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 Presentation

"Insulin Resistance and Glucose Allostasis"

Prof. Michael Stumvoll (biography)
English - 2005-04-14 - 34 minutes
(28 slides)

Summary :
Maintance of glycemia is of vital importance. Regulation of glycemia is accomplished by the balanced interplay between insulin action and insulin secretion. It is common belief that in healthy humans plasma glucose concentration is regulated by a homeostatic system, i.e. a system designed to maintain plasma glucose concentration constant. Here we review evidence that in response to a chronic perturbation such as insulin resistance (a common consequence of obesity) the glucose system is regulated allostatically to maintain acute homeostasis. We demonstrate that despite normal compensatory regulation, plasma glucose concentration must increase to continuously inform the beta cell of the presence of insulin resistance so it can maintain the increased secretory response. Movement along the hyperbola which indicates perfect compensation in response to changes in insulin action is inevitably accompanied by changes in glycemia (5 year follow up data from healthy normal glucose tolerant Pima Indians, figure). Due to glucotoxicity, over time this normal physiologic increase in glycemia (glucose allostasis) may well have pathophysiologic consequences such as contributing to the development of type 2 diabetes (allostatic overload).

Learning objectives :
After viewing this presentation, participants will be able to discuss:
• The variation of serum glucose levels with different degrees of insulin resistance (IR)
• The signals that may be responsible for the increase beta cell response to IR
• The definition of the Disposition Index (DI)
• The definition of the Beta Cell Demand Index (BCDI)
• The relationship of both the DI and the BCDI to serum glucose levels

Bibliographic references :
Michael Stumvoll, P. Antonio Tataranni, Norbert Stefan, Barbora Vozarova, and Clifton Bogardus Glucose Allostasis Diabetes 52:903-909, 2003

Stumvoll M, Tataranni PA, Bogardus C. The hyperbolic law--a 25-year perspective. Diabetologia. 2005 Feb;48(2):207-9.

Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005 Apr;365(9467):1333-46.

Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest. 1999 Sep;104(6):787-94.

Goran MI, Gower BA. Longitudinal study on pubertal insulin resistance. Diabetes. 2001 Nov;50(11):2444-50

   


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