and insulin on insulin signaling proteins in human skeletal muscle. / Koval, Janice A.; Maezono, Katsumi; Patti, Mary Elizabeth; Pendergrass, Merri; Defronzo, Ralph A; Mandarino, Lawrence J.

In: Medicine and Science in Sports and Exercise, Vol. 31, No. 7, 1999, p. 998-1004.

Research output: Contribution to journalArticle

Koval, Janice A. ; Maezono, Katsumi ; Patti, Mary Elizabeth ; Pendergrass, Merri ; Defronzo, Ralph A ; Mandarino, Lawrence J. / Effects of exercise and insulin on insulin signaling proteins in human skeletal muscle. In: Medicine and Science in Sports and Exercise. 1999 ; Vol. 31, No. 7. pp. 998-1004.
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