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This Article Full Text Full Text (PDF) All Versions of this Article: 92/3/481    most recent expphysiol.2006.034835v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McClenaghan, N. H. Search for Related Content PubMed PubMed Citation Articles by McClenaghan, N. H. Related Collections Neuroendocrinology/Endocrinology Lectures

¹ School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK

Abstract

Knowledge about the sites and actions of the numerous physiological and pharmacological factors affecting insulin secretion and pancreatic ß-cell function has been derived from the use of bioengineered insulin-producing cell lines. Application of an innovative electrofusion approach has generated novel glucose-responsive insulin-secreting cells for pharmaceutical and experimental research, including popular BRIN-BD11 ß-cells. This review gives an overview of the establishment and core characteristics of clonal electrofusion-derived BRIN-BD11 ß-cells. As discussed, BRIN-BD11 cells have facilitated studies aimed at dissecting important pathways by which nutrients and other bioactive molecules regulate the complex mechanisms regulating insulin secretion, and highlight the future potential of novel and diverse bioengineering approaches to provide a cell-based insulin-replacement therapy for diabetes. Clonal BRIN-BD11 ß-cells have been instrumental in: (a) characterization of K_ATP channel-dependent and -independent actions of nutrients and established and emerging insulinotropic antidiabetic drugs, and the understanding of drug-induced ß-cell desensitization; (b) tracing novel metabolic and ß-cell secretory pathways, including use of state-of-the-art NMR approaches to provide new insights into the relationships between glucose and amino acid handling and insulin secretion; and (c) determination of the chronic detrimental actions of nutrients and the diabetic environment on pancreatic ß-cells, including the recent discovery that homocysteine, a risk factor for metabolic syndrome, may play a role in the progressive demise of insulin secretion and pancreatic ß-cell function in diabetes. Collectively, the studies discussed in this review highlight the importance of innovative experimental ß-cell physiology in the discovery and characterization of new and improved drugs and therapeutic strategies to help tackle the emerging diabetes epidemic.

(Received 28 September 2006; accepted after revision 1 February 2007; first published online 1 February 2007)
Corresponding author N. H. McClenaghan: School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK. Email: nh.mcclenaghan{at}ulster.ac.uk

This lecture was given at the Main meeting of the Physiological Society at University College London on Wednesday 5th July 2006.

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