Exogenously imposed postprandial-like rises in systemic glucose and GLP-1 do not produce an incretin effect, suggesting an indirect mechanism of GLP-1 action

• Published in: American journal of physiology: endocrinology and metabolism 2006-10, Vol.291 (4), p.E779-E785
• Main Authors: Ionut, Viorica, Liberty, Idit F, Hucking, Katrin, Lottati, Maya, Stefanovski, Darko, Zheng, Dan, Bergman, Richard N
• Format: Article
• Language: English
• Subjects: Animals; Area Under Curve; C-Reactive Protein - metabolism; Dogs; Eating - physiology; Fatty Acids, Nonesterified - blood; Glucagon - blood; Glucagon-Like Peptide 1 - metabolism; Glucose - metabolism; Insulin - blood; Insulin - metabolism; Insulin-Secreting Cells - metabolism; Male; Postprandial Period; Random Allocation
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00106.2005

Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California Submitted 10 March 2005 ; accepted in final form 16 May 2006 The insulinotropic intestinal hormone GLP-1 is thought to exert one of its effects by direct action on the pancreatic -cell receptors. GLP-1 is rapidly degraded in plasma, such that only a small amount of the active form reaches the pancreas, making it questionable whether this amount is sufficient to produce a direct incretin effect. The aim of our study was to assess, in a dog model, the putative incretin action of GLP-1 acting directly on the -cell in the context of postprandial rises in GLP-1 and glucose. Conscious dogs were fed a high-fat, high-carbohydrate meal, and insulin response was measured. We also infused systemic glucose plus GLP-1, or glucose alone, to simulate the meal test values of these variables and measured insulin response. The results were as follows: during the meal, we measured a robust insulin response (52 ± 9 to 136 ± 14 pmol/l, P < 0.05 vs. basal) with increases in portal glucose and GLP-1 but only limited increases in systemic glucose (5.3 ± 0.1 to 5.7 ± 0.1 mmol/l, P = 0.1 vs. basal) and GLP-1 (6 ± 0 to 9 ± 1 pmol/l, P = 0.5 vs. basal). Exogenous infusion of systemic glucose and GLP-1 produced a moderate increase in insulin (43 ± 5 to 84 ± 15 pmol/l, 43% of the meal insulin). However, infusion of glucose alone, without GLP-1, produced a similar insulin response (37 ± 6 to 82 ± 14 pmol, 53% of the meal insulin, P = 0.7 vs. glucose and GLP-1 infusion). In conclusion, in dogs with postprandial rises in systemic glucose and GLP-1, the hormone might not have a direct insulinotropic effect and could regulate glycemia via indirect, portohepatic-initiated neural mechanisms. glucagon-like peptide-1; insulin secretion; portal; meal test; neural mechanism Address for reprint requests and other correspondence: R. N. Bergman, Keck School of Medicine, Univ. of Southern California, 1333 San Pablo St., Los Angeles CA 90033 (e-mail: rbergman{at}usc.edu )