Restoring a functional beta-cell mass in diabetes.
Type 1 and type 2 diabetes have often been presented as disease forms that profoundly differ in the presence and pathogenic significance of a reduced beta-cell mass. We review evidence indicating that the beta-cell mass in type 1 diabetes is usually not decreased by at least 90% at clinical onset, and remains often detectable for years after diagnosis at age above 15 years. Clinical and experimental evidence also exists for a reduced beta-cell mass in type 2 diabetes where it can be the cause for and/or the consequence of dysregulated beta-cell functions. With beta-cell mass defined as number of beta-cells, these views face the limitation of insufficient data and methods for human organs. Because beta-cells can occur under different phenotypes that vary with age and with environmental conditions, we propose to use the term functional beta-cell mass as an assessment of a beta-cell population by the number of beta-cells and their phenotype or functional state. Assays exist to measure functional beta-cell mass in isolated preparations. We selected a glucose-clamp test to evaluate functional beta-cell mass in type 1 patients at clinical onset and in type 1 recipients following intraportal islet cell transplantation. Comparison of the data with those in non-diabetic controls helps targeting and monitoring of therapeutic interventions.
Diabetes Research Center, Brussels Free University-VUB, JDRF Center for Beta Cell Therapy in Diabetes, Brussels, Belgium. Daniel.Pipeleers@vub.ac.be
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D
Pipeleers
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Chintinne
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B
Denys
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G
Martens
B
B
Keymeulen
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Gorus
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000503:physiopathology; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008297:Male; D012038:Regeneration / Q000187:drug effects; D016896:Treatment Outcome
D001786:Blood Glucose; D007328:Insulin