Transgenic mice expressing the human GLUT4/muscle-fat facilitative glucose transporter protein exhibit efficient glycemic control

Min Ling Liu, E. Michael Gibbs, Scott C. Mccoid, A. J. Milici, Hans A. Stukenbrok, R. Kirk Mcpherson, Judith L. Treadway, Jeffrey E. Pessin

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Abstract

To examine the physiological role of the GLUT4/muscle-fat specific facultative glucose transporter in regulating glucose homeostasis, we have generated transgenic mice expressing high levels of this protein in an appropriate tissue-specific manner. Examination of two independent founder lines demonstrated that high-level expression of GLUT4 protein resulted in a marked reduction of fasting glucose levels (≈70 mg/dl) compared to wild-type mice (≈130 mg/dl). Surprisingly, 30 min following an oral glucose challenge the GLUT4 transgenic mice had only a slight elevation in plasma glucose levels (≈90 mg/dl), whereas wild-type mice displayed a typical 2- to 3-fold increase (≈250-300 mg/dl). In parallel to the changes in plasma glucose, insulin levels were ≈2 -fold lower in the transgenic mice compared to the wild-type mice. Furthermore, isolated adipocytes from the GLUT4 transgenic mice had increased basal glucose uptake and subcellular fractionation indicated elevated levels of cell surface-associated GLUT4 protein. Consistent with these results, in situ immunocytochemical localization of GLUT4 protein in adipocytes and cardiac myocytes indicated a marked increase in plasma membrane-associated GLUT4 protein in the basal state. Taken together these data demonstrate that increased expression of the human GLUT4 gene in vivo results in a constitutively high level of cell surface GLUT4 protein expression and more efficient metabolic control over fluctuations in plasma glucose concentrations.

Original languageEnglish (US)
Pages (from-to)11346-11350
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number23
DOIs
StatePublished - Dec 1 1993

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