We also based our decision on a recent report showing PF-6463922 order that 3.42 g GS-9973 price leucine alone, in the absence of carbohydrate

intake and at rest, increased plasma insulin concentration by 50% within 30 min before returning to basal levels [23]. It is thus possible that the smaller amount of leucine, compared to previous studies, added to the high amount of glucose (~1 g/kg/h) was not large enough to further enhance plasma insulin concentration in the present study. Based on our data, 1000 mg OFI had a slightly higher insulinogenic action than 3 g leucine, certainly 30 min after ingestion of the glucose + OFI beverage. OFI seems to stimulate insulin production acutely and rapidly as serum insulin concentrations GF120918 clinical trial during the OGTT each time were increased 30 min after OFI ingestion but no more 60 min after OFI intake. The insulinogenic action of OFI thus clearly is short-lived. The largest effect on plasma insulin concentration was obtained by the combined ingestion of OFI plus leucine. Indeed, insulin concentration was persistently elevated during the second hour of the OGTT when OFI and leucine were administered together. In addition, a trend (P=0.09) to increase in insulin concentration was observed in OFI + LEU compared with OFI alone at 60 and 120 min. As

blood glucose concentrations were not modified by OFI plus leucine, the increase in insulin did not result from higher blood glucose levels. Our results rather indicate

that OFI and leucine directly stimulate pancreatic insulin release, and that the effects of both agents are additive. Whereas the physiological mechanism by which OFI facilitates glucose-induced pancreatic insulin release remains to be elucidated, it is known that leucine increases pancreatic β-cell insulin secretion through: 1) its oxidative decarboxylation; 2) its ability to allosterically activate glutamate dehydrogenase, and 3) its transamination to α-ketoisocaproate [24]. Those events will subsequently lead to an increased tricarboxylic acid-cycle flux, an increased ATP/ADP ratio, the closure of the ATP-sensitive potassium channels, a depolarization of the plasma membrane and the opening of the calcium sensitive channels which will finally cause the secretion of insulin [25–27]. Whether OFI increases the tricarboxylic acid-cycle many flux in beta-cells as well, or whether it depolarizes the membrane via a different mechanism than leucine remains to be investigated. The combination of OFI with leucine seems the best option to increase plasma insulin concentrations after exercise and thereby to potentially accelerate glycogen resynthesis. Nevertheless we did not measure any difference in the area under the glucose curve when both treatments were given together compared to placebo, which could indicate that muscle glucose uptake probably is not substantially modified by combined OFI plus leucine administration.