Relationship between carnitine, fatty acids and insulin resistance.

Increased plasma free fatty acid (FFA) levels are a feature of insulin resistance and type 2 diabetes. The aim of the present study was to assess the effect of L-carnitine supplementation on plasma lipids and the expression of enzymes in peripheral mononucleated cells (PMNC) involved in the regulation of fatty acid and glucose oxidation. L-Carnitine supplementation of 2 g/day resulted in a significant decrease in plasma FFA and in a less pronounced diminution of the plasma triacylglycerols. In addition, a concomitant increase in the relative mRNA abundances of carnitine acyltransferases (5- to 10-fold) and of the carnitine carrier OCTN2 (12-fold) in PMNC of pregnant women was found. The results of the present study provide evidence that L-carnitine supplementation in pregnancy (2 g/day) avoids a striking increase in plasma FFA, which are thought to be the main cause of insulin resistance and consequently gestational diabetes mellitus.

Design of supported membranes tethered via metal-affinity ligand-receptor pairs.

Model lipid layers are very promising in investigating the complex network of recognition, transport and signaling processes at membranes. We have developed a novel and generic approach to create supported lipid membranes tethered by metal-affinity binding. By self-assembly we have generated various interfaces that display histidine sequences (6xHis) via polymer spacers. These histidine-functionalized interfaces are designed to allow specific docking and fusion of vesicles containing metal-chelating lipids. By means of surface plasmon resonance and atomic force microscopy we analyzed the formation and subsequently the structure of these solid-supported membranes. Although the affinity constant of single ligand-receptor pairs is only in the micromolar range, very stable immobilization of these membranes was observed. This behavior can be explained by multivalent interactions resembling many features of cell adhesion. The process is highly specific, because vesicle docking and bilayer formation are strictly dependent on the presence of metal-affinity ligand-receptor pairs. The surface accessibility and geometry of these tethered membranes were probed by binding of histidine-tagged polypeptides. The supported membranes show adsorption kinetics and values similar to planar supported monolayers. Using various combinations of metal-chelating and histidine-tagged lipids or thiols these metal-affinity-tethered membranes should make a great impact on probing and eventually understanding the dynamic dialog of reconstituted membrane proteins.