OBJECTIVE: A mechanistic, physiologically-based pharmacokinetic (PK/PD) model was developed to describe the biphasic insulin release and evaluate the racial effects on the glucose-insulin kinetics in response to intravenous glucose. METHODS: Fifteen African-American and 18 Caucasian children and adolescents between 8 and 18 years of age were enrolled in the study. Intravenous bolus of glucose (250 mg/kg) was administered and blood samples collected at frequent intervals for three hours following the glucose injection. A nonlinear mixed-effect population kinetic analysis with covariate structure was performed using Monolix. RESULTS: A significantly higher initial insulin secretion from a readily releasable pool, which is responsible for the first-phase insulin secretion, was detected in African-Americans compared to Caucasians (p<0.05). CONCLUSIONS: The proposed kinetic model is able to describe the glucose-stimulated insulin response, account for the first-phase insulin release and identify a racially-based pharmacokinetic difference in insulin's biphasic secretion behavior. It is hypothesized that the first-phase insulin component may play an important role in the development of type 2 diabetes. The proposed mechanistic model provides a quantitative analysis of the biphasic insulin release that may be useful in the early detection of diabetes. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
OBJECTIVE: A mechanistic, physiologically-based pharmacokinetic (PK/PD) model was developed to describe the biphasic insulin release and evaluate the racial effects on the glucose-insulin kinetics in response to intravenous glucose. METHODS: Fifteen African-American and 18 Caucasian children and adolescents between 8 and 18 years of age were enrolled in the study. Intravenous bolus of glucose (250 mg/kg) was administered and blood samples collected at frequent intervals for three hours following the glucose injection. A nonlinear mixed-effect population kinetic analysis with covariate structure was performed using Monolix. RESULTS: A significantly higher initial insulin secretion from a readily releasable pool, which is responsible for the first-phase insulin secretion, was detected in African-Americans compared to Caucasians (p<0.05). CONCLUSIONS: The proposed kinetic model is able to describe the glucose-stimulated insulin response, account for the first-phase insulin release and identify a racially-based pharmacokinetic difference in insulin's biphasic secretion behavior. It is hypothesized that the first-phase insulin component may play an important role in the development of type 2 diabetes. The proposed mechanistic model provides a quantitative analysis of the biphasic insulin release that may be useful in the early detection of diabetes. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
Authors: Claus Juhl; Thorbjørn Grøfte; Peter C Butler; Johannes D Veldhuis; Ole Schmitz; Niels Pørksen Journal: Diabetes Date: 2002-02 Impact factor: 9.461
Authors: S Lillioja; D M Mott; M Spraul; R Ferraro; J E Foley; E Ravussin; W C Knowler; P H Bennett; C Bogardus Journal: N Engl J Med Date: 1993-12-30 Impact factor: 91.245