title: Glucose homeostasis with infinite gain: further lessons from the Daisyworld parable?
abstract: A major unresolved physiological problem is how the rate of hepatic glucose production is increased to match the increased rate of glucose utilization during exercise without a change in arterial blood glucose level. A homeostat with such capabilities is said to have infinite gain. Daisyworld is an imaginary planet orbiting a variable star. The only life is black and white daisies. Black daisies retain heat, slightly warming the planet; white daisies cool it. When the two types of daisies grow best at slightly different temperatures, variations in solar luminosity (over a wide range) cause the ratio of white:black daisies to vary in a manner that keeps the planetary temperature constant. This model therefore achieves infinite gain by having two opposing but interdependent controllers. Here we suggest that the pancreatic islet alpha- and beta-cells might act as black and white daisies. For the analogy to apply, glucagon and insulin must not only have opposing effects on the blood sugar concentration, but the secretion of the one has, at some quantum level, to be at the expense of the other. Electrical coupling between heterocellular groups of alpha- and beta-cells within the pancreatic islets suggests that this might indeed be the case. alpha-Cell activity must, furthermore, promote secretory activity in other alpha-cells; similarly with beta-cells. This is probably mediated via pancreastatin and gamma-amino butyric acid (GABA) which are paracrinically co-secreted with glucagon and insulin, respectively. alpha-Cell activity spreads (at the expense of beta-cell activity) when the blood glucose level is below set point, while beta-cell activity progressively replaces alpha-cell activity above set point. At set point changes in the ratio of alpha:beta-cell activity are inhibited.
authors.affiliation: Department of Medical Physiology and Biochemistry, University of Stellenbosch, Tygerberg, South Africa.
authors.forename: J H
authors.initials: JH
authors.lastname: Koeslag
authors.forename: P T
authors.initials: PT
authors.lastname: Saunders
authors.forename: J A
authors.initials: JA
authors.lastname: Wessels
mesh_terms: D053379:Chromogranin A; D005934:Glucagon / Q000502:physiology; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008954:Models, Biological; D010187:Pancreatic Hormones / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D053379:Chromogranin A; D007328:Insulin; D010187:Pancreatic Hormones; C050836:pancreastatin; D005680:gamma-Aminobutyric Acid; D005934:Glucagon; D005947:Glucose