There is controversy over whether glucagon-like peptide (GLP-1) has effects on peripheral glucose uptake which can be attributed to GLP-1 per se (i.e., separate from its insulinotrophic effects). Furthermore, there may be an organ specific differential effect between GLP-1 and GLP-1amide.
The aim of this study is to first examine the effect of GLP-1 influsion during a period of maintained euglycemia on glucose uptake and hepatic glucose production (HGP). In the second study, which will be repeated at least htree weeks after the first study, volunteers will receive an influsion of insulin in a manner which results in plasma insulin profile nearly identical to those induced by the infusion of GLP-1. If GLP-1 does indeed have insulin-like effects separate from hyperinsulinemia with respect to glucose metabolized (M), then M in the first study should be greater than M in the second study. If this is true, then a third study will be performed where the insulin dose will be increased in order to produce an equivalent glucose utilization to that obtained in the first study. This will quantify the extent of GLP-1's insulin-like effect with respect to glucose uptake per se. If M is not different between study 1 and 2 with the use of GLP-1, GLP-1 will be infused to test whether organ- specific receptor differences are present in the liver and the muscle bed. It has been shown that there are no insulinotrophic differences between these two peptides in humans. However, there is controversy whether or not GLP-1 has any insulin-like effects on glucose uptake and production in the muscle and liver.
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