Small intestinal glucose exposure determines the magnitude of the incretin effect in health and type 2 diabetes.
The potential influence of gastric emptying on the "incretin effect," mediated by glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), is unknown. The objectives of this study were to determine the effects of intraduodenal (ID) glucose infusions at 2 (ID2) and 4 (ID4) kcal/min (equating to two rates of gastric emptying within the physiological range) on the size of the incretin effect, gastrointestinal glucose disposal (GIGD), plasma GIP, GLP-1, and glucagon secretion in health and type 2 diabetes. We studied 10 male BMI-matched controls and 11 male type 2 patients managed by diet or metformin only. In both groups, GIP, GLP-1, and the magnitude of incretin effect were greater with ID4 than ID2, as was GIGD; plasma glucagon was suppressed by ID2, but not ID4. There was no difference in the incretin effect between the two groups. Based on these data, we conclude that the rate of small intestinal glucose exposure (i.e., glucose load) is a major determinant of the comparative secretion of GIP and GLP-1, as well as the magnitude of the incretin effect and GIGD in health and type 2 diabetes.
Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
Chinmay S
CS
Marathe
Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
Christopher K
CK
Rayner
Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
Michelle
M
Bound
Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
Helen
H
Checklin
Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
Scott
S
Standfield
Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
Judith
J
Wishart
Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
Kylie
K
Lange
Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
Karen L
KL
Jones
Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia michael.horowitz@adelaide.edu.au.
Michael
M
Horowitz
D000818:Animals; D001786:Blood Glucose; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D054795:Incretins / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male
D001786:Blood Glucose; D002096:C-Peptide; D054795:Incretins; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose