Source:http://linkedlifedata.com/resource/pubmed/id/21536682
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
25
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| pubmed:dateCreated |
2011-6-20
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| pubmed:abstractText |
Increasing evidence suggests that endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of type 2 diabetes mellitus. SEL1L is an ER membrane protein that is highly expressed in the pancreatic islet and acinar cells. We have recently reported that a deficiency of SEL1L causes systemic ER stress and leads to embryonic lethality in mice. Here we show that mice with one functional allele of Sel1l (Sel1l(+/-)) are more susceptible to high fat diet (HFD)-induced hyperglycemia. Sel1l(+/-) mice have a markedly reduced ?-cell mass as a result of decreased ?-cell proliferation. Consequently, Sel1l(+/-) mice are severely glucose-intolerant and exhibit significantly retarded glucose-stimulated insulin secretion. Pancreatic islets from Sel1l(+/-) mice stimulated with a high concentration of glucose in vitro express significantly higher levels of unfolded protein response genes than those from wild-type control mice. Furthermore, dominant-negative interference of SEL1L function in insulinoma cell lines severely impairs, whereas overexpression of SEL1L efficiently improves protein secretion. Taken together, our results indicate that haploid insufficiency of SEL1L predispose mice to high fat diet-induced hyperglycemia. Our findings highlight a critical and previously unknown function for SEL1L in regulating adult ?-cell function and growth.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Dietary Fats,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sel1h protein, mouse
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
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| pubmed:issn |
1083-351X
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
24
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| pubmed:volume |
286
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
22275-82
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:21536682-Animals,
pubmed-meshheading:21536682-Cell Count,
pubmed-meshheading:21536682-Cell Proliferation,
pubmed-meshheading:21536682-Dietary Fats,
pubmed-meshheading:21536682-Endoplasmic Reticulum,
pubmed-meshheading:21536682-Gene Expression Regulation,
pubmed-meshheading:21536682-Genetic Predisposition to Disease,
pubmed-meshheading:21536682-Glucose,
pubmed-meshheading:21536682-Glucose Intolerance,
pubmed-meshheading:21536682-Haploinsufficiency,
pubmed-meshheading:21536682-Heterozygote,
pubmed-meshheading:21536682-Hyperglycemia,
pubmed-meshheading:21536682-Insulin,
pubmed-meshheading:21536682-Insulin-Secreting Cells,
pubmed-meshheading:21536682-Liver,
pubmed-meshheading:21536682-Male,
pubmed-meshheading:21536682-Mice,
pubmed-meshheading:21536682-Mice, Inbred C57BL,
pubmed-meshheading:21536682-Obesity,
pubmed-meshheading:21536682-Protein Unfolding,
pubmed-meshheading:21536682-Proteins
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| pubmed:year |
2011
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| pubmed:articleTitle |
Haploid insufficiency of suppressor enhancer Lin12 1-like (SEL1L) protein predisposes mice to high fat diet-induced hyperglycemia.
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| pubmed:affiliation |
Department of Animal Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York 14850, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|