A Serum Factor Induces Insulin-Independent Translocation of GLUT4 to the Cell Surface which Is Maintained in Insulin Resistance

In response to insulin, glucose transporter GLUT4 translocates from intracellular compartments towards the plasma membrane where it enhances cellular glucose uptake. Here, we show that sera from various species contain a factor that dose-dependently induces GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes, human adipocytes, myoblasts and myotubes. Notably, the effect of this factor on GLUT4 is fully maintained in insulin-resistant cells. Our studies demonstrate that the serum-induced increase in cell surface GLUT4 levels is not due to inhibition of its internalization and is not mediated by insulin, PDGF, IGF-1, or HGF. Similarly to insulin, serum also augments cell surface levels of GLUT1 and TfR. Remarkably, the acute effect of serum on GLUT4 is largely additive to that of insulin, while it also sensitizes the cells to insulin. In accordance with these findings, serum does not appear to activate the same repertoire of downstream signaling molecules that are implicated in insulin-induced GLUT4 translocation. We conclude that in addition to insulin, at least one other biological proteinaceous factor exists that contributes to GLUT4 regulation and still functions in insulin resistance. The challenge now is to identify this factor

The janus faces of botulinum neurotoxin: Sensational medicine and deadly biological weapon

The botulinum neurotoxins are the most dangerous toxins known (BoNTs serotypes A-G) and induce profound flaccid neuromuscular paralysis by blocking nerve-muscle communication. Poisoned motoneurons react by emitting a sprouting network known to establish novel functional synapses with the abutting muscle fiber. Understanding how our motoneurons are capable of bypassing such transmission blockade, thereby overcoming paralysis, by an astonishing display of plasticity is one of the research goals that have numerous therapeutic ramifications. This Review aims at giving a brief update on the recent discoveries regarding the molecular mechanism of botulinum toxins intoxication. Curing botulism still is a challenge once the toxin has found his way inside motoneurons. In view of the potential use of botulinum toxins as biological weapon, more research is needed to find efficient ways of curing this disease. (C) 2007 Wiley-Liss, Inc