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 Donath, M. Y. Articles by Reinecke, M. Search for Related Content PubMed PubMed Citation Articles by Donath, M. Y. Articles by Reinecke, M. Social Bookmarking                What's this?

Mechanisms of ß-Cell Death in Type 2 Diabetes

¹ Division of Endocrinology and Diabetes, University Hospital Zurich, Zurich, Switzerland
² Division of Neuroendocrinology, Institute of Anatomy, University of Zurich, Zurich, Switzerland

A decrease in the number of functional insulin-producing ß-cells contributes to the pathophysiology of type 2 diabetes. Opinions diverge regarding the relative contribution of a decrease in ß-cell mass versus an intrinsic defect in the secretory machinery. Here we review the evidence that glucose, dyslipidemia, cytokines, leptin, autoimmunity, and some sulfonylureas may contribute to the maladaptation of ß-cells. With respect to these causal factors, we focus on Fas, the ATP-sensitive K⁺ channel, insulin receptor substrate 2, oxidative stress, nuclear factor-B, endoplasmic reticulum stress, and mitochondrial dysfunction as their respective mechanisms of action. Interestingly, most of these factors are involved in inflammatory processes in addition to playing a role in both the regulation of ß-cell secretory function and cell turnover. Thus, the mechanisms regulating ß-cell proliferation, apoptosis, and function are inseparable processes.

Abbreviations: ER, endoplasmic reticulum; FLIP, FLICE inhibitory protein; IL, interleukin; K_ATP channel, ATP-sensitive K⁺ channel; NF, nuclear factor

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

This article has been cited by other articles:

				H. Ghanaat-Pour, Z. Huang, M. Lehtihet, and A. Sjoholm Global expression profiling of glucose-regulated genes in pancreatic islets of spontaneously diabetic Goto-Kakizaki rats J. Mol. Endocrinol., August 1, 2007; 39(2): 135 - 150. [Abstract] [Full Text] [PDF]

				A. Hambrock, C. B. de Oliveira Franz, S. Hiller, A. Grenz, S. Ackermann, D. U. Schulze, G. Drews, and H. Osswald Resveratrol Binds to the Sulfonylurea Receptor (SUR) and Induces Apoptosis in a SUR Subtype-specific Manner J. Biol. Chem., February 2, 2007; 282(5): 3347 - 3356. [Abstract] [Full Text] [PDF]

				M. Y. Donath and J. A. Ehses Type 1, type 1.5, and type 2 diabetes: NOD the diabetes we thought it was PNAS, August 15, 2006; 103(33): 12217 - 12218. [Full Text] [PDF]