Individual differences in cephalic-phase insulin response are stable over time and predict glucose tolerance in mice.

Oral stimulation by glucose triggers a rapid insulin response, which enhances glucose tolerance. This so-called cephalic-phase insulin response (CPIR) has been documented in many mammal species, but its functional properties are poorly characterized. Here, we studied CPIR in lean C57BL/6 mice. Experiment 1 asked whether the large individual differences in CPIR magnitude were real or reflected experimental noise. We measured CPIR magnitude four times across a period of 30 days in the same mice. The individual differences in CPIR magnitude were remarkably stable across the repeated trials, indicating that they were real. Experiment 2 examined the functional consequences of individual differences in CPIR magnitude. We found that higher CPIR magnitudes contributed to larger postprandial insulin responses and greater glucose tolerance. Experiment 3 examined the observation that the CPIRs in Experiments 1 and 2 were associated with a rapid rise in blood glucose. To determine whether the rapid rise in blood glucose caused the CPIRs, we asked whether mice would generate a CPIR if we prevented cephalic-phase stimulation of beta cells by either delivering the glucose intragastrically or blocking parasympathetic input to the pancreatic beta cells with atropine. The mice subjected to these treatments experienced a rapid rise in blood glucose, but they did not exhibit a CPIR. This indicates that it was the oral glucose stimulation, and not the rise in blood glucose, that triggered the CPIRs in Experiments 1 and 2. We conclude that (i) individual differences in CPIR magnitude are stable over time; (ii) CPIR magnitudes predicted postprandial insulin responses and glucose tolerance; and (iii) a rapid rise in blood glucose is not sufficient to trigger a CPIR in mice.