GLUT4aktivitet

GLUT4 activity refers to the regulation and translocation of the GLUT4 glucose transporter, mainly in adipose tissue and skeletal muscle. GLUT4 is stored in intracellular vesicles and moves to the plasma membrane in response to stimuli such as insulin and muscle contraction, thereby increasing glucose uptake into cells. In German- and Scandinavian-language literature, the term GLUT4aktivität is used to describe this process.

Insulin-stimulated GLUT4 translocation involves a signaling cascade beginning with the insulin receptor and IRS proteins, leading to PI3K activation and production of PIP3. This activates Akt, particularly Akt2, which then phosphorylates AS160/TBC1D4 and TBC1D1. Phosphorylation relieves their inhibition of Rab GTPases, promoting movement of GLUT4 storage vesicles toward the plasma membrane and their docking and fusion via SNARE proteins such as syntaxin-4, SNAP23, and VAMP2.

Exercise-induced GLUT4 translocation provides an insulin-independent pathway to increase glucose uptake. Muscle contraction activates AMPK and calcium-dependent signaling, which also promotes GLUT4 vesicle trafficking to the cell surface, enabling rapid glucose disposal during and after activity.

Physiological relevance and regulation: GLUT4 activity is a major determinant of insulin-stimulated glucose uptake and overall glucose homeostasis. In obesity and insulin resistance, GLUT4 translocation and/or expression can be impaired, contributing to hyperglycemia. Interventions like endurance and resistance training or weight loss can improve GLUT4 translocation and insulin sensitivity.

Genetics and measurement: Variants in SLC2A4 are rare but may affect transporter expression or trafficking. GLUT4 activity is typically assessed indirectly via glucose uptake assays or imaging of GLUT4 localization in cells and tissues.