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The diabetes suscep...
The diabetes susceptibility gene clec16a regulates mitophagy.
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Soleimanpour, Scott A (author)
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Gupta, Aditi (author)
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Bakay, Marina (author)
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Ferrari, Alana M (author)
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Groff, David N (author)
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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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Spruce, Lynn A (author)
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Kushner, Jake A (author)
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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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Seeholzer, Steven H (author)
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Kaufman, Brett A (author)
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Hakonarson, Hakon (author)
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Stoffers, Doris A (author)
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(creator_code:org_t)
- Elsevier BV, 2014
- 2014
- English.
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In: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 157:7, s. 1577-1590
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://doi.org/10.1...
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Abstract
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- Clec16a has been identified as a disease susceptibility gene for type 1 diabetes, multiple sclerosis, and adrenal dysfunction, but its function is unknown. Here we report that Clec16a is a membrane-associated endosomal protein that interacts with E3 ubiquitin ligase Nrdp1. Loss of Clec16a leads to an increase in the Nrdp1 target Parkin, a master regulator of mitophagy. Islets from mice with pancreas-specific deletion of Clec16a have abnormal mitochondria with reduced oxygen consumption and ATP concentration, both of which are required for normal β cell function. Indeed, pancreatic Clec16a is required for normal glucose-stimulated insulin release. Moreover, patients harboring a diabetogenic SNP in the Clec16a gene have reduced islet Clec16a expression and reduced insulin secretion. Thus, Clec16a controls β cell function and prevents diabetes by controlling mitophagy. This pathway could be targeted for prevention and control of diabetes and may extend to the pathogenesis of other Clec16a- and Parkin-associated diseases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- art (subject category)
- ref (subject category)
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Cell
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- By the author/editor
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Soleimanpour, Sc ...
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Gupta, Aditi
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Bakay, Marina
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Ferrari, Alana M
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Groff, David N
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Fadista, Joao
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show more...
-
Spruce, Lynn A
-
Kushner, Jake A
-
Groop, Leif
-
Seeholzer, Steve ...
-
Kaufman, Brett A
-
Hakonarson, Hako ...
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Stoffers, Doris ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Cell
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Lund University