The Dipeptidyl Peptidase IV Inhibitor Vildagliptin Suppresses Endogenous Glucose Production and Enhances Islet Function after Single-Dose Administration in Type 2 Diabetic Patients

Autor: Yan-Ling He, James E. Foley, Jens J. Holst, Andrea Mari, Bogdan Balas, Ralph A. DeFronzo, Muhammad R. Baig, Catherine Watson, Celia Darland, Beth E. Dunning, Carolyn F. Deacon, Monica Ligueros-Saylan, Kenneth Cusi, Yibin Wang
Rok vydání: 2007
Předmět:
Male
medicine.medical_specialty
Pyrrolidines
Adenosine Deaminase
Dipeptidyl Peptidase 4
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Clinical Biochemistry
Adamantane
Type 2 diabetes
Biology
Biochemistry
Dipeptidyl peptidase
Body Mass Index
Islets of Langerhans
Endocrinology
Double-Blind Method
Diabetes mellitus
Internal medicine
Nitriles
Adenosine Deaminase Inhibitors
medicine
Humans
Hypoglycemic Agents
Vildagliptin
Obesity
Enzyme Inhibitors
Glycoproteins
Glycated Hemoglobin
Dipeptidyl-Peptidase IV Inhibitors
geography
Cross-Over Studies
geography.geographical_feature_category
Insulin
digestive
oral
and skin physiology
Biochemistry (medical)
Middle Aged
medicine.disease
Islet
Glucagon-like peptide-1
Kinetics
Glucose
Postprandial
Diabetes Mellitus
Type 2
Female
medicine.drug
Zdroj: The Journal of Clinical Endocrinology & Metabolism. 92:1249-1255
ISSN: 1945-7197
0021-972X
DOI: 10.1210/jc.2006-1882
Popis: Vildagliptin is a selective dipeptidyl peptidase IV inhibitor that augments meal-stimulated levels of biologically active glucagon-like peptide-1. Chronic vildagliptin treatment decreases postprandial glucose levels and reduces hemoglobin A1c in type 2 diabetic patients. However, little is known about the mechanism(s) by which vildagliptin promotes reduction in plasma glucose concentration.Sixteen patients with type 2 diabetes (age, 48+/-3 yr; body mass index, 34.4+/-1.7 kg/m2; hemoglobin A1c, 9.0+/-0.3%) participated in a randomized, double-blind, placebo-controlled trial. On separate days patients received 100 mg vildagliptin or placebo at 1730 h followed 30 min later by a meal tolerance test (MTT) performed with double tracer technique (3-(3)H-glucose iv and 1-(14)C-glucose orally).After vildagliptin, suppression of endogenous glucose production (EGP) during 6-h MTT was greater than with placebo (1.02+/-0.06 vs. 0.74+/-0.06 mg.kg-1.min-1; P=0.004), and insulin secretion rate increased by 21% (P=0.003) despite significant reduction in mean plasma glucose (213+/-4 vs. 230+/-4 mg/dl; P=0.006). Consequently, insulin secretion rate (area under the curve) divided by plasma glucose (area under the curve) increased by 29% (P=0.01). Suppression of plasma glucagon during MTT was 5-fold greater with vildagliptin (P0.02). The decline in EGP was positively correlated (r=0.55; P0.03) with the decrease in fasting plasma glucose (change=-14 mg/dl).During MTT, vildagliptin augments insulin secretion and inhibits glucagon release, leading to enhanced suppression of EGP. During the postprandial period, a single dose of vildagliptin reduced plasma glucose levels by enhancing suppression of EGP.
Databáze: OpenAIRE
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