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

This Article Accepted manuscript (PDF) All Versions of this Article: JME-08-0006v1 41/3/187    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 Google Scholar Google Scholar Articles by Nyblom, H. Articles by Bergsten, P. Search for Related Content PubMed PubMed Citation Articles by Nyblom, H. Articles by Bergsten, P.

H Nyblom, Medical Cell Biology, Uppsala University, Uppsala, 75123, Sweden
E Sargsyan, Medical Cell Biology, Uppsala University, Uppsala, Sweden
P Bergsten, Medical Cell Biology, Uppsala University, Uppsala, Sweden

Correspondence: Hanna Nyblom, Email: Hanna.Nyblom{at}mcb.uu.se

Abstract

Prolonged hyperglycaemia leads to impaired glucose-stimulated insulin secretion (GSIS) and apoptosis in insulin-producing β-cells. The detrimental effects have been connected with glucose-induced lipid accumulation in the β-cell. AMP-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) promotes utilization of nutrient stores for energy production. It was tested how impaired GSIS and elevated apoptosis observed in INS-1E cells after prolonged culture at 27 mM glucose was affected by inclusion of 0.3 or 1 mM AICAR during culture. Glucose-induced impairment of insulin release was reverted by inclusion of 0.3 but not 1 mM AICAR, which did not affect insulin content. The glucose-induced rise in triglyceride content observed in cells cultured at 27 mM glucose was not altered by inclusion of either 0.3 or 1 mM AICAR. Inclusion of 1 but not 0.3 mM AICAR during culture induced phosphorylation of AMPK and its down-stream target acyl-CoA carboxylase. Phosphorylation was paralleled by reduced number of apoptotic cells and lowered expression of pro-apoptotic protein CHOP. In conclusion, AICAR dose-dependently improves β-cell function and reduces apoptosis in β-cells exposed to prolonged hyperglycaemia without changing triglyceride levels.

This article has been cited by other articles:

				A. Zulli, E. Lau, B. P.P. Wijaya, X. Jin, K. Sutarga, G. D. Schwartz, J. Learmont, P. J. Wookey, A. Zinellu, C. Carru, et al. High Dietary Taurine Reduces Apoptosis and Atherosclerosis in the Left Main Coronary Artery: Association With Reduced CCAAT/Enhancer Binding Protein Homologous Protein and Total Plasma Homocysteine but not Lipidemia Hypertension, June 1, 2009; 53(6): 1017 - 1022. [Abstract] [Full Text] [PDF]