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AMP-activated protein kinase and pancreatic/duodenal homeobox-1 involved in insulin secretion under high leucine exposure in rat insulinoma β-cells

The effect of leucine on glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells is quite controversial, and mechanism involved in the effect has not been elucidated yet. Consequently, we aimed to investigate effect of leucine on GSIS and its mechanism focusing on contribution of AMP-activ...

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Autores principales: Zhang, Xiujuan, Sun, Nannan, Wang, Laicheng, Guo, Hua, Guan, Qingbo, Cui, Bin, Tian, Limin, Gao, Ling, Zhao, Jiajun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822882/
https://www.ncbi.nlm.nih.gov/pubmed/19438972
http://dx.doi.org/10.1111/j.1582-4934.2009.00656.x
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author Zhang, Xiujuan
Sun, Nannan
Wang, Laicheng
Guo, Hua
Guan, Qingbo
Cui, Bin
Tian, Limin
Gao, Ling
Zhao, Jiajun
author_facet Zhang, Xiujuan
Sun, Nannan
Wang, Laicheng
Guo, Hua
Guan, Qingbo
Cui, Bin
Tian, Limin
Gao, Ling
Zhao, Jiajun
author_sort Zhang, Xiujuan
collection PubMed
description The effect of leucine on glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells is quite controversial, and mechanism involved in the effect has not been elucidated yet. Consequently, we aimed to investigate effect of leucine on GSIS and its mechanism focusing on contribution of AMP-activated protein kinase (AMPK) and pancreatic/duodenal homeobox-1 (PDX-1). Rat insulinoma β-cells (INS-1, RIN m5F, DN-PDX-1#28 and PDX-1#6) were cultured with or without leucine, AICAR (AMPK agonist) or compound C (AMPK antagonist) for 48 hrs. In contrast to control, AICAR treatment decreased GSIS at high glucose and insulin content, also impaired protein and mRNA expression of PDX-1 and its downstream targets, glucokinase (GCK) and glucose transporter 2 (GLUT2). Compound C treatment had the opposite effects. We observed that neither AICAR nor compound C could affect expression of GCK and GLUT2 when PDX-1 expression was absent. Chronic leucine exposure inhibited GSIS at high glucose and insulin content in a dose-dependent manner, concomitant with an increase in AMPK and a decrease in PDX-1, GCK and GLUT2. The inhibitory effects of leucine was potentiated by AICAR treatment and rescued by compound C treatment. Finally, the inhibition of PDX-1 could potentiate the impaired effects induced by leucine whereas overexpression of PDX-1 could protect the cell from impairment induced by leucine. The study indicated that chronic leucine might result in an increase in AMPK and then a decrease in PDX-l, in turn to depress GCK and GLUT2 resulting in decreased GSIS at high glucose and insulin content.
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spelling pubmed-38228822015-04-27 AMP-activated protein kinase and pancreatic/duodenal homeobox-1 involved in insulin secretion under high leucine exposure in rat insulinoma β-cells Zhang, Xiujuan Sun, Nannan Wang, Laicheng Guo, Hua Guan, Qingbo Cui, Bin Tian, Limin Gao, Ling Zhao, Jiajun J Cell Mol Med Articles The effect of leucine on glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells is quite controversial, and mechanism involved in the effect has not been elucidated yet. Consequently, we aimed to investigate effect of leucine on GSIS and its mechanism focusing on contribution of AMP-activated protein kinase (AMPK) and pancreatic/duodenal homeobox-1 (PDX-1). Rat insulinoma β-cells (INS-1, RIN m5F, DN-PDX-1#28 and PDX-1#6) were cultured with or without leucine, AICAR (AMPK agonist) or compound C (AMPK antagonist) for 48 hrs. In contrast to control, AICAR treatment decreased GSIS at high glucose and insulin content, also impaired protein and mRNA expression of PDX-1 and its downstream targets, glucokinase (GCK) and glucose transporter 2 (GLUT2). Compound C treatment had the opposite effects. We observed that neither AICAR nor compound C could affect expression of GCK and GLUT2 when PDX-1 expression was absent. Chronic leucine exposure inhibited GSIS at high glucose and insulin content in a dose-dependent manner, concomitant with an increase in AMPK and a decrease in PDX-1, GCK and GLUT2. The inhibitory effects of leucine was potentiated by AICAR treatment and rescued by compound C treatment. Finally, the inhibition of PDX-1 could potentiate the impaired effects induced by leucine whereas overexpression of PDX-1 could protect the cell from impairment induced by leucine. The study indicated that chronic leucine might result in an increase in AMPK and then a decrease in PDX-l, in turn to depress GCK and GLUT2 resulting in decreased GSIS at high glucose and insulin content. Blackwell Publishing Ltd 2009-04 2009-04-22 /pmc/articles/PMC3822882/ /pubmed/19438972 http://dx.doi.org/10.1111/j.1582-4934.2009.00656.x Text en © 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Articles
Zhang, Xiujuan
Sun, Nannan
Wang, Laicheng
Guo, Hua
Guan, Qingbo
Cui, Bin
Tian, Limin
Gao, Ling
Zhao, Jiajun
AMP-activated protein kinase and pancreatic/duodenal homeobox-1 involved in insulin secretion under high leucine exposure in rat insulinoma β-cells
title AMP-activated protein kinase and pancreatic/duodenal homeobox-1 involved in insulin secretion under high leucine exposure in rat insulinoma β-cells
title_full AMP-activated protein kinase and pancreatic/duodenal homeobox-1 involved in insulin secretion under high leucine exposure in rat insulinoma β-cells
title_fullStr AMP-activated protein kinase and pancreatic/duodenal homeobox-1 involved in insulin secretion under high leucine exposure in rat insulinoma β-cells
title_full_unstemmed AMP-activated protein kinase and pancreatic/duodenal homeobox-1 involved in insulin secretion under high leucine exposure in rat insulinoma β-cells
title_short AMP-activated protein kinase and pancreatic/duodenal homeobox-1 involved in insulin secretion under high leucine exposure in rat insulinoma β-cells
title_sort amp-activated protein kinase and pancreatic/duodenal homeobox-1 involved in insulin secretion under high leucine exposure in rat insulinoma β-cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822882/
https://www.ncbi.nlm.nih.gov/pubmed/19438972
http://dx.doi.org/10.1111/j.1582-4934.2009.00656.x
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