ArticleDiabetes2009
Degradation of cAMP-responsive element-binding protein by the ubiquitin-proteasome pathway contributes to glucotoxicity in beta-cells and human pancreatic islets.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- The Molecular Mechanisms of Cuproptosis and Small-Molecule Drug Design in Diabetes Mellitus.Molecules (Basel, Switzerland) · 2024Review
- Targeting Protein Kinases to Protect Beta-Cell Function and Survival in Diabetes.International journal of molecular sciences · 2024Review
- Ubiquitination and Metabolic Disease.Advances in experimental medicine and biology · 2024Review
- Review
- Pharmacological inhibitors of β-cell dysfunction and death as therapeutics for diabetes.Frontiers in endocrinology · 2023Review
- Regulation of insulin secretion by the post-translational modifications.Frontiers in cell and developmental biology · 2023Review
- Convergent Molecular Pathways in Type 2 Diabetes Mellitus and Parkinson's Disease: Insights into Mechanisms and Pathological Consequences.Molecular neurobiology · 2022Review
- Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies.International journal of molecular sciences · 2021Review
- Metabolic impacts of cordycepin on hepatic proteomic expression in streptozotocin-induced type 1 diabetic mice.PloS one · 2021Article
- Methamphetamine induces cardiomyopathy by Sigmar1 inhibition-dependent impairment of mitochondrial dynamics and function.Communications biology · 2020Article
- The KDM Inhibitor GSKJ4 Triggers CREB Downregulation via a Protein Kinase A and Proteasome-Dependent Mechanism in Human Acute Myeloid Leukemia Cells.Frontiers in oncology · 2020Article
- Bridging the Gap Between Diabetes and Stroke in Search of High Clinical Relevance Therapeutic Targets.Neuromolecular medicine · 2019Review
- Friend and foe: β-cell CaMolecular metabolism · 2019Review
- Proteasome limits plasticity-related signaling to the nucleus in the hippocampus.Neuroscience letters · 2018Article
- Regulated Cell Death Seen through the Lens of Islet Transplantation.Cell transplantation · 2018Review
- O-GlcNAcylation of protein kinase A catalytic subunits enhances its activity: a mechanism linked to learning and memory deficits in Alzheimer's disease.Aging cell · 2016Article
- Activation of Melatonin Signaling Promotes β-Cell Survival and Function.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Differences in long-term memory stability and AmCREB level between forward and backward conditioned honeybees (Apis mellifera).Frontiers in behavioral neuroscience · 2015Article
- Phosphorylation and degradation of tomosyn-2 de-represses insulin secretion.The Journal of biological chemistry · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveIn type 2 diabetes, chronic hyperglycemia is detrimental to beta-cells, causing apoptosis and impaired insulin secretion. The transcription factor cAMP-responsive element-binding protein (CREB) is crucial for beta-cell survival and function. We investigated whether prolonged exposure of beta-cells to high glucose affects the functional integrity of CREB. RESEARCH DESIGN AND
methodsINS-1E cells and rat and human islets were used. Gene expression was analyzed by RT-PCR and Western blotting. Apoptosis was detected by cleaved caspase-3 emergence, DNA fragmentation, and electron microscopy.
resultsChronic exposure of INS-1E cells and rat and human islets to high glucose resulted in decreased CREB protein expression, phosphorylation, and transcriptional activity associated with apoptosis and impaired beta-cell function. High-glucose treatment increased CREB polyubiquitination, while treatment of INS-1E cells with the proteasome inhibitor MG-132 prevented the decrease in CREB content. The emergence of apoptosis in INS-1E cells with decreased CREB protein expression knocked down by small interfering RNA suggested that loss of CREB protein content induced by high glucose contributes to beta-cell apoptosis. Loading INS-1E cells or human islets with a cell-permeable peptide mimicking the proteasomal targeting sequence of CREB blocked CREB degradation and protected INS-1E cells and human islets from apoptosis induced by high glucose. The insulin secretion in response to glucose and the insulin content were preserved in human islets exposed to high glucose and loaded with the peptide.
conclusionsThese studies demonstrate that the CREB degradation by the ubiquitin-proteasome pathway contributes to beta-cell dysfunction and death upon glucotoxicity and provide new insight into the cellular mechanisms of glucotoxicity.
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Registered trials
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