Insulin, Muscle Glucose Uptake, and Hexokinase: Revisiting the Road Not Taken

Research conducted over the last 50 years has provided insight into the mechanisms by which insulin stimulates glucose transport across the skeletal muscle cell membrane. Transport alone, however, does not result in net glucose uptake as freeglucose equilibrates across the cell membrane and is not metabolized. Glucose uptake requires that glucose is phosphorylated by hexokinases. Phosphorylated glucosecannot leave the cell and is the substrate for metabolism. It is indisputable that glucose phosphorylation is essential for glucose uptake. Major advances have been made in defining the regulation of the insulin-stimulated glucose transporter, GLUT4, in skeletalmuscle. By contrast, the insulin-regulated hexokinase, hexokinase II parallels RobertFrost's Road Not Taken. Here the case is made that an understanding of glucosephosphorylation by hexokinase II is necessary to define the regulation of skeletal muscle glucose uptake in health and insulin resistance. Results of studies from different physiological disciplines that have elegantly described how hexokinase II can beregulated are summarized to provide a framework for potential application to skeletal muscle. Mechanisms by which hexokinase II is regulated in skeletal muscle await rigorous examination.

Peptide/Cas9 nanostructures for ribonucleoprotein cell membrane transport and gene edition

The hydrazone modulation of a penetrating peptide carrier is reported as a suitable and straightforward strategy for the delivery of Cas9 inside living cells.