Beta-Cells Secrete Two
Hormones for a Good Reason

To continue our “outside the box” model building, we now ask a teleological question: why would beta-cells make two hormones, given that one hormone would be the more energy efficient way for beta-cells to exert their glucoregulatory authority?  In this regard we quote William of Ockham: “Pluralitas non est ponenda sine neccesitate” or “Entities should not be multiplied unnecessarily.”  As we pointed out in Part 1, an amidated peptide hormone is an energy hill that Mother Nature doesn’t want to climb without good reason.

In other words, why couldn’t circulating insulin serve as the neuroendocrine message from beta-cells to the central nervous system?  Beta-cell secretion of insulin has already been proposed as the alpha-cell inhibitor that controls glucagon secretion, and this “insulin switch-off model” necessarily assumes insulin’s secretion profile is appropriate for alpha-cell suppression.  Couldn’t the CNS cells which respond to circulating plasma amylin instead detect plasma insulin, since plasma insulin levels rise at mealtimes when slowing of gastric emptying and suppression of glucagon secretion are needed?  And, the hypoglycemia circuit-breaker could work just as well with insulin as the beta-cell signal to the CNS.

We believe the most plausible rationale for the second beta-cell hormone is that the diurnal plasma profile of insulin is not appropriate for regulation of blood glucose influx from the gut and liver.  Insulin secretion is tightly correlated with circulating glucose and is aimed at controlling blood glucose efflux into liver, muscle, and fat tissues at mealtimes.  If the diurnal profile that optimizes blood glucose efflux is different from the optimal influx profile, then a single hormone could not properly regulate both efflux and influx.

To test this theory, we start by asking: do the physiologies of insulin and amylin predict differences in circulating profiles?