Improved Insulin Sensitivity by GLUT12 Overexpression in Mice
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- Scott H. Purcell
- Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri
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- Lauren B. Aerni-Flessner
- Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri
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- Alexandra R. Willcockson
- Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri
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- Kelly A. Diggs-Andrews
- Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri
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- Simon J. Fisher
- Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri
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- Kelle H. Moley
- Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri
Abstract
<jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>Evidence suggests that insulin-sensitive glucose transporters (GLUTs) other than GLUT4 may exist. To investigate whether GLUT12 may represent another insulin-sensitive GLUT, transgenic (TG) mice that overexpress GLUT12 were characterized.</jats:p> </jats:sec> <jats:sec> <jats:title>RESEARCH DESIGN AND METHODS</jats:title> <jats:p>TG mice that overexpressed GLUT12 under a β-actin promoter were generated. Glucose metabolism in TG and wild-type control mice was compared using glucose and insulin tolerance tests and hyperinsulinemic-euglycemic clamps. In addition, basal and insulin-stimulated glucose clearance rates into insulin-sensitive peripheral tissues were measured using [3H]-2-deoxy-d-glucose.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>GLUT12 was overexpressed by 40–75% in TG compared with wild-type mice in insulin-sensitive tissues with no change in GLUT4 content. Body weight and fasting blood glucose did not differ between wild-type and TG mice; however, insulin concentrations were reduced in TG mice. Enhanced oral glucose tolerance was noted in TG mice by a reduced blood glucose excursion compared with wild-type mice (P < 0.05). Enhanced insulin sensitivity was noted by a greater decrease in blood glucose in TG mice during insulin tolerance testing. Hyperinsulinemic-euglycemic clamps confirmed enhanced insulin sensitivity in GLUT12-overexpressing mice (P < 0.01). Tissues of TG mice exhibited normal basal glucose clearance rates; however, under insulin-stimulated conditions, glucose clearance was significantly increased (P < 0.01) in tissues of TG mice.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>Increased expression of GLUT12 results in improved whole-body insulin sensitivity mediated by an increased glucose clearance rate in insulin-responsive tissues under insulin-stimulated, but not basal, conditions. These findings provide evidence that GLUT12 represents a novel, second insulin-sensitive GLUT.</jats:p> </jats:sec>
Journal
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- Diabetes
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Diabetes 60 (5), 1478-1482, 2011-04-23
American Diabetes Association
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Details 詳細情報について
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- CRID
- 1361699996116424960
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- ISSN
- 1939327X
- 00121797
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- Data Source
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- Crossref