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Sustained Beta-Cell...
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Drott, Carl JohanUppsala universitet,Institutionen för medicinsk cellbiologi
(författare)
Sustained Beta-Cell Dysfunction but Normalized Islet Mass in Aged Thrombospondin-1 Deficient Mice
- Artikel/kapitelEngelska2012
Förlag, utgivningsår, omfång ...
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2012-10-19
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Public Library of Science (PLoS),2012
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-185499
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-185499URI
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https://doi.org/10.1371/journal.pone.0047451DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1), that showed to be of importance for islet angiogenesis and beta-cell function in young mice. The present study aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. Islet and beta-cell mass were observed increased at 10-12 weeks of age in TSP-1 deficient mice, but were normalized before 16 weeks of age when compared to wild-type controls. Islet vascularity was normal in 10-12 and 16-week-old TSP-1 deficient animals, whereas islets of one-year-old animals lacking TSP-1 were hypervascular. Beta-cell dysfunction in TSP-1 deficient animals was present at similar magnitudes between 10-12 and 52 weeks of age, as evaluated by glucose tolerance tests. The insulin secretion capacity in vivo of islets in one-year-old TSP-1 deficient animals was only similar to 15% of that in wild-type animals. Using a transplantation model, we reconstituted TSP-1 in adult TSP-deficient islets. In contrast to neonatal TSP-1 deficient islets that we previously reported to regain function after TSP-1 reconstitution, adult islets failed to recover. We conclude that TSP-1 deficiency in islets causes changing vascular and endocrine morphological alterations postnatally, but is coupled to a chronic beta-cell dysfunction. The beta-cell dysfunction induced by TSP-1 deficiency is irreversible if not substituted early in life.
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Olerud, JohanUppsala universitet,Klinisk immunologi,Korsgren(Swepub:uu)joole425
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Emanuelsson, HannaUppsala universitet,Molekylär och morfologisk patologi,Pontén(Swepub:uu)hanem153
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Christoffersson, GustavUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)guchr179
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Carlsson, Per-OlaUppsala universitet,Institutionen för medicinsk cellbiologi,Endokrin diabetes och metabolism(Swepub:uu)perocarl
(författare)
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Uppsala universitetInstitutionen för medicinsk cellbiologi
(creator_code:org_t)
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Ingår i:PLOS ONE: Public Library of Science (PLoS)7:10, s. e47451-1932-6203
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