GLUT4

Glucose transporter type 4, also known as GLUT4, is a protein encoded, in humans, by the GLUT4 gene. GLUT4 is the insulin-regulated glucose transporter found primarily in adipose tissues and striated muscle (skeletal and cardiac). The first evidence for this distinct glucose transport protein was provided by David James in 1988. The gene that encodes GLUT4 was cloned and mapped in 1989.

Recent reports demonstrated the presence of GLUT4 gene in central nervous system such as the hippocampus. Moreover, impairment in insulin-stimulated trafficking of GLUT4 in the hippocampus result in decreased metabolic activities and plasticity of hippocampal neurons, which leads to depressive like behaviour and cognitive dysfunction.

Tissue distribution

GLUT4 is primarily found in:

Regulation

Insulin

Under conditions of low insulin, most GLUT4 is sequestered in intracellular vesicles in muscle and fat cells. Insulin induces a rapid increase in the uptake of glucose by inducing the translocation of GLUT4 from these vesicles to the plasma membrane. As the vesicles fuse with the plasma membrane, GLUT4 transporters are inserted and become available for transporting glucose, and glucose absorption increases. Insulin’s actions are effectively abolished in the genetically engineered muscle insulin receptor knock‐out (MIRKO) mouse because they have a complete lack of the insulin‐sensitive glucose transport protein, GLUT4, in muscle, so insulin has no effect on glucose uptake. Fascinatingly, this is of little or no consequence to the animal that does not have fasting hyperglycaemia or diabetes.