title: Improved insulin sensitivity by GLUT12 overexpression in mice.
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.
  
  
  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 [(3)H]-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.
authors: Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri, USA.
authors: Scott H
authors: SH
authors: Purcell
authors: Lauren B
authors: LB
authors: Aerni-Flessner
authors: Alexandra R
authors: AR
authors: Willcockson
authors: Kelly A
authors: KA
authors: Diggs-Andrews
authors: Simon J
authors: SJ
authors: Fisher
authors: Kelle H
authors: KH
authors: Moley
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000097:blood*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D000199:Actins; D001786:Blood Glucose; D051246:Glucose Transport Proteins, Facilitative; D007328:Insulin; C498337:Slc2a12 protein, mouse