Journal Article

GLP-1 and Ghrelin Attenuate High Glucose/High Lipid-Induced Apoptosis and Senescence of Human Microvascular Endothelial Cells

Zheng, Yuehong, Liao, Pengzhi, Yang, Dan, Liu, Duan

2017

Overview

Background/Aims: GLP-1 and ghrelin are common appetite-regulating hormones. Both have multiple functions beyond metabolic regulation. However, the effects of GLP-1 and ghrelin on endothelial biology are not fully understood. Here, we investigate the roles of GLP-1 and ghrelin in microvascular endothelial apoptosis and senescence. Methods: Human microvascular endothelial cells (HMECs) were exposed to high glucose/high lipid (HG/HL) conditions and treated with GLP-1 or ghrelin. Cellular apoptosis, senescence, and mitochondrial function were measured. In addition, the MAPK and Akt signaling pathways were examined. Results: Both GLP-1 and ghrelin treatment decreased the number of TUNEL-positive cells and inhibited caspase-3 and PARP cleavage and mitochondrial dysfunction in HG/HL-exposed HMECs. GLP-1, but not ghrelin decreased the number of β-galactosidase (β-gal)-positive cells. Furthermore, GLP-1 and ghrelin inhibited ERK1/2, JNK1/2, and p38 signaling. GLP-1 suppressed Akt signaling, but ghrelin had no effect. Moreover, JNK1/2 and p38 inhibitors, but not ERK1/2 and Akt inhibitors, decreased the number of TUNEL-positive cells. Additionally, only the Akt inhibitor decreased the number of β-gal-positive cells. Conclusion: These results demonstrate that GLP-1 and ghrelin inhibit mitochondrial dysfunction under HG/HL conditions, and suppress endothelial apoptosis via inhibiting JNK1/2 and p38 signaling; moreover, GLP-1 alleviates endothelial senescence via inactivating Akt signaling.

• Publisher: S. Karger AG,Cell Physiol Biochem Press GmbH & Co KG
• Subject: Angiogenesis / Apoptosis / Apoptosis - drug effects / Atherosclerosis / Cardiomyocytes / Caspase 3 - metabolism / Cell growth / Cells, Cultured / Cellular Senescence - drug effects / Diabetes / Diabetic retinopathy / Endothelial Cells - cytology / Endothelial Cells - metabolism / Experiments / Ghrelin / Ghrelin - pharmacology / Glp-1 / Glucagon-Like Peptide 1 - pharmacology / Glucose - pharmacology / Humans / Kinases / Lipids / Lipids - pharmacology / Metabolism / Microvascular endothelial cells / Microvessels - cytology / Mitochondria - drug effects / Mitochondria - metabolism / Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors / Mitogen-Activated Protein Kinase 1 - metabolism / Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors / Mitogen-Activated Protein Kinase 3 - metabolism / Mitogen-Activated Protein Kinase 8 - antagonists & inhibitors / Mitogen-Activated Protein Kinase 8 - metabolism / Mitogen-Activated Protein Kinase 9 - antagonists & inhibitors / Mitogen-Activated Protein Kinase 9 - metabolism / Neurosciences / Nitric oxide / Original Paper / p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors / p38 Mitogen-Activated Protein Kinases - metabolism / Poly(ADP-ribose) Polymerases - metabolism / Protein Kinase Inhibitors - pharmacology / Proto-Oncogene Proteins c-akt - antagonists & inhibitors / Proto-Oncogene Proteins c-akt - metabolism / Reactive Oxygen Species - metabolism / Rodents / Senescence / Signal Transduction - drug effects