No abstract

Pancreatic enzyme supplementation plays an important role in incretin secretion, gastric emptying, and postprandial hyperglycemia in CF.

The short-acting glucagon-like peptide 1 receptor agonist exenatide reduces postprandial glycemia, partly by slowing gastric emptying, although its impact on small intestinal function is unknown. In this study, 10 healthy subjects and 10 patients with type 2 diabetes received intravenous exenatide (7.5 mg) or saline (230 to 240 min) in a double-blind randomized crossover design. Glucose (45 g), together with 5 g 3-O-methylglucose (3-OMG) and 20 MBq 99m Tc-sulfur colloid (total volume 200 mL), was given intraduodenally (t = 0-60 min; 3 kcal/min). Duodenal motility and flow were measured using a combined manometry-impedance catheter and small intestinal transit using scintigraphy. In both groups, duodenal pressure waves and antegrade flow events were fewer, and transit was slower with exenatide, as were the areas under the curves for serum 3-OMG and blood glucose concentrations. Insulin concentrations were initially lower with exenatide than with saline and subsequently higher. Nausea was greater in both groups with exenatide, but suppression of small intestinal motility and flow was observed even in subjects with little or no nausea. The inhibition of small intestinal motor function represents a novel mechanism by which exenatide can attenuate postprandial glycemia.Therapies specifically targeting postprandial glycemia are important in the management of type 2 diabetes, especially in patients with relatively good overall glycemic control (HbA 1c #7.5%; 58 mmol/mol) (1). The rate of gastric emptying is an established determinant of postprandial blood glucose (2), a principle illustrated by "short-acting" glucagonlike peptide 1 (GLP-1) receptor agonists, such as exenatide, where the capacity to slow gastric emptying predominates over the insulinotropic effect in the postprandial setting (3).Small intestinal glucose absorption, predominantly via sodium-glucose cotransporter 1 and GLUT2 transporters, is limited to ;0.5 g/min per 30 cm (2). Interventions that increase the exposure of luminal glucose to the mucosal surface can therefore augment glucose absorption. We previously reported that the anticholinergic agent hyoscine delays the absorption of intraduodenally infused glucose in humans by decreasing small intestinal flow (4), indicating PHARMACOLOGY AND THERAPEUTICSthat modulation of small intestinal motor function can impact substantially on postprandial glycemia. Exogenous GLP-1 has been reported to inhibit both fasting and postprandial duodenal motility in humans (5,6), but its impact on the flow of chyme and on small intestinal transit and glucose absorption have not previously been explored. We therefore examined the effects of the short-acting form of exenatide on small intestinal motor function and glucose absorption in response to an intraduodenal glucose infusion in both healthy subjects and patients with type 2 diabetes. RESEARCH DESIGN AND METHODS SubjectsWe studied 10 healthy subjects and 10 patients with type 2 diabetes managed by diet alone, after obtaining written informed consent (Table 1). None ...