Quantitative indexes of beta-cell function during graded up&down glucose infusion from C-peptide minimal models

Availability of quantitative indexes of insulin secretion is important for definition of the alterations in beta -cell responsivity to glucose associa ted with different physiopathological states. This is presently possible by using the intravenous glucose tolerance test (IVGTT) in conjunction with t he C-peptide minimal model. However, the secretory response to a more physi ological slowly increasing/decreasing glucose stimulus may uncover novel fe atures of beta -cell function. Therefore, plasma C-peptide and glucose data from a graded glucose infusion protocol (seven 40-min periods of 0, 4, 8, 16, 8, 4, and 0 mg.kg(-1).min(-1)) in eight normal subjects were analyzed b y use of a new model of insulin secretion and kinetics. The model assumes a two-compartment description of C-peptide kinetics and describes the stimul atory effect on insulin secretion of both glucose concentration and the rat e at which glucose increases. It provides in each individual the insulin se cretion profile and three indexes of pancreatic sensitivity to glucose: Phi (s), Phi (d), and Phi (b), related, respectively, to the control of insuli n secretion by the glucose level (static control), the rate at which glucos e increases (dynamic control), and basal glucose. Indexes (means +/- SE) we re Phi (s) = 18.8 +/- 1.8 (10(9) min(-1)), Phi (d) = 222 +/- 30 (10(9)), an d Phi (b) = 5.2 +/- 0.4 (10(9) min(-1)). The model also allows one to quant ify the beta -cell times of response to increasing and decreasing glucose s timulus, equal to 5.7 +/- 2.2 (min) and 17.8 +/- 2.0 (min), respectively. I n conclusion, the graded glucose infusion protocol, interpreted with a mini mal model of C-peptide secretion and kinetics, provides a quantitative asse ssment of pancreatic function in an individual. Its application to various physiopathological states should provide novel insights into the role of in sulin secretion in the development of glucose intolerance.