HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ling, Z. Articles by Pipeleers, D. Search for Related Content PubMed PubMed Citation Articles by Ling, Z. Articles by Pipeleers, D. Social Bookmarking                What's this?

Glibenclamide Treatment Recruits ß-Cell Subpopulation Into Elevated and Sustained Basal Insulin Synthetic Activity

Diabetes Research Center, Brussels Free University, Vrije Universiteit Brussels, Brussels, Belgium

Address correspondence and reprint requests to Daniel Pipeleers, MD, PhD, Diabetes Research Center, Brussels Free University-Vrije Universiteit Brussels, Laarbeeklaan 103, B-1090 Brussels, Belgium. E-mail: daniel.pipeleers{at}vub.ac.be

Abbreviations: FACS, fluorescence-activated cell sorting

Use of sulfonylureas in diabetes treatment is based on their insulin-releasing effect on pancreatic ß-cells. Prolonged action is known to degranulate ß-cells, but functional consequences have not been examined at the cellular level. This study investigates influences of in vivo (48-h) and in vitro (24-h) glibenclamide treatment on the functional state of the ß-cell population. Both conditions decreased cellular insulin content by >50% and caused an elevated basal insulin biosynthetic activity that was maintained for at least 24 h after drug removal. Glibenclamide stimulation of basal insulin synthesis was not achieved after a 2-h exposure; it required a calcium-dependent translational activity and involved an increase in the percent activated ß-cells (50% after glibenclamide pretreatment vs. 8% in control cells). The glibenclamide-activated ß-cell subpopulation corresponded to the degranulated ß-cell subpopulation that was isolated by fluorescence-activated cell sorter on the basis of lower cellular sideward scatter. Glibenclamide pretreatment did not alter cellular rates of glucose oxidation but sensitized ß-cells to glucose-induced changes in metabolic redox and insulin synthesis and release. In conclusion, chronic exposure to glibenclamide results in degranulation of a subpopulation of ß-cells, which maintain an elevated protein and insulin synthetic activity irrespective of the presence of the drug and of glucose. Our study demonstrates that the in situ ß-cell population also exhibits a functional heterogeneity that can vary with drug treatment. Glibenclamide induces degranulated ß-cells with a sustained elevated basal activity that might increase the risk for hypoglycemic episodes.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. El Ouaamari, N. Baroukh, G. A. Martens, P. Lebrun, D. Pipeleers, and E. van Obberghen miR-375 Targets 3'-Phosphoinositide-Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic {beta}-Cells Diabetes, October 1, 2008; 57(10): 2708 - 2717. [Abstract] [Full Text] [PDF]

				G. A. Martens, Q. Wang, K. Kerckhofs, G. Stange, Z. Ling, and D. Pipeleers Metabolic Activation of Glucose Low-Responsive {beta}-Cells by Glyceraldehyde Correlates with Their Biosynthetic Activation in Lower Glucose Concentration Range But Not at High Glucose Endocrinology, November 1, 2006; 147(11): 5196 - 5204. [Abstract] [Full Text] [PDF]