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Too much of a good thing : why it is bad to stimulate the beta cell to secrete insulin
journal contribution
posted on 2008-01-01, 00:00 authored by Kathryn Aston-MourneyKathryn Aston-Mourney, J Proietto, G Morahan, S AndrikopoulosIn 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
DiabetologiaVolume
51Issue
4Pagination
540 - 545Publisher
SpringerLocation
Heidelberg, GermanyPublisher DOI
Link to full text
ISSN
0012-186XeISSN
1432-0428Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2008, Springer-VerlagUsage metrics
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No categories selectedKeywords
C57BL\/6DBA\/2endoplasmic reticulum stresshypersecretionhyperinsulinaemiainsulinIslet dysfunctionoxidative stressScience & TechnologyLife Sciences & BiomedicineEndocrinology & MetabolismENDOPLASMIC-RETICULUM STRESSACTIVATING GLUCOKINASE MUTATIONGLUCOSE-HOMEOSTASISDIABETES-MELLITUSSULFONYLUREA RECEPTOR-1PANCREATIC-ISLETSTYPE-2MOUSEGENEAPOPTOSIS
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