Plasma GLP-1 response to oral and intraduodenal nutrients in health and type 2 diabetes - impact on gastric emptying

Date

2022

Authors

Xie, C.
Huang, W.
Watson, L.E.
Soenen, S.
Young, R.L.
Jones, K.L.
Horowitz, M.
Rayner, C.K.
Wu, T.

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Journal article

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Journal of Clinical Endocrinology and Metabolism (JCEM), 2022; 107(4):e1643-e1652

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Cong Xie, Weikun Huang, Linda E Watson, Stijn Soenen, Richard L Young, Karen L Jones, Michael Horowitz, Christopher K. Rayner, and Tongzhi Wu

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Abstract

Context Both gastric emptying and the secretion of glucagon-like peptide-1 (GLP-1) are major determinants of postprandial glycemia in health and type 2 diabetes (T2D). GLP-1 secretion after a meal is dependent on the entry of nutrients into the small intestine, which, in turn, slows gastric emptying. Objective To define the relationship between gastric emptying and the GLP-1 response to both oral and small intestinal nutrients in subjects with and without T2D. Methods We evaluated: (i) the relationship between gastric emptying (breath test) and postprandial GLP-1 levels after a mashed potato meal in 73 individuals with T2D; (ii) inter-individual variations in GLP-1 response to (a) intraduodenal glucose (4 kcal/min) during euglycemia and hyperglycemia in 11 healthy and 12 T2D, subjects, (b) intraduodenal fat (2 kcal/min) in 15 T2D subjects, and (c) intraduodenal protein (3 kcal/min) in 10 healthy subjects; and (iii) the relationship between gastric emptying (breath test) of 75 g oral glucose and the GLP-1 response to intraduodenal glucose (4 kcal/min) in 21 subjects (9 healthy, 12 T2D). Results The GLP-1 response to the mashed potato meal was unrelated to the gastric half-emptying time (T50). The GLP-1 responses to intraduodenal glucose, fat, and protein varied substantially between individuals, but intra-individual variation to glucose was modest. The T50 of oral glucose was related directly to the GLP-1 response to intraduodenal glucose (r = 0.65, P = 0.002). Conclusion In a given individual, gastric emptying is not a determinant of the postprandial GLP-1 response. However, the intrinsic gastric emptying rate is determined in part by the responsiveness of GLP-1 to intestinal nutrients.

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First Published Online: 13 November 2021

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© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.

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