title: Dose-responsive insulin regulation of glucose transport in human skeletal muscle.
abstract: Glucose transport is regarded as the principal rate control step governing insulin-stimulated glucose utilization by skeletal muscle. To assess this step in human skeletal muscle, quantitative PET imaging of skeletal muscle was performed using 3-O-methyl-[11C]glucose (3-[11C]OMG) in healthy volunteers during a two-step insulin infusion [n = 8; 30 and 120 mU.min(-1).m(-2), low (LO) and high (HI)] and during basal conditions (n = 8). Positron emission tomography images were coregistered with MRI to assess 3-[11C]OMG activity in regions of interest placed on oxidative (soleus) compared with glycolytic (tibialis anterior) muscle. Insulin dose-responsive increases of 3-[11C]OMG activity in muscle were observed (P < 0.01). Tissue activity was greater in soleus than in tibialis anterior (P < 0.05). Spectral analysis identified that two mathematical components interacted to shape tissue activity curves. These two components were interpreted physiologically as likely representing the kinetics of 3-[11C]OMG delivery from plasma to tissue and the kinetics of bidirectional glucose transport. During low compared with basal, there was a sixfold increase in k3, the rate constant attributed to inward glucose transport, and another threefold increase during HI (0.012 +/- 0.003, 0.070 +/- 0.014, 0.272 +/- 0.059 min(-1), P < 0.001). Values for k3 were similar in soleus and tibialis anterior, suggesting similar kinetics for transport, but compartmental modeling indicated a higher value in soleus for k1, denoting higher rates of 3-[11C]OMG delivery to soleus than to tibialis anterior. In summary, in healthy volunteers there is robust dose-responsive insulin stimulation of glucose transport in skeletal muscle.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: R Richard
authors.initials: RR
authors.lastname: Pencek
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bertoldo
authors.forename: Julie
authors.initials: J
authors.lastname: Price
authors.forename: Carol
authors.initials: C
authors.lastname: Kelley
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.forename: David E
authors.initials: DE
authors.lastname: Kelley
mesh_terms: D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D006151:Guanosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood*; D008279:Magnetic Resonance Imaging; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D049268:Positron-Emission Tomography; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; C037626:3'-O-methylguanosine; D006151:Guanosine