GLUT4

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PDB 2al3 EBI

1008 Skeletal Muscle Contraction

Signal Transduction Diagram- Insulin

GLUT4 (Glucose Transporter Type 4) is a protein that in humans is encoded by the SLC2A4 gene. It is a member of the GLUT family of glucose transporters, which facilitate the transport of glucose across the plasma membranes of cells. GLUT4 is particularly important in adipose tissue, skeletal muscle, and the heart, where it is regulated by insulin, making it a critical protein in the process of glucose metabolism and insulin signaling.

Function

GLUT4 is unique among the GLUT family members due to its regulation by insulin. In the absence of insulin, GLUT4 is sequestered in intracellular vesicles in muscle and fat cells. Upon the stimulation of the cells by insulin, these vesicles are translocated to the plasma membrane, where GLUT4 then facilitates the diffusion of glucose into the cells. This process is essential for the maintenance of glucose homeostasis in the body and plays a significant role in the pathophysiology of diabetes mellitus.

Regulation

The translocation of GLUT4 to the plasma membrane is a complex process involving multiple steps and signaling pathways. Insulin binds to its receptor, triggering a cascade that involves the activation of phosphatidylinositol 3-kinase (PI3K) and Akt, leading to the movement of GLUT4-containing vesicles to the cell surface. Additionally, muscle contraction and exercise can also stimulate GLUT4 translocation through insulin-independent mechanisms, highlighting the importance of physical activity in maintaining glucose homeostasis.

Clinical Significance

Given its central role in glucose uptake, GLUT4 is a key player in the development of insulin resistance and type 2 diabetes mellitus. Reduced GLUT4 expression or dysfunction in its insulin-regulated translocation mechanism can lead to decreased glucose uptake by muscle and fat cells, contributing to hyperglycemia and the development of diabetes. Therefore, understanding the regulatory mechanisms controlling GLUT4 translocation and function is crucial for developing therapeutic strategies against diabetes and related metabolic disorders.

Research

Research on GLUT4 includes studies on its structure, the mechanisms regulating its translocation and recycling, and its role in disease states. Animal models, particularly transgenic mice with altered GLUT4 expression, have been instrumental in elucidating the physiological and pathophysiological roles of GLUT4. Ongoing research is focused on identifying novel targets for enhancing GLUT4 activity or expression, with the aim of improving glucose control in diabetic patients.

See Also

• Glucose transporter
• Insulin resistance
• Diabetes mellitus
• Metabolic syndrome