We have located links that may give you full text access.
Journal Article
Research Support, Non-U.S. Gov't
GLP-1 Receptor Activation Inhibits Palmitate-Induced Apoptosis via Ceramide in Human Cardiac Progenitor Cells.
Journal of Clinical Endocrinology and Metabolism 2017 November 2
Context: Increased apoptosis of cardiomyocytes and cardiac progenitor cells (CPCs) in response to saturated fatty acids (SFAs) can lead to myocardial damage and dysfunction. Ceramides mediate lipotoxicity-induced apoptosis. Glucagonlike peptide-1 receptor (GLP1R) agonists exert beneficial effects on cardiac cells in experimental models.
Objective: To investigate the protective effects of GLP1R activation on SFA-mediated apoptotic death of human CPCs.
Design: Human CPCs were isolated from cardiac appendages of nondiabetic donors and then exposed to palmitate with or without pretreatment with the GLP1R agonist exendin-4. Ceramide accumulation was evaluated by immunofluorescence. Expression of key enzymes in de novo ceramide biosynthesis was studied by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Apoptosis was evaluated by measuring release of oligonucleosomes, caspase-3 cleavage, caspase activity, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling.
Results: Exposure of the CPCs to palmitate resulted in 2.3- and 1.9-fold higher expression of ceramide synthase 5 (CERS5) and ceramide desaturase-1, respectively (P < 0.05). This was associated with intracellular accumulation of ceramide and activation of c-Jun NH2-terminal protein kinase (JNK) signaling and apoptosis (P < 0.05). Both coincubation with fumonisin B1, a specific ceramide synthase inhibitor, and CERS5 knockdown prevented ceramide accumulation, JNK activation, and apoptosis in response to palmitate (P < 0.05). Exendin-4 also prevented the activation of the ceramide biosynthesis and JNK in response to palmitate, inhibiting apoptosis (P < 0.05).
Conclusions: Excess palmitate results in activation of ceramide biosynthesis, JNK signaling, and apoptosis in human CPCs. GLP1R activation counteracts this lipotoxic damage via inhibition of ceramide generation, and this may represent a cardioprotective mechanism.
Objective: To investigate the protective effects of GLP1R activation on SFA-mediated apoptotic death of human CPCs.
Design: Human CPCs were isolated from cardiac appendages of nondiabetic donors and then exposed to palmitate with or without pretreatment with the GLP1R agonist exendin-4. Ceramide accumulation was evaluated by immunofluorescence. Expression of key enzymes in de novo ceramide biosynthesis was studied by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Apoptosis was evaluated by measuring release of oligonucleosomes, caspase-3 cleavage, caspase activity, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling.
Results: Exposure of the CPCs to palmitate resulted in 2.3- and 1.9-fold higher expression of ceramide synthase 5 (CERS5) and ceramide desaturase-1, respectively (P < 0.05). This was associated with intracellular accumulation of ceramide and activation of c-Jun NH2-terminal protein kinase (JNK) signaling and apoptosis (P < 0.05). Both coincubation with fumonisin B1, a specific ceramide synthase inhibitor, and CERS5 knockdown prevented ceramide accumulation, JNK activation, and apoptosis in response to palmitate (P < 0.05). Exendin-4 also prevented the activation of the ceramide biosynthesis and JNK in response to palmitate, inhibiting apoptosis (P < 0.05).
Conclusions: Excess palmitate results in activation of ceramide biosynthesis, JNK signaling, and apoptosis in human CPCs. GLP1R activation counteracts this lipotoxic damage via inhibition of ceramide generation, and this may represent a cardioprotective mechanism.
Full text links
Related Resources
Trending Papers
Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.Endocrine Reviews 2024 April 28
The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association.Circulation 2024 April 26
Intravenous infusion of dexmedetomidine during the surgery to prevent postoperative delirium and postoperative cognitive dysfunction undergoing non-cardiac surgery: a meta-analysis of randomized controlled trials.European Journal of Medical Research 2024 April 19
Interstitial Lung Disease: A Review.JAMA 2024 April 23
Ventilator Waveforms May Give Clues to Expiratory Muscle Activity.American Journal of Respiratory and Critical Care Medicine 2024 April 25
Acute Kidney Injury and Electrolyte Imbalances Caused by Dapagliflozin Short-Term Use.Pharmaceuticals 2024 March 27
Systemic lupus erythematosus.Lancet 2024 April 18
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app