Xie, C.Huang, W.Watson, L.E.Soenen, S.Young, R.L.Jones, K.L.Horowitz, M.Rayner, C.K.Wu, T.2022-01-112022-01-112022Journal of Clinical Endocrinology and Metabolism (JCEM), 2022; 107(4):e1643-e16520021-972X1945-7197https://hdl.handle.net/2440/134031First Published Online: 13 November 2021Context 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.en© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.gastric emptying; GLP-1; postprandial glucose metabolism; type 2 diabetesJournal article10.1210/clinem/dgab8282022-01-11594511Xie, C. [0000-0002-0054-9269]Huang, W. [0000-0001-9400-3840]Soenen, S. [0000-0002-0196-128X]Young, R.L. [0000-0001-5116-4951] [0009-0004-8274-9863]Jones, K.L. [0000-0002-1155-5816]Horowitz, M. [0000-0002-0942-0306]Rayner, C.K. [0000-0002-5527-256X]Wu, T. [0000-0003-1656-9210]