title: Too much of a good thing: why it is bad to stimulate the beta cell to secrete insulin.
abstract: 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.
authors.affiliation: The University of Melbourne Department of Medicine (AH/NH), Heidelberg Repatriation Hospital, Building 24, 300 Waterdale Road, Heidelberg Heights VIC 3081, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Aston-Mourney
authors.forename: J
authors.initials: J
authors.lastname: Proietto
authors.forename: G
authors.initials: G
authors.lastname: Morahan
authors.forename: S
authors.initials: S
authors.lastname: Andrikopoulos
mesh_terms: D003920:Diabetes Mellitus / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications / Q000209:etiology / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress
chemical_list: D007328:Insulin