| Conditional expression of the FTO gene product in rat INS-1 cells reveals its rapid turnover and a role in the profile of glucose-induced insulin secretion. | |
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MedLine Citation:
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PMID: 21070190 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Common polymorphisms within the FTO (fat mass and obesity-associated) gene correlate with increased BMI (body mass index) and a rising risk of Type 2 diabetes. FTO is highly expressed in the brain but has also been detected in peripheral tissues, including the endocrine pancreas, although its function there is unclear. The aim of the present study was to investigate the role of FTO protein in pancreatic β-cells using a conditional expression system developed in INS-1 cells. INS-1 cells were stably transfected with FTO-HA (haemagluttinin) incorporated under the control of a tetracycline-inducible promoter. Induction of FTO protein resulted in localization of the tagged protein to the nucleus. The level of FTO-HA protein achieved in transfected cells was tightly regulated, and experiments with selective inhibitors revealed that FTO-HA is rapidly degraded via the ubiquitin/proteasome pathway. The nuclear localization was not altered by proteasome inhibitors, although following treatment with PYR-41, an inhibitor of ubiquitination, some of the protein adopted a perinuclear localization. Unexpectedly, modestly increased expression of FTO-HA selectively enhanced the first phase of insulin secretion when INS-1 monolayers or pseudoislets were stimulated with 20 mM glucose, whereas the second phase remained unchanged. The mechanism responsible for the potentiation of glucose-induced insulin secretion is unclear; however, further experiments revealed that it did not involve an increase in insulin biosynthesis or any changes in STAT3 (signal transducer and activator of transcription 3) expression. Taken together, these results suggest that the FTO protein may play a hitherto unrecognized role in the control of first-phase insulin secretion in pancreatic β-cells. |
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Authors:
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Mark A Russell; Noel G Morgan |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Clinical science (London, England : 1979) Volume: 120 ISSN: 1470-8736 ISO Abbreviation: Clin. Sci. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7905731 Medline TA: Clin Sci (Lond) Country: England |
Other Details:
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Languages: eng Pagination: 403-13 Citation Subset: IM |
Affiliation:
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*Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry (University of Plymouth), Plymouth, Devon PL6 8BU, U.K. |
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