Diabetes mellitus is a disease characterized by elevated
blood glucose levels and represents a worldwide health issue.
Postprandial hyperglycemia is considered a major predictor of
diabetic complications, and its reduction represents a specific treatment target in Type 1 and 2 diabetes. Since postprandial
glucose excursions depend to a large extent on gastric secretion and emptying,
amylin and
glucagon-like peptide 1 analogs are prescribed to reduce them. Although gastric function is considered mainly sensitive to ingested calories, its chemospecificity is not well understood. To identify ingestible nutrients reducing
postprandial hyperglycemia, we applied intragastrically more than 40 individual nutrients at an
isomolar dose to rats and quantified their impact on gastric secretion and emptying using a novel in vivo computed tomography imaging method. We identified
l-tryptophan,
l-arginine,
l-cysteine, and
l-lysine as the most potent modulators with effective strength comparable to a supraphysiological dose of
amylin. Importantly, all identified candidates reduced postprandial
glucose excursion within an oral
glucose tolerance test in healthy and diabetic rats. This clinical beneficial effect originated predominantly from their impact on gastric function, as none of the candidates altered plasma
glucose concentrations induced by intraperitoneal or intraduodenal
glucose tolerance tests. Overall, these data demonstrate a remarkable chemospecificity of stomach function, unveil a strong role of the stomach for
glycemic control and identifies nutrients with
antidiabetic potential.