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Too much of a good thing : why it is bad to stimulate the beta cell to secrete insulin

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journal contribution
posted on 01.01.2008, 00:00 authored by Kathryn Aston-MourneyKathryn Aston-Mourney, J Proietto, G Morahan, S Andrikopoulos
In many countries, first- or second-line pharmacological treatment of patients with type 2 diabetes consists of sulfonylureas (such as glibenclamide [known as glyburide in the USA and Canada]), which stimulate the beta cell to secrete insulin. However, emerging evidence suggests that forcing the beta cell to secrete insulin at a time when it is struggling to cope with the demands of obesity and insulin resistance may accelerate its demise. Studies on families with persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI), the primary defect of which is hypersecretion of insulin, have shown that overt diabetes can develop later in life despite normal insulin sensitivity. In addition, in vitro experiments have suggested that reducing insulin secretion from islets isolated from patients with diabetes can restore insulin pulsatility and improve function. This article will explore the hypothesis that forcing the beta cell to hypersecrete insulin may be counterproductive and lead to dysfunction and death via mechanisms that may involve the endoplasmic reticulum and oxidative stress. We suggest that, in diabetes, therapeutic approaches should be targeted towards relieving the demand on the beta cell to secrete insulin.

History

Journal

Diabetologia

Volume

51

Issue

4

Pagination

540 - 545

Publisher

Springer

Location

Heidelberg, Germany

ISSN

0012-186X

eISSN

1432-0428

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2008, Springer-Verlag