Glucose allostasis.
In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-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.
Stumvoll
Michael
M
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA. michael.stumvoll@med.uni-tuebingen.de
Tataranni
P Antonio
PA
Stefan
Norbert
N
Vozarova
Barbora
B
Bogardus
Clifton
C
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D005215:Fasting; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007198:Indians, North American; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors
D001786:Blood Glucose; D007328:Insulin