Normal muscle glucose uptake in mice deficient in muscle GLUT4

J Endocrinol. 2012 Sep;214(3):313-27. doi: 10.1530/JOE-12-0032. Epub 2012 Jun 26.


Skeletal muscle insulin resistance is a major characteristic underpinning type 2 diabetes. Impairments in the insulin responsiveness of the glucose transporter, Glut4 (Slc2a4), have been suggested to be a contributing factor to this disturbance. We have produced muscle-specific Glut4 knockout (KO) mice using Cre/LoxP technology on a C57BL6/J background and shown undetectable levels of GLUT4 in both skeletal muscle and heart. Our aim was to determine whether complete deletion of muscle GLUT4 does in fact lead to perturbations in glucose homoeostasis. Glucose tolerance, glucose turnover and 2-deoxyglucose uptake into muscle and fat under basal and insulin-stimulated conditions were assessed in 12-week-old KO and control mice using the oral glucose tolerance test (OGTT) and hyperinsulinaemic/euglycaemic clamp respectively. KO mice weighed ~17% less and had significantly heavier hearts compared with control mice. Basally, plasma glucose and plasma insulin were significantly lower in the KO compared with control mice, which conferred normal glucose tolerance. Despite the lack of GLUT4 in the KO mouse muscle, glucose uptake was not impaired in skeletal muscle but was reduced in heart under insulin-stimulated conditions. Neither GLUT1 nor GLUT12 protein levels were altered in the skeletal muscle or heart tissue of our KO mice. High-fat feeding did not alter glucose tolerance in the KO mice but led to elevated plasma insulin levels during the glucose tolerance test. Our study demonstrates that deletion of muscle GLUT4 does not adversely affect glucose disposal and glucose tolerance and that compensation from other transporters may contribute to this unaltered homoeostasis of glucose.

MeSH terms

  • Animals
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Dietary Fats / pharmacology
  • Female
  • Genes, Homeobox / physiology
  • Glucose Clamp Technique
  • Glucose Intolerance / genetics
  • Glucose Intolerance / metabolism
  • Glucose Tolerance Test
  • Glucose Transport Proteins, Facilitative / genetics
  • Glucose Transport Proteins, Facilitative / metabolism
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism
  • Glucose Transporter Type 4 / genetics*
  • Glucose Transporter Type 4 / metabolism*
  • Integrases / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / metabolism*
  • Pregnancy
  • RNA, Messenger / metabolism


  • Blood Glucose
  • Dietary Fats
  • Glucose Transport Proteins, Facilitative
  • Glucose Transporter Type 1
  • Glucose Transporter Type 4
  • RNA, Messenger
  • Slc2a1 protein, mouse
  • Slc2a12 protein, mouse
  • Slc2a4 protein, mouse
  • Cre recombinase
  • Integrases