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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Adamantane, Animals, Cells, Cultured, Cellular Senescence, Cyclic AMP, Cyclic AMP Response Element-Binding Protein, Cyclic AMP-Dependent Protein Kinases, DNA Damage, Diabetes Mellitus, Dipeptidyl-Peptidase IV Inhibitors, Disease Models, Animal, Dose-Response Relationship, Drug, Endothelial Cells, Enzyme Activation, Exenatide, Glucagon-Like Peptide 1, Glucagon-Like Peptide-1 Receptor, Heme Oxygenase-1, Humans, Hydrogen Peroxide, Hypoglycemic Agents, Male, NAD(P)H Dehydrogenase (Quinone), Nitriles, Oxidants, Oxidative Stress, Peptides, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Pyrrolidines, Rats, Rats, Zucker, Reactive Oxygen Species, Receptors, Glucagon, Signal Transduction, Venoms, Vildagliptin.
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Does glucagon-like peptide 1 prevent reactive oxygen species-induced endothelial cell senescence through the activation of protein kinase A? Context: Endothelial cell senescence is an important contributor to vascular aging and is increased under diabetic conditions. Here we investigated whether the antidiabetic hormone glucagon-like peptide 1 (GLP-1) could prevent oxidative stress-induced cellular senescence in endothelial cells. In Zucker diabetic fatty rats, a significant 2-fold higher level of vascular senescence was observed compared with control lean rats. Dipeptidyl-peptidase 4 (DPP-4) inhibition significantly increased GLP-1 levels in these animals and reduced senescence almost to lean animal levels. In vitro studies with human umbilical vein endothelial cells showed that GLP-1 had a direct protective effect on oxidative stress (H(2)O(2))-induced senescence and was able to attenuate oxidative stress-induced DNA damage and cellular senescence. The GLP-1 analogue exendin-4 provided similar results, whereas exendin fragment 9-39, a GLP-1 receptor antagonist, abolished this effect. Intracellular signaling by the phosphoinositide 3-kinase (PI3K)/Akt survival pathway did not appear to be involved. Further analysis revealed that GLP-1 activates the cAMP response element-binding (CREB) transcription factor in a cAMP/protein kinase A (PKA)-dependent manner, and inhibition of the cAMP/PKA pathway abolished the GLP-1 protective effect. Expression analysis revealed that GLP-1 can induce the oxidative defense genes HO-1 and NQO1.
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Dipeptidyl-peptidase 4 inhibition protects against vascular senescence in a diabetic rat model. In vitro studies with human umbilical vein endothelial cells showed that reactive oxygen species-induced senescence was attenuated by GLP-1 in a receptor-dependent manner involving downstream PKA signaling and induction of antioxidant genes. Final Decision: yes