title: The dipeptidyl peptidase-4 inhibitor vildagliptin has the capacity to repair β-cell dysfunction and insulin resistance.
abstract: The aim of the present study was to determine whether the dipeptidyl peptidase (DPP)-4 inhibitor could repair pancreatic β-cell dysfunction and insulin resistance. Ten subjects with type 2 diabetes who had never received DPP-4 inhibitor treatment were enrolled in the study. Just before and 3 months after twice-daily administration of vildagliptin (50 mg tablets), insulin secretion and insulin sensitivity were estimated using 2-compartment model analysis of C-peptide kinetics and insulin-modified minimal model parameters, respectively. The first-phase insulin secretion (CS1) was determined as the sum of the C-peptide secretion rate (CSR) from 0 to 5 min (normal range 6.8-18.5 ng/ml/min). The whole-body insulin sensitivity index (SI) was calculated using a minimal model software program (normal range 2.6-7.6×10(-4)/min/μU/ml). After vildagliptin treatment, reductions in mean (± SE) HbA1c were noted (43.28±1.53 vs. 40.98±1.77 mmol/mol; p=0.019). Vildagliptin treatment increased the area under the curve for the C peptide reactivity (CPR) (AUCCPR; 26.66±5.15 vs. 33.02±6.12 ng/ml · 20 min; p=0.003) and CS1 (0.80±0.20 vs. 1.35±0.38 ng/ml/min; p=0.037) in response to an intravenous glucose load. -Vildagliptin treatment significantly increased SI (0.46±0.27 vs. 1.21±0.48×10(-4)/min/μU/ml; p=0.037). The long-term administration of vildagliptin improved CS1 and Si suggesting that this drug has the capacity to repair impairments in pancreatic β-cell function and insulin resistance in type 2 diabetes.
authors: The Diabetes Center, Chiba Central Medical Center, Chiba, Japan.
authors: A
authors: A
authors: Horie
authors: Kashiwado Hospital, Chiba, Japan.
authors: Y
authors: Y
authors: Tokuyama
authors: Sato Clinic, Chiba, Japan.
authors: T
authors: T
authors: Ishizuka
authors: Asahi General Hospital, Asahi, Japan.
authors: Y
authors: Y
authors: Suzuki
authors: The Diabetes Center, Chiba Central Medical Center, Chiba, Japan.
authors: K
authors: K
authors: Marumo
authors: The Diabetes Center, Chiba Central Medical Center, Chiba, Japan.
authors: K
authors: K
authors: Oshikiri
authors: The Diabetes Center, Chiba Central Medical Center, Chiba, Japan.
authors: K
authors: K
authors: Ide
authors: The Diabetes Center, Chiba Central Medical Center, Chiba, Japan.
authors: M
authors: M
authors: Sunaga
authors: The Diabetes Center, Chiba Central Medical Center, Chiba, Japan.
authors: A
authors: A
authors: Kanatsuka
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D019540:Area Under Curve; D002097:C-Reactive Protein / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D000077597:Vildagliptin
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; D002097:C-Reactive Protein; D000077597:Vildagliptin; D000218:Adamantane