BACKGROUND/AIMS: Chronic amylase inhibition might be useful to treat diabetes mellitus and obesity. Duodenal and ileal cannulas were placed in 8 dogs to determine if long-term ingestion of a wheat amylase inhibitor maintained amylase inhibition or affected gastrointestinal or metabolic function or pancreatic growth. METHODS: Five dogs were fed and 3 were not fed 1.5 g of the inhibitor with meals for 9 weeks. Postprandial and cholecystokinin octapeptide stimulated pancreatic secretion, and fecal balance studies were performed at intervals. After the experiment, the pancreas was analyzed. RESULTS: Weight loss was similar in both groups. Amylase inhibition persisted throughout the 9 weeks; it declined from 91% to 37% from the first to the sixth postprandial hour. Amylase inhibition decreased plasma glucose levels during the first hour (P < 0.05), increased carbohydrate delivery to the ileum (315 vs. 555 mg/h; P = 0.002), and increased cholecystokinin octapeptide-stimulated amylase secretion. However, amylase inhibition did not significantly change plasma concentrations of insulin, peptide YY or neurotensin, postprandial pancreatic secretion, gastrointestinal transit or pancreatic weight, and protein or DNA content. CONCLUSIONS: Prandial ingestion of 1.5 g of the inhibitor for 9 weeks reduces postprandial amylase levels enough to delay carbohydrate digestion and absorption and lower plasma glucose levels without altering pancreatic growth. This dose may be effective to treat diabetes mellitus but not obesity.
BACKGROUND/AIMS: Chronic amylase inhibition might be useful to treat diabetes mellitus and obesity. Duodenal and ileal cannulas were placed in 8 dogs to determine if long-term ingestion of a wheat amylase inhibitor maintained amylase inhibition or affected gastrointestinal or metabolic function or pancreatic growth. METHODS: Five dogs were fed and 3 were not fed 1.5 g of the inhibitor with meals for 9 weeks. Postprandial and cholecystokinin octapeptide stimulated pancreatic secretion, and fecal balance studies were performed at intervals. After the experiment, the pancreas was analyzed. RESULTS:Weight loss was similar in both groups. Amylase inhibition persisted throughout the 9 weeks; it declined from 91% to 37% from the first to the sixth postprandial hour. Amylase inhibition decreased plasma glucose levels during the first hour (P < 0.05), increased carbohydrate delivery to the ileum (315 vs. 555 mg/h; P = 0.002), and increased cholecystokinin octapeptide-stimulated amylase secretion. However, amylase inhibition did not significantly change plasma concentrations of insulin, peptide YY or neurotensin, postprandial pancreatic secretion, gastrointestinal transit or pancreatic weight, and protein or DNA content. CONCLUSIONS: Prandial ingestion of 1.5 g of the inhibitor for 9 weeks reduces postprandial amylase levels enough to delay carbohydrate digestion and absorption and lower plasma glucose levels without altering pancreatic growth. This dose may be effective to treat diabetes mellitus but not obesity.