Accurate measurement of endogenous insulin secretion does not require separate assessment of C-peptide kinetics.

Abstract

The implication of -cell failure as an early defect in t y p e 2 diabetes exacerbates the need for accurate but facile assessment of islet cell secretory rate, particularly in large group studies in which individual assessment of C-peptide kinetics is impractical. This study was designed to examine whether it is possible to obtain accurate secretory rates from the extended combined model, which provides insulin and C-peptide kinetics from plasma measurements of the two peptides. Equimolar intraportal infusions of insulin and C-peptide that are designed to simulate insulin secretion rates during both oral and intravenous glucose tolerance tests were used to generate plasma insulin and C-peptide data in conscious dogs that were examined under clamped glucose conditions. The plasma peptide kinetics were analyzed using the extended combined model to generate estimates of prehepatic insulin secretion that were then compared with the known intraportal infusion rates. The extended combined model was able to reproduce the known intraportal infusion profiles. The model-predicted rates were similar to those calculated with methods that require separate assessment of C-peptide kinetics. Simulation results supported lesser clearance of insulin during rapid changes of portal insulin (as measured by an intravenous glucose tolerance test) versus slow changes in portal insulin (as measured by an oral glucose tolerance test). The extended combined model accurately calculates prehepatic insulin appearance. It may be possible to apply this approach to large studies of -cell function designed to identify changes in islet function in subjects at risk for diabetes. Such an approach could strengthen epidemiological and genetic studies of the pathogenesis of diabetes. D i a b e t e s 4 9 :3 7 3-382, 2000

Reduced insulin clearance contributes to the increased insulin levels after administration of glucagon-like peptide 1 in mice

“…We found that the variations in the parameters of C-peptide kinetics within our animal population were small: for example, V tot changed little and body weight had no influence in spite of the large variation among animals. Another aspect that made us confident about the correctness of our approach was that C-peptide kinetics, estimated in mice, was comparable to that previously reported in humans [20] and dogs [21]: therefore, it can be considered a valid basis for reconstructing prehepatic insulin secretion by deconvolution of C-peptide measurements.…”

Synergistic effect of portal glucose and glucagon-like peptide-1 to lower systemic glucose and stimulate counter-regulatory hormones

“…Insulin secretion was calculated from the C-peptide data using the deconvolution analysis based on a two-compartment model of C-peptide kinetics, as previously described [23].…”

Quantification of beta-cell function during IVGTT in Type II and non-diabetic subjects: assessment of insulin secretion by mathematical methods

“…These include the Eaton deconvolution method [15,16], the Insulin SECretion method (ISEC) [17±19] and the combined model with one-compartment [23,24] or two-compartments for C-peptide kinetics [25,26] (see Methods). The deconvolution technique has been used in many physiological and pathological conditions [5, 7, 10, 15, 16, 28±30] and has been simplified by using populationbased kinetic parameters of C-peptide instead of individually determined parameters [17].…”

“…This model has later been modified to encompass two-compartment C-peptide kinetics [25,26]. We have recently assessed the accuracy of the original deconvolution method and the combined model during slow changes in insulin appearance rates, as seen during an oral glucose tolerance test [31].…”