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

This Article Full Text Full Text (PDF) All Versions of this Article: JOE-08-0251v1 199/1/41    most recent Alert me when this article is cited Alert me if a correction is posted Services 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 Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Sargsyan, E. Articles by Bergsten, P. Search for Related Content PubMed PubMed Citation Articles by Sargsyan, E. Articles by Bergsten, P.

Department of Medical Cell Biology, Uppsala University, SE-75123, Uppsala, Sweden¹ Department of Clinical Science and Education, Karolinska Institutet, SE-11883, Stockholm, Sweden

(Correspondence should be addressed to P Bergsten Department of Medical Cell Biology, Uppsala University, Box 571, SE-75123 Uppsala, Sweden; Email: peter.bergsten{at}mcb.uu.se)

^* (E Sargsyan, H Ortsäter and K Thorn contributed equally to this work)

Elevated levels of glucose and lipids are characteristics of individuals with type 2 diabetes mellitus (T2DM). The enhanced nutrient levels have been connected with deterioration of β-cell function and impaired insulin secretion observed in these individuals. A strategy to improve β-cell function in individuals with T2DM has been intermittent administration of K_ATP channel openers. After such treatment, both the magnitude and kinetics of insulin secretion are markedly improved. In an attempt to further delineate mechanisms of how openers of K_ATP channels improve β-cell function, the effects of diazoxide on markers of endoplasmic reticulum (ER) stress was determined in β-cells exposed to the fatty acid palmitate. The eukaryotic translation factor 2-alpha kinase 3 (EIF2AK3; also known as PERK) and endoplasmic reticulum to nucleus signaling 1 (ERN1; also known as IRE1) pathways, but not the activating transcription factor (ATF6) pathway of the unfolded protein response, are activated in such lipotoxic β-cells. Inclusion of diazoxide during culture attenuated activation of the EIF2AK3 pathway but not the ERN1 pathway. This attenuation was associated with reduced levels of DNA-damage inducible transcript 3 (DDIT3; also known as CHOP) and β-cell apoptosis was decreased. It is concluded that reduction of ER stress may be a mechanism by which diazoxide improves β-cell function.

This article has been cited by other articles:

				L. Xu, F. Han, A. Mandal, G. N. Rao, and X. Zhang Diazoxide attenuates hypothermic preservation-induced renal injury via down-regulation of CHOP and caspase-12 Nephrol. Dial. Transplant., May 31, 2010; (2010) gfq298v1. [Abstract] [Full Text] [PDF]

				J. Lamontagne, E. Pepin, M.-L. Peyot, E. Joly, N. B. Ruderman, V. Poitout, S. R. M. Madiraju, C. J. Nolan, and M. Prentki Pioglitazone Acutely Reduces Insulin Secretion and Causes Metabolic Deceleration of the Pancreatic {beta}-Cell at Submaximal Glucose Concentrations Endocrinology, August 1, 2009; 150(8): 3465 - 3474. [Abstract] [Full Text] [PDF]