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TCF7L2 is a master ...
TCF7L2 is a master regulator of insulin production and processing
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- Zhou, Yuedan (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Park, Soo-Young (author)
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Su, Jing (author)
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Bailey, Kathleen (author)
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- Ottosson Laakso, Emilia (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Shcherbina, Liliya (author)
- Lund University,Lunds universitet,Neuroendokrin cellbiologi,Forskargrupper vid Lunds universitet,Neuroendocrine Cell Biology,Lund University Research Groups
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- Oskolkov, Nikolay (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Zhang, Enming (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Thevenin, Thomas (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Fadista, Joao (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Bennet, Hedvig (author)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups
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- Vikman, Petter (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Wierup, Nils (author)
- Lund University,Lunds universitet,Neuroendokrin cellbiologi,Forskargrupper vid Lunds universitet,Neuroendocrine Cell Biology,Lund University Research Groups
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- Fex, Malin (author)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups
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- Rung, Johan (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Rudbeck Lab
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- Wollheim, Claes (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Nobrega, Marcelo (author)
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- Renström, Erik (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Groop, Leif (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Hansson, Ola (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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(creator_code:org_t)
- 2014-07-11
- 2014
- English.
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6419-6431
- Related links:
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https://doi.org/10.1...
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Genome-wide association studies have revealed > 60 loci associated with type 2 diabetes ( T2D), but the underlying causal variants and functional mechanisms remain largely elusive. Although variants in TCF7L2 confer the strongest risk of T2D among common variants by presumed effects on islet function, the molecular mechanisms are not yet well understood. Using RNA-sequencing, we have identified a TCF7L2-regulated transcriptional network responsible for its effect on insulin secretion in rodent and human pancreatic islets. ISL1 is a primary target of TCF7L2 and regulates proinsulin production and processing via MAFA, PDX1, NKX6.1, PCSK1, PCSK2 and SLC30A8, thereby providing evidence for a coordinated regulation of insulin production and processing. The risk T-allele of rs7903146 was associated with increased TCF7L2 expression, and decreased insulin content and secretion. Using gene expression profiles of 66 human pancreatic islets donors', we also show that the identified TCF7L2-ISL1 transcriptional network is regulated in a genotype-dependent manner. Taken together, these results demonstrate that not only synthesis of proinsulin is regulated by TCF7L2 but also processing and possibly clearance of proinsulin and insulin. These multiple targets in key pathways may explain why TCF7L2 has emerged as the gene showing one of the strongest associations with T2D.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Zhou, Yuedan
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Park, Soo-Young
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Su, Jing
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Bailey, Kathleen
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Ottosson Laakso, ...
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Shcherbina, Lili ...
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show more...
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Oskolkov, Nikola ...
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Zhang, Enming
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Thevenin, Thomas
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Fadista, Joao
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Bennet, Hedvig
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Vikman, Petter
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Wierup, Nils
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Fex, Malin
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Rung, Johan
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Wollheim, Claes
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Nobrega, Marcelo
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Renström, Erik
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Groop, Leif
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Hansson, Ola
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Human Molecular ...
- By the university
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Uppsala University
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Lund University