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- Title
Improved Insulin Sensitivity by GLUT12 Overexpression in Mice.
- Authors
Purcell, Scott H.; Aerni-Flessner, Lauren B.; Willcockson, Alexandra R.; Diggs-Andrews, Kelly A.; Fisher, Simon J.; Moley, Kelle H.
- 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 hyperinsulinemiceuglycemic 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. Hyperinsulinemiceuglycemic clamps confirmed enhanced insulin sensitivity in GLUT12-overexpressing mice (P < 0.01). Tissues of TG mice exhibited nomlal 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.
- Subjects
GLUCOSE; BLOOD sugar; INSULIN; MICE; TISSUES; HYPOGLYCEMIC agents
- Publication
Diabetes, 2011, Vol 60, Issue 5, p1478
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db11-0033