Cyclic AMP-mediated pleiotropic effects of glucagon-like peptide-1 receptor activation. Focus on “Exendin-4 attenuates high glucose-induced cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and activation of SERCA2a”

2013 ◽  
Vol 304 (6) ◽  
pp. C505-C507 ◽  
Author(s):  
Yumei Ye ◽  
Yochai Birnbaum
Keyword(s):  
Endoplasmic Reticulum ◽  
Cyclic Amp ◽  
Endoplasmic Reticulum Stress ◽  
High Glucose ◽  
Receptor Activation ◽  
Pleiotropic Effects ◽  
Cardiomyocyte Apoptosis ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Glucagon-Like Peptide-1 Agonists Protect Pancreatic β-Cells From Lipotoxic Endoplasmic Reticulum Stress Through Upregulation of BiP and JunB

Diabetes ◽  
2009 ◽  
Vol 58 (12) ◽  
pp. 2851-2862 ◽  
Author(s):  
Daniel A. Cunha ◽  
Laurence Ladrière ◽  
Fernanda Ortis ◽  
Mariana Igoillo-Esteve ◽  
Esteban N. Gurzov ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract 205: Mitochondrial Sirt3 Is Upregulated By Glucagon-like Peptide-1 Receptor Activation And Contributes To Reversal Of Cardiac Mitochondrial Remodeling Induced By Type 2 Diabetes.

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Akio Monji ◽  
Yasuko K Bando ◽  
Haruya Kawase ◽  
Morihiko Aoyama ◽  
Toyoaki Murohara
Keyword(s):  
Cyclic Amp ◽  
Receptor Activation ◽  
Reverse Remodeling ◽  
Mitochondrial Morphology ◽  
Dependent Manner ◽  
Diabetic Mice ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Mitochondrial Remodeling

RATIONALE: Sirtuin 3 (SIRT3) is a mitochondrial protein deacetylase that maintains basal ATP yield and its expression level is increased by fasting, exercise, and some NAD+ intermediates. We recently reported that the glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 (Ex-4) ameliorated cardiac mitochondrial remodeling in diabetic cardiomyopathy via increase in cardiac cyclic AMP (AJP2013). Because changes in cyclic AMP level is regulated by adenylyl cyclase which is one of the downstream target of Ex-4, we hypothesized that SIRT3 may involve in the Ex-4-mediated myocardial reverse remodeling of mitochondria in diabetic mice. METHODS: Type 2 diabetic Mice (16-week old male) were allocated into experimental groups as follows: Ex-4 (24 nmole/kg/day, subcutaneously administrated by osmotic pump for 40 days, DIO/Ex-4) and vehicle control (DIO/CON). Heart samples and cultured rat neonatal cardiomyocytes were subjected to mitochondrial fractionation using density gradient. RESULTS: Cardiac cyclic AMP concentration and phosphorylation of CREB were elevated in DIO-ex4, suggesting successful administration of Ex-4. Electron microscopic analysis revealed that Ex-4 reversed destroyed cristae structure and defragmented mitochondria of DIO/CON heart. The ratio of expression levels of Mitofusin-1 (Mfn1) and mitofusin-2 (Mfn2) was consistently suppressed by Ex-4 treatment, suggesting normalization of mitochondrial morphology. Of note, DIO-CON exhibited marked decrease in cardiac SIRT3 level compared to lean/nondiabetic counterpart, which was reversed by exendin-4 treatment. Pharmacological production of intracellular cAMP levels (Isoprotelenol (10 microM) and 8-bromo-cyclic AMP (1 mM)) increased SIRT3 mRNA in cultured primary cardiomyocytes. The AMP-activated protein kinase (AMPK) inhibitition blocked the increase in SIRT3 mRNA, indicating that the SIRT3 expression was regulated by AMPK-dependent manner. CONCLUSIONS: Our results indicate that Ex-4 reversed abnormal suppression of SIRT3 in mitochondria via activating the PKA/AMPK-dependent pathway.

Glucagon-like peptide-1 production in the GLUTag cell line is impaired by free fatty acids via endoplasmic reticulum stress

Metabolism ◽  
2014 ◽  
Vol 63 (6) ◽  
pp. 800-811 ◽  
Author(s):  
Hiroto Hayashi ◽  
Ren Yamada ◽  
Siddhartha Shankar Das ◽  
Taiki Sato ◽  
Aki Takahashi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Free Fatty Acids ◽  
Cell Line ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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