Plasma GLP-1 Response to Oral and Intraduodenal Nutrients in Health and Type 2 Diabetes—Impact on Gastric Emptying

Author:

Xie Cong1,Huang Weikun1,Watson Linda E1,Soenen Stijn12,Young Richard L13ORCID,Jones Karen L14,Horowitz Michael14ORCID,Rayner Christopher K15,Wu Tongzhi14ORCID

Affiliation:

1. Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, SA 5000, Australia

2. Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, QLD 4226, Australia

3. Nutrition, Diabetes & Gut Health, Lifelong Health Theme, South Australian Health & Medical Research Institute, Adelaide, SA 5000, Australia

4. Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia

5. Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia

Abstract

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.

Funder

China Scholarship Council

William T Southcott Research Fellowship

Hospital Research Foundation

National Health and Medical Research Council

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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