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Defects in β-cell C...
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Li, LSKarolinska Institutet
(författare)
Defects in β-cell Ca2+ dynamics in age-induced diabetes
- Artikel/kapitelEngelska2014
Förlag, utgivningsår, omfång ...
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2014-11-13
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American Diabetes Association,2014
Nummerbeteckningar
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:130139967
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http://kipublications.ki.se/Default.aspx?queryparsed=id:130139967URI
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https://doi.org/10.2337/db13-1855DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Little is known about the molecular mechanisms underlying age-dependent deterioration in β-cell function. We now demonstrate that age-dependent impairment in insulin release, and thereby glucose homeostasis, is associated with subtle changes in Ca2+ dynamics in mouse β-cells. We show that these changes are likely to be accounted for by impaired mitochondrial function and to involve phospholipase C/inositol 1,4,5-trisphosphate–mediated Ca2+ mobilization from intracellular stores as well as decreased β-cell Ca2+ influx over the plasma membrane. We use three mouse models, namely, a premature aging phenotype, a mature aging phenotype, and an aging-resistant phenotype. Premature aging is studied in a genetically modified mouse model with an age-dependent accumulation of mitochondrial DNA mutations. Mature aging is studied in the C57BL/6 mouse, whereas the 129 mouse represents a model that is more resistant to age-induced deterioration. Our data suggest that aging is associated with a progressive decline in β-cell mitochondrial function that negatively impacts on the fine tuning of Ca2+ dynamics. This is conceptually important since it emphasizes that even relatively modest changes in β-cell signal transduction over time lead to compromised insulin release and a diabetic phenotype.
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Trifunovic, A
(författare)
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Kohler, MKarolinska Institutet
(författare)
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Wang, YXKarolinska Institutet
(författare)
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Berglund, JP
(författare)
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Illies, CKarolinska Institutet
(författare)
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Juntti-Berggren, LKarolinska Institutet
(författare)
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Larsson, NGKarolinska Institutet
(författare)
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Berggren, POKarolinska Institutet
(författare)
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Karolinska Institutet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Diabetes: American Diabetes Association63:12, s. 4100-41141939-327X0012-1797
Internetlänk
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Diabetes
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