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Dipeptidyl Peptidase-4 Inhibition by Vildagliptin and the Effect on Insulin Secretion and Action in Response to Meal Ingestion in Type 2 Diabetes
Oleh:
Man, Chiara Dalla
;
Bock, Gerlies
;
Giesler, Paula D.
;
Serra, Denise B.
;
Saylan, Monica Ligueros
Jenis:
Article from Journal - ilmiah internasional
Dalam koleksi:
Diabetes Care vol. 32 no. 01 (Jan. 2009)
,
page 14-18.
Topik:
Dipeptidyl Peptidase-4 Inhibition Meal Ingestion
Ketersediaan
Perpustakaan FK
Nomor Panggil:
D05.K.2009.01
Non-tandon:
1 (dapat dipinjam: 0)
Tandon:
tidak ada
Lihat Detail Induk
Isi artikel
OBJECTIVE—The purpose of this study was to determine the mechanism by which dipeptidyl peptidase-4 inhibitors lower postprandial glucose concentrations. RESEARCH DESIGN AND METHODS—We measured insulin secretion and action as well as glucose effectiveness in 14 subjects with type 2 diabetes who received vildagliptin (50 mg b.i.d.) or placebo for 10 days in random order separated by a 3-week washout. On day 9 of each period, subjects ate a mixed meal. Insulin sensitivity (SI), glucose effectiveness, and ß-cell responsivity indexes were estimated using the oral glucose and C-peptide minimal models. At 300 min 0.02 unit/kg insulin was administered intravenously. RESULTS—Vildagliptin reduced postprandial glucose concentrations (905 ± 94 vs. 1,008 ± 104 mmol/6 h, P = 0.02). Vildagliptin did not alter net SI (7.71 ± 1.28 vs. 6.41 ± 0.84 10-4 dl · kg-1 · min-1 · µU-1 · ml-1, P = 0.13) or glucose effectiveness (0.019 ± 0.002 vs. 0.018 ± 0.002 dl · kg-1 · min-1, P = 0.65). However, the net ß-cell responsivity index was increased (35.7 ± 5.2 vs. 28.9 ± 5.2 10-9 min-1, P = 0.03) as was total disposition index (381 ± 48 vs. 261 ± 35 10-14 dl · kg-1 · min-2 · pmol-1 · l-1, P = 0.006). Vildagliptin lowered postprandial glucagon concentrations (27.0 ± 1.1 vs. 29.7 ± 1.5 µg · l-1 · 6 h-1, P = 0.03), especially after administration of exogenous insulin (81.5 ± 6.4 vs. 99.3 ± 5.6 ng/l, P = 0.02). CONCLUSIONS—Vildagliptin lowers postprandial glucose concentrations by stimulating insulin secretion and suppressing glucagon secretion but not by altered insulin action or glucose effectiveness. A novel observation is that vildagliptin alters a-cell responsiveness to insulin administration, but the significance of this action is as yet unclear.
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