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Early during the development of type 2 diabetes, insulin's ability to stimulate the cellular uptake of glucose from the blood is compromised. Muscle is the main tissue responsible for this absorption, and insulin enhances glucose movement into muscle cells through the GLUT4 transporter at the cell surface. This hallmark action of insulin is conserved in vertebrates, and the molecular machinery by which it occurs is thought to be similar among mammals. On page 1192 of this issue, Vassilopoulos et al. (4) identify a key protein that mediates insulin action in humans, but not in mice, a distinction with potential implications for understanding glucose metabolism and diabetes pathophysiology.
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