Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity

Meredith A. Hawkins, Meizhu Hu, Jinghua Yu, Howard Eder, Patricia Vuguin, Li She, Nir Barzilai, Margarita Leiser, Jonathan M. Backer, Luciano Rossetti

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The impact of increased Glen availability on insulin-stimulated p85/p110 phosphatidylinositol 3-kinase (PI3K) activity in skeletal muscle was examined in relation to GlcN-induced defects in peripheral insulin action. Primed continuous GlcN infusion (750 μmol/kg bolus; 30 μmol/kg·min) in conscious rats limited both maximal stimulation of muscle PI3K by acute insulin (I) (1 unit/kg) bolus (I + GlcN = 1.9-fold versus saline = 3.3-fold above fasting levels; p < 0.01) and chronic activation of PI3K following 3-h euglycemic, hyperinsulinemic (18 milliunits/kg·min) clamp studies (I + GlcN = 1.2-fold versus saline = 2.6-fold stimulation;p < 0.01). To determine the time course of GlcN-induced defects in insulin-stimulated PI3K activity and peripheral insulin action, GlcN was administered for 30, 60, 90, or 120 min during 2-h euglycemic, hyperinsulinemic clamp studies. Activation of muscle PI3K by insulin was attenuated following only 30 rain of GlcN infusion (GlcN 30 min = 1.5-fold versus saline = 2.5-fold stimulation; p < 0.05). In contrast, the first impairment in insulin-mediated glucose uptake (Rd) developed following 110 min of GlcN infusion (110 min = 39.9 ± 1.8 versus 30 min = 42.8 ± 1.4 mg/kg·min, p < 0.05). However, the ability of insulin to stimulate phosphatidylinositol 3,4,5-trisphosphate production and to activate glycogen synthase in skeletal muscle was preserved following up to 180 min of GlcN infusion. Thus, increased GlcN availability induced (a) profound and early inhibition of proximal insulin signaling at the level of PI3K and (b) delayed effects on insulin-mediated glucose uptake, yet (c) complete sparing of insulin-mediated glycogen synthase activation. The pattern and time sequence of GlcN-induced defects suggest that the etiology of peripheral insulin resistance may be distinct from the rapid and marked impairment in insulin signaling.

Original languageEnglish (US)
Pages (from-to)31312-31319
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number44
DOIs
StatePublished - Oct 29 1999

Fingerprint

Phosphatidylinositol 3-Kinase
Glucosamine
Metabolism
Insulin
Glucose
Muscle
Glycogen Synthase
Chemical activation
Clamping devices
Defects
Skeletal Muscle
Availability
Muscles
Aptitude
Glucose Clamp Technique
Rain
Vascular Resistance
Insulin Resistance

ASJC Scopus subject areas

  • Biochemistry

Cite this

Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity. / Hawkins, Meredith A.; Hu, Meizhu; Yu, Jinghua; Eder, Howard; Vuguin, Patricia; She, Li; Barzilai, Nir; Leiser, Margarita; Backer, Jonathan M.; Rossetti, Luciano.

In: Journal of Biological Chemistry, Vol. 274, No. 44, 29.10.1999, p. 31312-31319.

Research output: Contribution to journalArticle

Hawkins, Meredith A. ; Hu, Meizhu ; Yu, Jinghua ; Eder, Howard ; Vuguin, Patricia ; She, Li ; Barzilai, Nir ; Leiser, Margarita ; Backer, Jonathan M. ; Rossetti, Luciano. / Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 44. pp. 31312-31319.
@article{88b1c4bf61a246039fd47861baca4598,
title = "Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity",
abstract = "The impact of increased Glen availability on insulin-stimulated p85/p110 phosphatidylinositol 3-kinase (PI3K) activity in skeletal muscle was examined in relation to GlcN-induced defects in peripheral insulin action. Primed continuous GlcN infusion (750 μmol/kg bolus; 30 μmol/kg·min) in conscious rats limited both maximal stimulation of muscle PI3K by acute insulin (I) (1 unit/kg) bolus (I + GlcN = 1.9-fold versus saline = 3.3-fold above fasting levels; p < 0.01) and chronic activation of PI3K following 3-h euglycemic, hyperinsulinemic (18 milliunits/kg·min) clamp studies (I + GlcN = 1.2-fold versus saline = 2.6-fold stimulation;p < 0.01). To determine the time course of GlcN-induced defects in insulin-stimulated PI3K activity and peripheral insulin action, GlcN was administered for 30, 60, 90, or 120 min during 2-h euglycemic, hyperinsulinemic clamp studies. Activation of muscle PI3K by insulin was attenuated following only 30 rain of GlcN infusion (GlcN 30 min = 1.5-fold versus saline = 2.5-fold stimulation; p < 0.05). In contrast, the first impairment in insulin-mediated glucose uptake (Rd) developed following 110 min of GlcN infusion (110 min = 39.9 ± 1.8 versus 30 min = 42.8 ± 1.4 mg/kg·min, p < 0.05). However, the ability of insulin to stimulate phosphatidylinositol 3,4,5-trisphosphate production and to activate glycogen synthase in skeletal muscle was preserved following up to 180 min of GlcN infusion. Thus, increased GlcN availability induced (a) profound and early inhibition of proximal insulin signaling at the level of PI3K and (b) delayed effects on insulin-mediated glucose uptake, yet (c) complete sparing of insulin-mediated glycogen synthase activation. The pattern and time sequence of GlcN-induced defects suggest that the etiology of peripheral insulin resistance may be distinct from the rapid and marked impairment in insulin signaling.",
author = "Hawkins, {Meredith A.} and Meizhu Hu and Jinghua Yu and Howard Eder and Patricia Vuguin and Li She and Nir Barzilai and Margarita Leiser and Backer, {Jonathan M.} and Luciano Rossetti",
year = "1999",
month = "10",
day = "29",
doi = "10.1074/jbc.274.44.31312",
language = "English (US)",
volume = "274",
pages = "31312--31319",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "44",

}

TY - JOUR

T1 - Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity

AU - Hawkins, Meredith A.

