Regional glucose infusion on gut function

Following an overnight fast, each subject will receive the following four treatments, separated by at least 7 days: (1) intraduodenal (ID) glucose infusion at a rate of 2 kcal/min (2) IV glucose infusion at a variable rate designed to match the blood glucose profile of the ID study day (ie. an isoglycaemic infusion) (3) intraileal (II) glucose infusion at a rate of 2 kcal/min (4) IV isoglycaemic infusion to match the blood glucose profile of the II study day The order of ID and II infusion is randomised, while each IV isoglycaemic infusion is administered following ID or ID infusion. ID or II infusion days: For ID infusion, the catheter will be positioned with the infusion port located 10 cm distal to the pylorus. For II infusion, the infusion port will be positioned 200 cm distal to the pylorus. Once the intraluminal catheter is correctly positioned, 30 g glucose (together with 3 g 3-O-methylglucose (3-OMG) for assessment of glucose absorption), dissolved in water to a total volume of 120 mL, will be infused into the duodenum or mid-ileum for 60 min (t = 0 – 60 min, ie. 2 kcal/min). At the end of infusion (t = 60 min), the catheter will be removed. “Arterialised” blood samples (10 mL) will be sampled at t = 0, 15, 30, 45, 60, 90, 120, 150 and 180 min. At t = 180 min, each subject will be given a meal and monitored to ensure stable blood glucose concentrations over the next 60 min, after which they will be allowed to leave the laboratory. IV “isoglycaemic” infusion days: An IV cannula will be placed in a forearm vein for IV administration of 25% glucose to mimic the glycaemic excursions on the preceding ID or II glucose infusion study visit. The infusion will be guided by recording blood glucose every 5 minutes and adjusting infusion rate accordingly (Medisense Precision QID, Abbott Laboratories, Bedford, MA, USA). “Arterialised” blood samples (10 mL) will be also be sampled at t = 0, 15, 30, 45, 60, 90, 120, 150 and 180 min for subsequent measurement of plasma concentrations of GLP-1, GIP, insulin, C-peptide and glucagon. At t = 180 min, each subject will be given a meal and monitored to ensure stable blood glucose concentrations over the next 60 min, after which they will be allowed to leave the laboratory.