Incretin responses to oral glucose load in Japanese non-obese healthy subjects

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IntroductionRecently, incretin-related therapy has been developed for the new treatment of diabetes mellitus; however, incretin response to glucose ingestion in normal glucose tolerant (NGT) subjects has not been clarified in detail with special reference to the role of incretin hormones, glucagon, and a family history of diabetes.MethodsWe conducted a 75 g oral glucose tolerance test in 30 NGT subjects.ResultsThe total glucose-dependent insulinotropic peptide (GIP)-AUC0–120 (area under the curve over a period of 0–120 minutes) was correlated with immunoreactive insulin (IRI)-AUC0–120 (P<0.05), insulinogenic index (II; P<0.05), ΔIRI between 0 and 120 minutes (P<0.05). Active glucagon-like peptide-1 (GLP-1) AUC0–120 was correlated inversely both with Δ glucose between 0 and 30 minutes (P<0.01) and with Δ immunoreactive glucagon between 0 and 30 minutes (P<0.05). Δ Total GIP between 0 and 15 minutes (P<0.01), Δ total GIP between 0 and 30 minutes (P<0.05), and the total GIP-AUC0–120 (P<0.05) in the subjects with a family history of type 2 diabetes were significantly higher than those in the subjects without a family history.ConclusionThese results suggest that GIP possibly facilitates insulin secretion in response to oral glucose load directly and active GLP-1 may exert the glucoregulatory action via the suppression of glucagon secretion in NGT subjects. Notably, the subjects with a family history of diabetes exert significantly higher GIP response in the early phase of glucose load compared with those without a family history.