Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects

Jørgen Jensen, Puntip Tantiwong, Jorid T. Stuenæs, Marjorie Molina-Carrion, Ralph A Defronzo, Kei Sakamoto, Nicolas Musi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of V̇O 2max). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS K m for UDP-glucose from ≈0.5 to ≈0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50-70% (Ser 641, Ser 645, and Ser 645,649,653,657), and phosphorylation of these sites remained decreased after 3.5 h; Ser 7 phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased K m for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume303
Issue number1
DOIs
StatePublished - Jul 1 2012

Fingerprint

Glycogen Synthase
Exercise
Muscles
Phosphorylation
Insulin
Uridine Diphosphate Glucose
Glucose
Quadriceps Muscle
Glycogen
Serine
Skeletal Muscle

Keywords

  • Insulin resistance

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects. / Jensen, Jørgen; Tantiwong, Puntip; Stuenæs, Jorid T.; Molina-Carrion, Marjorie; Defronzo, Ralph A; Sakamoto, Kei; Musi, Nicolas.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 303, No. 1, 01.07.2012.

Research output: Contribution to journalArticle

Jensen, Jørgen ; Tantiwong, Puntip ; Stuenæs, Jorid T. ; Molina-Carrion, Marjorie ; Defronzo, Ralph A ; Sakamoto, Kei ; Musi, Nicolas. / Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects. In: American Journal of Physiology - Endocrinology and Metabolism. 2012 ; Vol. 303, No. 1.
@article{5e92b9c4f5e84073b44ccb272acbc977,
title = "Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects",
abstract = "Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70{\%} of V̇O 2max). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS K m for UDP-glucose from ≈0.5 to ≈0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50-70{\%} (Ser 641, Ser 645, and Ser 645,649,653,657), and phosphorylation of these sites remained decreased after 3.5 h; Ser 7 phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased K m for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects.",
keywords = "Insulin resistance",
author = "J{\o}rgen Jensen and Puntip Tantiwong and Stuen{\ae}s, {Jorid T.} and Marjorie Molina-Carrion and Defronzo, {Ralph A} and Kei Sakamoto and Nicolas Musi",
year = "2012",
month = "7",
day = "1",
doi = "10.1152/ajpendo.00658.2011",
language = "English (US)",
volume = "303",
journal = "American Journal of Physiology - Renal Physiology",
issn = "0363-6127",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects

AU - Jensen, Jørgen

AU - Tantiwong, Puntip

AU - Stuenæs, Jorid T.

AU - Molina-Carrion, Marjorie

AU - Defronzo, Ralph A

AU - Sakamoto, Kei

AU - Musi, Nicolas

PY - 2012/7/1

Y1 - 2012/7/1

N2 - Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of V̇O 2max). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS K m for UDP-glucose from ≈0.5 to ≈0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50-70% (Ser 641, Ser 645, and Ser 645,649,653,657), and phosphorylation of these sites remained decreased after 3.5 h; Ser 7 phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased K m for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects.

AB - Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of V̇O 2max). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS K m for UDP-glucose from ≈0.5 to ≈0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50-70% (Ser 641, Ser 645, and Ser 645,649,653,657), and phosphorylation of these sites remained decreased after 3.5 h; Ser 7 phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased K m for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects.

KW - Insulin resistance

UR - http://www.scopus.com/inward/record.url?scp=84863714743&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863714743&partnerID=8YFLogxK

U2 - 10.1152/ajpendo.00658.2011

DO - 10.1152/ajpendo.00658.2011

M3 - Article

C2 - 22510711

AN - SCOPUS:84863714743

VL - 303

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 0363-6127

IS - 1

ER -