ArticleDiabetologia2012
The ghrelin gene products and exendin-4 promote survival of human pancreatic islet endothelial cells in hyperglycaemic conditions, through phosphoinositide 3-kinase/Akt, extracellular signal-related kinase (ERK)1/2 and cAMP/protein kinase A (PKA) signalling pathways.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Obestatin: canonical and unexpected functions.Reviews in endocrine & metabolic disorders · 2026Review
- Could Ghrelin Expression Regulate Diastolic Cardiac Function in Type 2 Diabetic Obese Patients?Diabetes/metabolism research and reviews · 2025Observational
- Research Progress of Bioactive Peptides in Improving Type II Diabetes.Foods (Basel, Switzerland) · 2025Review
- Polyethylene glycol loxenatide protects diabetic kidneys by inhibiting GRP78/PERK/eIF2α pathway, and improves cardiac injury by suppressing TLR4/NF-κB inflammatory pathway.BMC cardiovascular disorders · 2024Article
- The Importance of Intra-Islet Communication in the Function and Plasticity of the Islets of Langerhans during Health and Diabetes.International journal of molecular sciences · 2024Review
- Beta-Cell Tipe1 Orchestrates Insulin Secretion and Cell Proliferation by Promoting Gαs/cAMP Signaling via USP5.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- Ghrelin attenuates methylmercury-induced oxidative stress in neuronal cells.Molecular neurobiology · 2022Article
- Diverse and Complementary Effects of Ghrelin and Obestatin.Biomolecules · 2022Review
- A structure-specific small molecule inhibits a miRNA-200 family member precursor and reverses a type 2 diabetes phenotype.Cell chemical biology · 2022Article
- Ghrelin mediated regulation of neurosynaptic transmitters in depressive disorders.Current research in pharmacology and drug discovery · 2022Review
- Pleiotropic and Potentially Beneficial Effects of Reactive Oxygen Species on the Intracellular Signaling Pathways in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2021Review
- Glucagon-like peptide-1 receptor agonist reduces di(2-ethylhexyl) phthalate-induced atherosclerotic processes in vascular smooth muscle cells.Physiological research · 2020Article
- Forkhead box M1 inhibits endothelial cell apoptosis and cell-cycle arrest through ROS generation.International journal of clinical and experimental pathology · 2018Article
- Long-term treatment with the ghrelin receptor antagonist [d-Lys3]-GHRP-6 does not improve glucose homeostasis in nonobese diabetic MKR mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- 5-fluorouracil causes endothelial cell senescence: potential protective role of glucagon-like peptide 1.British journal of pharmacology · 2017Article
- Cinnamomum osmophloeum Kanehira ethanol extracts prevents human liver-derived HepG2 cell death from oxidation stress by induction of ghrelin gene expression.Journal of biosciences · 2017Article
- Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus.Scientific reports · 2017Article
- Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes.British journal of pharmacology · 2016Review
- SP6616 as a new Kv2.1 channel inhibitor efficiently promotes β-cell survival involving both PKC/Erk1/2 and CaM/PI3K/Akt signaling pathways.Cell death & disease · 2016Article
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Abstract
aims/hypothesisPancreatic islet microendothelium exhibits unique features in interdependent relationship with beta cells. Gastrointestinal products of the ghrelin gene, acylated ghrelin (AG), unacylated ghrelin (UAG) and obestatin (Ob), and the incretin, glucagon-like peptide-1 (GLP-1), prevent apoptosis of pancreatic beta cells. We investigated whether the ghrelin gene products and the GLP-1 receptor agonist exendin-4 (Ex-4) display survival effects in human pancreatic islet microendothelial cells (MECs) exposed to chronic hyperglycaemia.
methodsIslet MECs were cultured in high glucose concentration and treated with AG, UAG, Ob or Ex-4. Apoptosis was assessed by DNA fragmentation, Hoechst staining of the nuclei and caspase-3 activity. Western blot analyses and pharmacological inhibition of protein kinase B (Akt) and extracellular signal-related kinase (ERK)1/2 pathways, detection of intracellular cAMP levels and blockade of adenylyl cyclase (AC)/cAMP/protein kinase A (PKA) signalling were performed. Levels of NO, IL-1β and vascular endothelial growth factor (VEGF)-A in cell culture supernatant fractions were measured.
resultsIslet MECs express the ghrelin receptor GHS-R1A as well as GLP-1R. Treatment with AG, UAG, Ob and Ex-4 promoted cell survival and significantly inhibited glucose-induced apoptosis, through activation of PI3K/Akt, ERK1/2 phosphorylation and intracellular cAMP increase. Moreover, peptides upregulated B cell lymphoma 2 (BCL-2) and downregulated BCL-2-associated X protein (BAX) and CD40 ligand (CD40L) production, and significantly reduced the secretion of NO, IL-1β and VEGF-A. CONCLUSIONS/
interpretationThe ghrelin gene-derived peptides and Ex-4 exert cytoprotective effects in islet MECs. The anti-apoptotic effects involve phosphoinositide 3-kinase (PI3K)/Akt, ERK1/2 and cAMP/PKA pathways. These peptides could therefore represent a potential tool to improve islet vascularisation and, indirectly, islet cell function.
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