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: A Horie, Y Tokuyama, T Ishizuka, Y Suzuki, K Marumo, K Oshikiri, K Ide, M Sunaga, A Kanatsuka
• Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme (Horm Metab Res) Vol. 46 Issue 11 Pg. 814-8 (Oct 2014) ISSN: 1439-4286 [Electronic] Germany
• PMID: 24977657 (Publication Type: Journal Article)
• Copyright: © Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Insulin
• Nitriles
• Pyrrolidines
• C-Reactive Protein
• Vildagliptin
• Adamantane

Topics

• Adamantane (analogs & derivatives, pharmacology)
• Area Under Curve
• C-Reactive Protein (metabolism)
• Dipeptidyl-Peptidase IV Inhibitors (pharmacology)
• Fasting
• Female
• Glucose Tolerance Test
• Humans
• Insulin (metabolism)
• Insulin Resistance
• Insulin Secretion
• Insulin-Secreting Cells (drug effects, pathology)
• Male
• Middle Aged
• Nitriles (pharmacology)
• Pyrrolidines (pharmacology)
• Vildagliptin