AU - Hu, Meizhu

AU - Yu, Jinghua

AU - Eder, Howard

AU - Vuguin, Patricia

AU - She, Li

AU - Barzilai, Nir

AU - Leiser, Margarita

AU - Backer, Jonathan M.

AU - Rossetti, Luciano

PY - 1999/10/29

Y1 - 1999/10/29

N2 - The impact of increased Glen availability on insulin-stimulated p85/p110 phosphatidylinositol 3-kinase (PI3K) activity in skeletal muscle was examined in relation to GlcN-induced defects in peripheral insulin action. Primed continuous GlcN infusion (750 μmol/kg bolus; 30 μmol/kg·min) in conscious rats limited both maximal stimulation of muscle PI3K by acute insulin (I) (1 unit/kg) bolus (I + GlcN = 1.9-fold versus saline = 3.3-fold above fasting levels; p < 0.01) and chronic activation of PI3K following 3-h euglycemic, hyperinsulinemic (18 milliunits/kg·min) clamp studies (I + GlcN = 1.2-fold versus saline = 2.6-fold stimulation;p < 0.01). To determine the time course of GlcN-induced defects in insulin-stimulated PI3K activity and peripheral insulin action, GlcN was administered for 30, 60, 90, or 120 min during 2-h euglycemic, hyperinsulinemic clamp studies. Activation of muscle PI3K by insulin was attenuated following only 30 rain of GlcN infusion (GlcN 30 min = 1.5-fold versus saline = 2.5-fold stimulation; p < 0.05). In contrast, the first impairment in insulin-mediated glucose uptake (Rd) developed following 110 min of GlcN infusion (110 min = 39.9 ± 1.8 versus 30 min = 42.8 ± 1.4 mg/kg·min, p < 0.05). However, the ability of insulin to stimulate phosphatidylinositol 3,4,5-trisphosphate production and to activate glycogen synthase in skeletal muscle was preserved following up to 180 min of GlcN infusion. Thus, increased GlcN availability induced (a) profound and early inhibition of proximal insulin signaling at the level of PI3K and (b) delayed effects on insulin-mediated glucose uptake, yet (c) complete sparing of insulin-mediated glycogen synthase activation. The pattern and time sequence of GlcN-induced defects suggest that the etiology of peripheral insulin resistance may be distinct from the rapid and marked impairment in insulin signaling.

AB - The impact of increased Glen availability on insulin-stimulated p85/p110 phosphatidylinositol 3-kinase (PI3K) activity in skeletal muscle was examined in relation to GlcN-induced defects in peripheral insulin action. Primed continuous GlcN infusion (750 μmol/kg bolus; 30 μmol/kg·min) in conscious rats limited both maximal stimulation of muscle PI3K by acute insulin (I) (1 unit/kg) bolus (I + GlcN = 1.9-fold versus saline = 3.3-fold above fasting levels; p < 0.01) and chronic activation of PI3K following 3-h euglycemic, hyperinsulinemic (18 milliunits/kg·min) clamp studies (I + GlcN = 1.2-fold versus saline = 2.6-fold stimulation;p < 0.01). To determine the time course of GlcN-induced defects in insulin-stimulated PI3K activity and peripheral insulin action, GlcN was administered for 30, 60, 90, or 120 min during 2-h euglycemic, hyperinsulinemic clamp studies. Activation of muscle PI3K by insulin was attenuated following only 30 rain of GlcN infusion (GlcN 30 min = 1.5-fold versus saline = 2.5-fold stimulation; p < 0.05). In contrast, the first impairment in insulin-mediated glucose uptake (Rd) developed following 110 min of GlcN infusion (110 min = 39.9 ± 1.8 versus 30 min = 42.8 ± 1.4 mg/kg·min, p < 0.05). However, the ability of insulin to stimulate phosphatidylinositol 3,4,5-trisphosphate production and to activate glycogen synthase in skeletal muscle was preserved following up to 180 min of GlcN infusion. Thus, increased GlcN availability induced (a) profound and early inhibition of proximal insulin signaling at the level of PI3K and (b) delayed effects on insulin-mediated glucose uptake, yet (c) complete sparing of insulin-mediated glycogen synthase activation. The pattern and time sequence of GlcN-induced defects suggest that the etiology of peripheral insulin resistance may be distinct from the rapid and marked impairment in insulin signaling.

UR - http://www.scopus.com/inward/record.url?scp=0033615599&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033615599&partnerID=8YFLogxK

U2 - 10.1074/jbc.274.44.31312

DO - 10.1074/jbc.274.44.31312

M3 - Article

C2 - 10531330

AN - SCOPUS:0033615599

VL - 274

SP - 31312

EP - 31319

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 44

ER -