TY - JOUR
T1 - Repaglinide acutely amplifies pulsatile insulin secretion by augmentation of burst mass with no effect on burst frequency
AU - Juhl, Claus B.
AU - PØrksen, Niels
AU - Hollingdal, Malene
AU - Sturis, Jeppe
AU - Pincus, Steven
AU - Veldhuis, Johannes D.
AU - Dejgaard, Anders
AU - Schmitz, Ole
PY - 2000
Y1 - 2000
N2 - OBJECTIVE - Repaglinide is a new oral hypoglycemic agent that acts as a prandial glucose regulator proposed for the treatment of type 2 diabetes by stimulating insulin secretion. The aim of this study was to explore actions of repaglinide on the rapid pulsatile insulin release by high-frequency insulin sampling and analysis of insulin-concentration time series. RESEARCH DESIGN AND METHODS - We examined 8 healthy lean male subjects in a single- dose double-blind placebo-controlled crossover design. After the subjects underwent an overnight fast, blood sampling was initiated and continued every minute for 120 min. After 40 min, a single dose (0.5 mg) of repaglinide or placebo was given. Serum insulin-concentration time series were assessed by deconvolution analyses and the regularity statistic by approximate entropy (ApEn). RESULTS - Average insulin concentration was increased after repaglinide administration (basal vs. stimulated period, P values are placebo vs. repaglinide) (25.1 ± 3.6 vs. 33.5 ± 4.1 pmol/l, P < 0.001). Insulin secretory burst mass (15.8 ± 2.2 vs. 19.6 ± 2.8 pmol · 1-1 · pulse - 1, P = 0.02) and amplitude (6.1 ± 0.9 vs. 7.7 ± 1.2 pmol · 1-1 · min -1, p = 0.008) were augmented after repaglinide administration. A concomitant trend toward an increase in basal insulin secretion was observed (2.5 ± 0.3 vs. 3.2 ± 0.4 pmol · l-1 · min-1, P = 0.06), while the interpulse interval was unaltered (6.8 ± 1.0 vs. 5.4 ± 0.4 min/pulse, P = 0.38). ApEn increased significantly after repaglinide administration (0.623 ± 0.045 vs. 0.670 ± 0.034, P = 0.04), suggesting less orderly oscillatory patterns of insulin release. CONCLUSIONS - In conclusion, a single dose of repaglinide amplifies insulin secretory burst mass (and basal secretion) with no change in burst frequency. The possible importance of these mechanisms in the treatment of type 2 diabetes characterized by disrupted pulsatile insulin secretion remains to be clarified.
AB - OBJECTIVE - Repaglinide is a new oral hypoglycemic agent that acts as a prandial glucose regulator proposed for the treatment of type 2 diabetes by stimulating insulin secretion. The aim of this study was to explore actions of repaglinide on the rapid pulsatile insulin release by high-frequency insulin sampling and analysis of insulin-concentration time series. RESEARCH DESIGN AND METHODS - We examined 8 healthy lean male subjects in a single- dose double-blind placebo-controlled crossover design. After the subjects underwent an overnight fast, blood sampling was initiated and continued every minute for 120 min. After 40 min, a single dose (0.5 mg) of repaglinide or placebo was given. Serum insulin-concentration time series were assessed by deconvolution analyses and the regularity statistic by approximate entropy (ApEn). RESULTS - Average insulin concentration was increased after repaglinide administration (basal vs. stimulated period, P values are placebo vs. repaglinide) (25.1 ± 3.6 vs. 33.5 ± 4.1 pmol/l, P < 0.001). Insulin secretory burst mass (15.8 ± 2.2 vs. 19.6 ± 2.8 pmol · 1-1 · pulse - 1, P = 0.02) and amplitude (6.1 ± 0.9 vs. 7.7 ± 1.2 pmol · 1-1 · min -1, p = 0.008) were augmented after repaglinide administration. A concomitant trend toward an increase in basal insulin secretion was observed (2.5 ± 0.3 vs. 3.2 ± 0.4 pmol · l-1 · min-1, P = 0.06), while the interpulse interval was unaltered (6.8 ± 1.0 vs. 5.4 ± 0.4 min/pulse, P = 0.38). ApEn increased significantly after repaglinide administration (0.623 ± 0.045 vs. 0.670 ± 0.034, P = 0.04), suggesting less orderly oscillatory patterns of insulin release. CONCLUSIONS - In conclusion, a single dose of repaglinide amplifies insulin secretory burst mass (and basal secretion) with no change in burst frequency. The possible importance of these mechanisms in the treatment of type 2 diabetes characterized by disrupted pulsatile insulin secretion remains to be clarified.
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U2 - 10.2337/diacare.23.5.675
DO - 10.2337/diacare.23.5.675
M3 - Article
C2 - 10834429
AN - SCOPUS:0034077820
SN - 0149-5992
VL - 23
SP - 675
EP - 681
JO - Diabetes care
JF - Diabetes care
IS - 5
ER -