NDLI: Restoration of the insulinotropic effect of glucose-dependent insulinotropic polypeptide contributes to the antidiabetic effect of dipeptidyl peptidase-4 inhibitors.

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Restoration of the insulinotropic effect of glucose-dependent insulinotropic polypeptide contributes to the antidiabetic effect of dipeptidyl peptidase-4 inhibitors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Aaboe, K. Akram, S. Deacon, C. F. Holst, J. J. Madsbad, S. Krarup, T.
Description	Country affiliation: Denmark Author Affiliation: Aaboe K ( Department of Endocrinology I, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.)
Abstract	AIMS: To examine whether 12 weeks of treatment with a dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin, influences the insulin secretion induced by glucose, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) during a hyperglycaemic clamp in patients with type 2 diabetes (T2DM). METHODS: A randomized, double-blind, placebo-controlled study was conducted over 12 weeks, during which 25 patients with T2DM completed treatment with either sitagliptin (100 mg once daily) or placebo as add-on therapy to metformin [sitagliptin group (n = 12): mean ± standard error of the mean (s.e.m.) age 54 ± 2.5 years, mean ± s.e.m. HbA1c 7.8 ± 0.2%; placebo group (n = 13): mean ± s.e.m. age: 57 ± 3.0 years, mean ± s.e.m. HbA1c 7.9 ± 0.2 %]. In weeks 1 and 12, the patients underwent three 2-h 15-mM hyperglycaemic clamp experiments with infusion of either saline, GLP-1 or GIP. ß-cell function was evaluated according to first-phase, second-phase, incremental and total insulin and C-peptide responses. RESULTS: In the sitagliptin group, the mean HbA1c concentration was significantly reduced by 0.9% (p = 0.01). The total ß-cell response during GIP infusion improved significantly from week 1 to week 12, both within the sitagliptin group (p = 0.004) and when compared with the placebo group (p = 0.04). The total ß-cell response during GLP-1 infusion was significantly higher (p = 0.001) when compared with saline and GIP infusion, but with no improvement from week 1 to week 12. No significant changes in ß-cell function occurred in the placebo group. CONCLUSIONS: Treatment with the DPP-4 inhibitor sitagliptin over 12 weeks in patients with T2DM partially restored the lost insulinotropic effect of GIP, whereas the preserved insulinotropic effect of GLP-1 was not further improved. A gradual enhancement of the insulinotropic effect of GIP, therefore, possibly contributes to the antidiabetic actions of DPP-4 inhibitors.
File Format	HTM / HTML
ISSN	14628902
Issue Number	1
Volume Number	17
e-ISSN	14631326
Journal	Diabetes, Obesity and Metabolism
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2015-01-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Metabolism Discipline Endocrinology Discipline Pharmacology Discipline Diabetology Diabetes Mellitus, Type 2 Drug Therapy Dipeptidyl-peptidase Iv Inhibitors Therapeutic Use Gastric Inhibitory Polypeptide Metabolism Insulin-secreting Cells Drug Effects Insulin Secretion Pyrazines Triazoles Up-regulation C-peptide Blood Adverse Effects Double-blind Method Drug Therapy, Combination Female Glucagon-like Peptide 1 Glucose Clamp Technique Hemoglobin A, Glycosylated Analysis Humans Hyperglycemia Prevention & Control Hypoglycemic Agents Male Metformin Middle Aged Sitagliptin Phosphate Comparative Study Journal Article Randomized Controlled Trial Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Endocrinology, Diabetes and Metabolism Internal Medicine Endocrinology

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Restoration of the insulinotropic effect of glucose-dependent insulinotropic polypeptide contributes to the antidiabetic effect of dipeptidyl peptidase-4 inhibitors.

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Restoration of the insulinotropic effect of glucose-dependent insulinotropic polypeptide contributes to the antidiabetic effect of dipeptidyl peptidase-4 inhibitors.