First Author | Purcell SH | Year | 2011 |
Journal | Diabetes | Volume | 60 |
Issue | 5 | Pages | 1478-82 |
PubMed ID | 21441439 | Mgi Jnum | J:171745 |
Mgi Id | MGI:4999661 | Doi | 10.2337/db11-0033 |
Citation | Purcell SH, et al. (2011) Improved Insulin Sensitivity by GLUT12 Overexpression in Mice. Diabetes 60(5):1478-82 |
abstractText | 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 beta-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. |