Fiber type-specific determinants of Vmax for insulin-stimulated muscle glucose uptake in vivo

Hilary Ann Petersen, Patrick T. Fueger, Deanna P. Bracy, David H. Wasserman, Amy E. Halseth

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Abstract

The aim of this study was to determine barriers limiting muscle glucose uptake (MGU) during increased glucose flux created by raising blood glucose in the presence of fixed insulin. The determinants of the maximal velocity (Vmax) of MGU in muscles of different fiber types were defined. Conscious rats were studied during a 4 mU·kg-1·min-1 insulin clamp with plasma glucose at 2.5, 5.5, and 8.5 mM. [U-14C] mannitol and 3-O-methyl-[3H]glucose ([3H]MG) were infused to steady-state levels (t = - 180 to 0 min). These isotope infusions were continued from 0 to 40 min with the addition of a 2-deoxy-[3H] glucose ([3H]DG) infusion. Muscles were excised at t = 40 min. Glucose metabolic index (Rg) was calculated from muscle-phosphorylated [3H] DG. [U-14C] mannitol was used to determine extracellular (EC) H2O. Glucose at the outer ([G]om) and inner ([G]im) sarcolemmal surfaces was determined by the ratio of [3H] MG in intracellular to EC H2O and muscle glucose. Rg was comparable at the two higher glucose concentrations, suggesting that rates of uptake near Vmax were reached. In summary, by defining the relationship of arterial glucose to [G]om and [G]im in the presence of fixed hyperinsulinemia, it is concluded that 1) Vmax for MGU is limited by extracellular and intracellular barriers in type I fibers, as the sarcolemma is freely permeable to glucose; 2) Vmax is limited in muscles with predominantly type IIb fibers by extracellular resistance and transport resistance; and 3) limits to Rg are determined by resistance at multiple steps and are better defined by distributed control rather than by a single rate-limiting step.

Original languageEnglish (US)
Pages (from-to)E541-E548
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume284
Issue number3 47-3
StatePublished - Mar 1 2003

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Keywords

  • Extracellular, intracellular water
  • Glucose analogs
  • Rat

ASJC Scopus subject areas

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

Cite this

Petersen, H. A., Fueger, P. T., Bracy, D. P., Wasserman, D. H., & Halseth, A. E. (2003). Fiber type-specific determinants of Vmax for insulin-stimulated muscle glucose uptake in vivo. American Journal of Physiology - Endocrinology and Metabolism, 284(3 47-3), E541-E548.