Dose-responsive Insulin Regulation of Glucose Transport in Human Skeletal Muscle.
From: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
American journal of physiology. Endocrinology and metabolism
- Publish Date: Jun 2006
- ISSN: 0193-1849
- Volume: 290
- Issue: 6
- Pages: E1124-30
- Medium: Print
- Language: English
- Citation (JAMA): Pencek R Richard, Bertoldo Alessandra, Price Julie, et al. Dose-responsive Insulin Regulation of Glucose Transport in Human Skeletal Muscle.. Am. J. Physiol. Endocrinol. Metab. Jun 2006;290:E1124-30
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.
Mesh Headings (Keywords): Biological Transport, Blood Glucose, Dose-Response Relationship, Drug, Fatty Acids, Nonesterified, Glucose Clamp Technique, Guanosine, Humans, Insulin, Magnetic Resonance Imaging, Muscle, Skeletal, Positron-Emission Tomography, Time Factors
Check for Full Text / PubMed Unique Identifier (PMID): 16390860
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