title: 13C/31P NMR studies on the mechanism of insulin resistance in obesity.
abstract: The mechanism of insulin resistance in obesity was examined in ten obese (BMI 33 +/- 1 kg/m2) and nine lean (BMI 22 +/- 1 kg/m2) Caucasian women during a hyperglycemic-hyperinsulinemic clamp using 13C and 31P nuclear magnetic resonance (NMR) spectroscopy to measure rates of muscle glycogen synthesis and intramuscular glucose-6-phosphate (G-6-P) concentrations. Under similar steady-state plasma concentrations of glucose (approximately 11 mmol/l) and insulin (approximately 340 pmol/l), rates of muscle glycogen synthesis were reduced approximately 70% in the obese subjects (52 +/- 8 micromol/[l muscle-min]) as compared with the rates in the lean subjects (176 +/- 22 micromol/[l muscle-min]; P < 0.0001). Basal concentrations of intramuscular G-6-P were similar in the obese and lean subjects; but during the clamp, G-6-P failed to increase in the obese group (deltaG-6-P obese 0.044 +/- 0.011 vs. lean 0.117 +/- 0.011 mmol/l muscle; P < 0.001), reflecting decreased muscle glucose transport and/or phosphorylation activity. We conclude that insulin resistance in obesity can be mostly attributed to impairment of insulin-stimulated muscle glycogen synthesis due to a defect in glucose transport and/or phosphorylation activity.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA. kitt.petersen@yale.edu
authors.forename: K F
authors.initials: KF
authors.lastname: Petersen
authors.forename: R
authors.initials: R
authors.lastname: Hendler
authors.forename: T
authors.initials: T
authors.lastname: Price
authors.forename: G
authors.initials: G
authors.lastname: Perseghin
authors.forename: D L
authors.initials: DL
authors.lastname: Rothman
authors.forename: N
authors.initials: N
authors.lastname: Held
authors.forename: J M
authors.initials: JM
authors.lastname: Amatruda
authors.forename: G I
authors.initials: GI
authors.lastname: Shulman
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D009765:Obesity / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D044465:White People
chemical_list: D006003:Glycogen; D005947:Glucose