Population correlations do not support the existence of set points for blood levels of calcium or glucose - a new model for homeostasis.

Stephen P Fitzgerald,Nigel G Bean

doi:10.14814/phy2.13551

Abstract

The prevailing teaching regarding homeostasis, and in particular endocrine homeostasis, includes the fundamental concept of a “set point,” which represents a target or optimum level defended by physiological control mechanisms. Analogies for the description and teaching of this concept have included thermostats and cruise controls. We previously demonstrated that such a set‐point model of regulation implies that in population data of parameter set point/controlling hormone levels, correlations between the parameter and its controlling hormone must be in the direction of the response of the parameter to its controlling hormone, and that in thyroid homeostasis this relationship is not observed. In this work we similarly examined population correlations, extracted from the literature, for the parameters glucose and calcium, and their controlling hormones. We found 10 correlations. Most were highly significant (P < 0.01). All were in the direction of the response of the controlling hormone to the parameter. Therefore, none were consistent with the pattern implied by a set‐point model of regulation. Instead all were consistent with an “equilibrium point” model of regulation, whereby ambient levels have no particular connotation to the individual, and result passively from the interplay of physiological processes. We conclude that glucose and calcium regulation, like thyroid regulation, are not centered on set points. This may reflect a general property of homeostasis. We provide an alternative mechanistic analogy, without a set point, for the heuristic description and teaching, of homeostasis.

Highlights

We studied the regulation of glucose/insulin, and calcium/parathyroid hormone (PTH), so as to determine whether or not the nature of thyroid regulation is typical of regulation in endocrinology and homeostasis in general
We have extended our findings with regard to thyroid homeostasis to calcium and glucose homeostasis
We have shown that in both of these systems, all the population correlations are in the opposite direction to those of the relationship describing the effect of the controlling hormone on the parameter of interest

Summary

Introduction

“Homeostasis” is believed to be one of eight core concepts in biology and one of the two “big ideas” (concepts) in physiology (Modell et al 2015). There are recognized problems with this traditional model These include that set points can be changeable, that in most cases the underlying molecular or cellular mechanisms cannot be identified, and that in different circumstances a physiological variable may be regulated or behave as a controlled variable (e.g., pCO2 in the different circumstances of respiration and acid-base disturbance) (Modell et al 2015). To counter these difficulties the model of homeostasis has become complex including such concepts of allostasis and hierarchies of control (Modell et al 2015). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society

D Controlled parameter and controlling hormone levels

Method

Results

Discussion