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Novel antidiabetic nutrients identified by in vivo screening for gastric secretion and emptying regulation in rats


Jordi, Josua; Herzog, Brigitte; Lutz, Thomas A; Verrey, François (2014). Novel antidiabetic nutrients identified by in vivo screening for gastric secretion and emptying regulation in rats. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 307(7):R869-R878.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:1 October 2014
Deposited On:16 Oct 2014 18:36
Last Modified:05 Apr 2016 18:25
Publisher:American Physiological Society
ISSN:0363-6119
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1152/ajpregu.00273.2014
PubMed ID:25100072
Permanent URL: https://doi.org/10.5167/uzh-99533

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