Glucose allostasis

Michael Stumvoll, P Antonio Tataranni, Norbert Stefan, Barbora de Courten, Clifton Bogardus

Research output: Contribution to journalArticleResearchpeer-review

82 Citations (Scopus)

Abstract

In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic β-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy individuals with normal glucose tolerance, normoglycemia can always be maintained by compensatorily increasing AIR in response to decreasing M (and vice versa). This has been mathematically described by the hyperbolic relationship between AIR and M and referred to as glucose homeostasis, with glucose concentration assumed to remain constant along the hyperbola. Conceivably, glucose is one of the signals stimulating AIR in response to decreasing M. Hypothetically, as with any normally functioning feed-forward system, AIR should not fully compensate for worsening M, since this would remove the stimulus for the compensation. We provide evidence from cross-sectional, longitudinal, and prospective data from Pima Indians (n = 413) and Caucasians (n = 60) that fasting and postprandial glucose concentrations increase with decreasing M despite normal compensation of AIR. For this physiologic adaptation to chronic stress (insulin resistance), we propose to use the term "glucose allostasis." Allostasis (stability through change) ensures the continued homeostatic response (stability through staying the same) to acute stress at some cumulative costs to the system. With increasing severity and over time, the allostatic load (increase in glycemia) may have pathological consequences, such as the development of type 2 diabetes.

Original languageEnglish
Pages (from-to)903-909
Number of pages7
JournalDiabetes
Volume52
Issue number4
DOIs
Publication statusPublished - 1 Apr 2003

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