Improved Insulin Sensitivity by GLUT12 Overexpression in Mice

  1. Kelle H. Moley1
  1. 1Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri
  2. 2Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri
  1. Corresponding author: Kelle H. Moley, moleyk{at}wustl.edu.

Abstract

OBJECTIVE 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.

RESEARCH DESIGN AND METHODS 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.

RESULTS 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.

CONCLUSIONS 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.

Footnotes

  • Received January 11, 2011.
  • Accepted February 26, 2011.

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  1. Diabetes vol. 60 no. 5 1478-1482
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