Proteomic analysis of conditioned media from glucose responsive and glucose nonresponsive phenotypes reveals a panel of secreted proteins associated with beta cell dysfunction


Dowling, Paul and Shields, William and Rani, Sweta and Meleady, Paula and Henry, Michael and Jeppesen, Per Bendix and O'Driscoll, Lorraine and Clynes, Martin (2008) Proteomic analysis of conditioned media from glucose responsive and glucose nonresponsive phenotypes reveals a panel of secreted proteins associated with beta cell dysfunction. Electrophoresis, 29 (20). pp. 4141-4149. ISSN 0173-0835

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Abstract

Media conditioned by dysfunctioning pancreatic beta cells offer an excellent source of potential protein markers associated with this phenotype. Proteins identified from cell culture model systems are often found to be of importance clinically. Previous work by us and others have shown that low-passage MIN-6 cells (MIN-6(L)) respond to changes in glucose concentrations, producing an approximately 5.5-fold glucose-stimulated insulin secretion (GSIS) in response to 26.7 mmol/L, compared with 3.3 mmol/L, glucose. After continuous culture or high-passage (MIN-(H)), this GSIS was no longer present and thus represents an excellent model system for investigating beta cell dysfunction. Employing 2-D difference gel electrophoresis and mass spectrometry a panel of protein markers were identified in conditioned media (CM) from MIN-6(L) and MIN-6(H) beta cells. These proteins, including secretogranin II, secretogranin III and transthyretin, are associated with secretory granule biogenesis and were found to have substantially increased levels in the CM from the non-responsive high-passage MIN-6 beta cells. A panel of protein markers found to have increased abundance levels in CM from MIN- 6(H) compared with MIN-6(L) beta cells may have the potential to be used clinically for assessing beta cell function and to monitor the effects of specific therapeutics.

Item Type: Article
Keywords: Beta cell; Biomarkers; Diabetes; Difference gel electrophoresis; MIN-6;
Academic Unit: Faculty of Science and Engineering > Biology
Item ID: 7352
Identification Number: 10.1002/elps.200800152
Depositing User: Paul Dowling
Date Deposited: 17 Aug 2016 15:50
Journal or Publication Title: Electrophoresis
Publisher: Wiley-VCH Verlag
Refereed: Yes
Funders: Higher Education Authority (HEA)
URI:

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