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Diabetologia
Article
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PubMed Central
Other literature type . 2009
License: CC BY NC
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Diabetologia
Article . 2009 . Peer-reviewed
Data sources: Crossref
Diabetologia
Article . 2010
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Evidence for neuroendocrine function of a unique splicing form of TCF7L2 in human brain, islets and gut

Authors: Prokunina-Olsson, L.; Hall, J. L.;

Evidence for neuroendocrine function of a unique splicing form of TCF7L2 in human brain, islets and gut

Abstract

Variants in the TCF7L2 gene remain the strongest genetic associations with increased risk of type 2 diabetes. Recently, we identified a unique splicing form of TCF7L2 expressed in pancreatic islets, pancreas and colon and detected by assay 'ex13-13b'. The expression of ex13-13b strongly correlated with proinsulin in glucose-stimulated pancreatic islets, suggesting a potential role for this form in the development of type 2 diabetes. The goal of this study was to further characterise this unique TCF7L2 splicing form in human tissues.We used a panel of 34 human tissues and 80 human cell lines to measure the expression of assay ex13-13b with use of quantitative RT-PCR.The highest expression of assay ex13-13b was detected in several areas of the brain (hypothalamus/thalamus, occipital lobe) and in neuronal cell line SHS5Y5. Low expression was confirmed in pancreatic islets, small intestine, pancreas and colon, while no expression was detected in other human tissues and cell lines. The expression of assay ex13-13b correlated with the gene for cocaine- and amphetamine-regulated transcript (CART, also known as CARTPT) in a panel of human tissues (n = 12, r = 0.85, p = 0.00046), pancreatic islets (n = 23, r = 0.62, p = 0.0016) and colon (n = 98, r = 0.54, p < 0.0001).The significant correlation between expression of a unique splicing form of TCF7L2, named here TCF7L2-NE, and CART, the gene for an anorexigenic neurohormone expressed in the central and peripheral nervous system, suggests that these transcripts may share neuroendocrine functions important for brain, gut and pancreatic islets.

Keywords

Colon, Reverse Transcriptase Polymerase Chain Reaction, Endocrinology, Diabetes and Metabolism, Short Communication, Brain, Genetic Variation, Cell Line, Alternative Splicing, Islets of Langerhans, Diabetes Mellitus, Type 2, Risk Factors, Intestine, Small, Mutation, Internal Medicine, Humans, TCF Transcription Factors, Pancreas, Transcription Factor 7-Like 2 Protein

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
22
Average
Top 10%
Top 10%
Green
hybrid