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AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic β-cell Apoptosis via Differential Downstream Mechanisms

The role of AMP-activated protein kinase (AMPK) in pancreatic β-cell apoptosis is still controversial, and the reasons for the discrepancies have not been clarified. In the current study, we observed the effects of two well-known AMPK activators 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR)...

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Autores principales: Dai, Yu-Lu, Huang, Su-Ling, Leng, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582151/
https://www.ncbi.nlm.nih.gov/pubmed/26435693
http://dx.doi.org/10.7150/ijbs.12108
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author Dai, Yu-Lu
Huang, Su-Ling
Leng, Ying
author_facet Dai, Yu-Lu
Huang, Su-Ling
Leng, Ying
author_sort Dai, Yu-Lu
collection PubMed
description The role of AMP-activated protein kinase (AMPK) in pancreatic β-cell apoptosis is still controversial, and the reasons for the discrepancies have not been clarified. In the current study, we observed the effects of two well-known AMPK activators 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and metformin, on apoptosis in rat insulinoma INS-1E cells, and further explored their possible mechanisms. Both AICAR and metformin protected INS-1E cells from palmitate-induced apoptosis, as reflected by decreases in both cleaved caspase 3 protein expression and caspase 3/7 activity, and these protective effects were abrogated by AMPK inhibitor compound C. The protective action of AICAR was probably mediated by the suppression of triacylglycerol accumulation, increase in Akt phosphorylation and decrease in p38 MAPK phosphorylation, while metformin might exert its protective effect on INS-1E cells by decreases in both JNK and p38 MAPK phosphorylation. All these regulations were dependent on AMPK activation. However, under standard culture condition, AICAR increased JNK phosphorylation and promoted INS-1E cell apoptosis in an AMPK-dependent manner, whereas metformin showed no effect on apoptosis. Our study revealed that AMPK activators AICAR and metformin exhibited different effects on INS-1E cell apoptosis under different culture conditions, which might be largely attributed to different downstream mediators. Our results provided new and informative clues for better understanding of the role of AMPK in β-cell apoptosis.
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spelling pubmed-45821512015-10-02 AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic β-cell Apoptosis via Differential Downstream Mechanisms Dai, Yu-Lu Huang, Su-Ling Leng, Ying Int J Biol Sci Research Paper The role of AMP-activated protein kinase (AMPK) in pancreatic β-cell apoptosis is still controversial, and the reasons for the discrepancies have not been clarified. In the current study, we observed the effects of two well-known AMPK activators 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and metformin, on apoptosis in rat insulinoma INS-1E cells, and further explored their possible mechanisms. Both AICAR and metformin protected INS-1E cells from palmitate-induced apoptosis, as reflected by decreases in both cleaved caspase 3 protein expression and caspase 3/7 activity, and these protective effects were abrogated by AMPK inhibitor compound C. The protective action of AICAR was probably mediated by the suppression of triacylglycerol accumulation, increase in Akt phosphorylation and decrease in p38 MAPK phosphorylation, while metformin might exert its protective effect on INS-1E cells by decreases in both JNK and p38 MAPK phosphorylation. All these regulations were dependent on AMPK activation. However, under standard culture condition, AICAR increased JNK phosphorylation and promoted INS-1E cell apoptosis in an AMPK-dependent manner, whereas metformin showed no effect on apoptosis. Our study revealed that AMPK activators AICAR and metformin exhibited different effects on INS-1E cell apoptosis under different culture conditions, which might be largely attributed to different downstream mediators. Our results provided new and informative clues for better understanding of the role of AMPK in β-cell apoptosis. Ivyspring International Publisher 2015-09-14 /pmc/articles/PMC4582151/ /pubmed/26435693 http://dx.doi.org/10.7150/ijbs.12108 Text en © 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Dai, Yu-Lu
Huang, Su-Ling
Leng, Ying
AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic β-cell Apoptosis via Differential Downstream Mechanisms
title AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic β-cell Apoptosis via Differential Downstream Mechanisms
title_full AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic β-cell Apoptosis via Differential Downstream Mechanisms
title_fullStr AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic β-cell Apoptosis via Differential Downstream Mechanisms
title_full_unstemmed AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic β-cell Apoptosis via Differential Downstream Mechanisms
title_short AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic β-cell Apoptosis via Differential Downstream Mechanisms
title_sort aicar and metformin exert ampk-dependent effects on ins-1e pancreatic β-cell apoptosis via differential downstream mechanisms
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582151/
https://www.ncbi.nlm.nih.gov/pubmed/26435693
http://dx.doi.org/10.7150/ijbs.12108
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