Use of c-peptide as a measure of cephalic phase insulin release in humans

Abstract

AbstractCephalic phase insulin release (CPIR) is a rapid pulse of insulin secreted within minutes of food-related sensory stimulation. Understanding the mechanisms underlying CPIR in humans has been hindered by its small observed effect size and high variability within and between studies. One contributing factor to these limitations may be the use of peripherally measured insulin as an indicator of secreted insulin, since a substantial portion of insulin is metabolized by the liver before delivery to peripheral circulation. Here, we investigated the use of c-peptide, which is co-secreted in equimolar amounts to insulin from pancreatic beta cells, as a proxy for insulin secretion during the cephalic phase period. Changes in insulin and c-peptide were monitored in 18 adults over two repeated sessions following oral stimulation with a sucrose-containing gelatin stimulus. We found that on average, insulin and c-peptide release followed a similar time course over the cephalic phase period, but that c-peptide showed a greater effect size. Importantly, when insulin and c-peptide concentrations were compared across sessions, we found that changes in c-peptide were significantly correlated at the 2 minute (r = 0.50, p = 0.03) and 4 minute (r = 0.65, p = 0.003) time points, as well as when individuals’ peak c-peptide concentrations were considered (r = 0.64, p = 0.004). In contrast, no significant correlations were observed for changes in insulin measured from the sessions (r = −0.06-0.35, p < 0.05). Herein, we detail the individual variability of insulin and c-peptide release during the cephalic phase period, and discuss why c-peptide may be a more appropriate metric to represent insulin secretion.