title: Novel antidiabetic nutrients identified by in vivo screening for gastric secretion and emptying regulation in rats.
abstract: 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.
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; and Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Josua
authors.initials: J
authors.lastname: Jordi
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland; Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Herzog
authors.affiliation: Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; and Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Lutz
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland; Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland verrey@access.uzh.ch.
authors.forename: François
authors.initials: F
authors.lastname: Verrey
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D005502:Food; D005746:Gastric Emptying / Q000502:physiology*; D005934:Glucagon / Q000097:blood; D006943:Hyperglycemia / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D008297:Male; D019518:Postprandial Period / Q000502:physiology; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005934:Glucagon
keywords: computed tomography; diabetes; exenatide; liraglutide; postprandial hyperglycemia; pramlintide