We quantified the contribution of GLP-1 as a mediator of the therapeutic effects of dipeptidyl peptidase 4 (DPP-4) inhibition (vildagliptin) by using the GLP-1 receptor antagonist exendin in patients with type 2 diabetes and in healthy subjects. Thirty-two patients with type 2 diabetes and 29 age-and weight-matched healthy control subjects were treated in randomized order with 100 mg once daily vildagliptin or placebo for 10 days. Meal tests were performed (days 9 and 10) without and with a high-dose intravenous infusion of exendin . The main end point was the ratio of the areas under the curve (AUCs) of integrated insulin secretion rates (total AUC ISR ) and glucose (total AUC glucose ) over 4 h after the meal. Vildagliptin treatment more than doubled responses of intact GLP-1 and glucose-dependent insulinotropic polypeptide and lowered glucose responses without changing AUC ISR /AUC glucose in healthy subjects. Vildagliptin significantly increased this ratio by 10.5% in patients with type 2 diabetes, and exendin [9-39] reduced it (both P < 0.0001). The percentage reduction in the AUC ISR / AUC glucose ratio achieved with exendin [9-39] was significantly smaller after vildagliptin treatment than after placebo treatment (P = 0.026) and was equivalent to 47 6 5% of the increments due to vildagliptin. Thus, other mediators appear to contribute significantly to the therapeutic effects of DPP-4 inhibition.

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The CI2Se-N-SeCl2+ cation which represents the first example of a ternary Se, N, CI species has been prepared by the reaction of SeCI3+AsF6-and N(SiMe3)3; the crystal structure of the AsF6-salt has been determined b y a low-temperature single crystal X-ray diffraction study.

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