| Ceramide formation as a target in beta-cell survival and function. | |
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MedLine Citation:
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PMID: 21635197 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Introduction: Ceramide may be synthesized de novo or generated by sphingomyelinase-dependent hydrolysis of sphingomyelin. Areas covered: The role of ceramide, ceramide-sensitive signaling and ion channels in β-cell apoptosis, lipotoxicity and amyloid-induced β-cell death. Expert opinion: Ceramide participates in β-cell dysfunction and apoptosis after exposure to TNFα, IL-1β and IFN-γ, excessive amyloid and islet amyloid polypeptide or non-esterified fatty acids (lipotoxicity). Knockout of sphingomyelin synthase 1, which converts ceramide to sphingomyelin, leads to impairment of insulin secretion. Increased ceramidase activity or pharmacological inhibition of ceramide synthetase, inhibits β-cell apoptosis. Ceramide contributes to endoplasmatic reticulum (ER) stress, decreased mitochondrial membrane potential in insulin-secreting cells and mitochondrial release of cytochrome c into the cytosol, which are all triggers of apoptotic cell death. Ceramide-dependent signaling involves activation of extracellularly regulated kinases 1 and 2 (ERK1/2), downregulation of Period (Per)-aryl hydrocarbon receptor nuclear translocator (Arnt)-single-minded (Sim) kinase (PASK), activation of okadaic-acid-sensitive protein phosphatase 2A (PP2A) and stimulation of NADPH-oxidase with generation of superoxides and lipid peroxides. Ceramide reduces the activity of voltage gated potassium (Kv)-channels in insulin-secreting cells. The role of ceramide in β-cell survival and function may be therapeutically relevant, because ceramide formation can be suppressed by pharmacological inhibition of ceramide synthetase and/or sphingomyelinase. |
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Authors:
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Florian Lang; Susanne Ullrich; Erich Gulbins |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-2 |
Journal Detail:
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Title: Expert opinion on therapeutic targets Volume: - ISSN: 1744-7631 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101127833 Medline TA: Expert Opin Ther Targets Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Tübingen, Institute of Physiology , Gmelinstrasse 5, D-72076 Tübingen , Germany +49 7071 29 72194 ; +49 7071 29 5618 ; florian.lang@uni-tuebingen.de. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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