Energy regulation in humans is controlled through complicated mechanisms involving among others hormones secreted from different tissues, such as gut, muscle and adipose tissue. Specifically, the hormonal secretion after nutrient intake mediates the metabolic response in order to maintain energy balance. Proglucagon-derived hormones and especially GLP-1 and glucagon are significantly affected by nutrient intake and by energy balance. Despite the extensive information about GLP-1 and glucagon, it remains unclear whether other proglucagon-derived hormones are regulated by nutrition or by energy status i.e. obesity or type 2 diabetes. Similarly, secretion of activins and follistatins, which are both affecting muscle metabolism-growth and consequently energy homeostasis, are reduced in energy deprivation states. However, we do not know whether the circulating profile of these hormones is affected acutely by nutrient intake and whether these changes have acute effects on muscle metabolism. We propose to conduct a non-blinded interventional study evaluating the effects of oral or intravenous glucose intake in the circulating levels of proglucagon-derived hormones, activin A, activin B, follistatin, follistatin-like 3.

Screening Visit: Potential subjects will present for a study screening visit in the study site. A written informed consent will be obtained by a study physician at the screening visit. Potential subjects will have their medical history obtained and will be examined by a study physician. Vitals will be taken and height, weight, and waist circumference will be measured. Potential subjects will have a screening fingerstick glucose test as a marker of diabetes and blood collected for CBC and basic lipid panel. Menstrual status will be assessed by menstrual history (female subjects only) and women will take a urine pregnancy test and will be excluded from participation if pregnant. Subjects will meet with a registered dietitian. Visit 1: Subjects will return to the GCRC after a 10-hour overnight fast. In the study site, subjects will have vital signs and anthropometrics measured. All subjects will have one IV line, used to obtain blood samples for insulin, glucose, proglucagon derived hormones and muscle-acting hormones (activin A, activin B, follistatin, follistatin-like 3). Participants will consume orally glucose 1.25 grams/kg in 200 ml water at time 0 and the same amount again at 3 hours. During the 6-hour period they are also going to receive normal saline (NaCL 0,9%) at a rate of 0.83 plus Heparin, 800 IU/h with a priming dose of 1000 IU. Blood collection will be obtained from the IV line at 30 min intervals for the first 2 hrs and hourly thereafter. Visit 2: Subjects will return after a 10-hour overnight visit. Visit 2 will be performed at least 1 week after Visit 1. All subjects will have two IV lines, one for obtaining blood samples for insulin, glucose, proglucagon derived hormones and muscle-acting hormones (activin A, activin B, follistatin, follistatin-like 3) and another one for the intravenous administration of glucose. Specifically a 10% intravenous glucose infusion at a rate of 3.6 ml/kg/h plus Heparin 800 IU/h with a priming dose of 1000 IU will be administrated for 6 hours. At time 0 and at 3 hours they will drink 300 ml water to control for any effects of gastric distension. Blood collection will be obtained from the IV line at 30 min intervals for the first 2 hrs and hourly thereafter. Each blood draw will be 15 ml (5 ml in EDTA tubes with aprotinin and 10 ml in serum tubes).