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The R6/2 transgenic...
The R6/2 transgenic mouse model of Huntington's disease develops diabetes due to deficient {beta}-cell mass and exocytosis.
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- Björkqvist, Maria (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Translationell neuroendokrinologi,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Translational Neuroendocrinology,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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- Renström, Erik (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Wierup, Nils (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Petersén, Åsa (author)
- Lund University,Lunds universitet,Translationell neuroendokrinologi,Forskargrupper vid Lunds universitet,Translational Neuroendocrinology,Lund University Research Groups
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- Gil, Joana (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Bacos, Karl (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Popovic, Natalija (author)
- Lund University,Lunds universitet,Basala gangliernas patofysiologi,Forskargrupper vid Lunds universitet,Basal Ganglia Pathophysiology,Lund University Research Groups
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- Li, Jia-Yi (author)
- Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups
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- Sundler, Frank (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Brundin, Patrik (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Mulder, Hindrik (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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(creator_code:org_t)
- 2005-01-13
- 2005
- English.
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 14:5, s. 565-574
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Abstract
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- Diabetes frequently develops in Huntington's disease (HD) patients and in transgenic mouse models of HD such as the R6/2 mouse. The underlying mechanisms have not been clarified. Elucidating the pathogenesis of diabetes in HD would improve our understanding of the molecular mechanisms involved in HD neuropathology. With this aim, we examined our colony of R6/2 mice with respect to glucose homeostasis and islet function. At week 12, corresponding to end-stage HD, R6/2 mice were hyperglycemic and hypoinsulinemic and failed to release insulin in an intravenous glucose tolerance test. In vitro, basal and glucose-stimulated insulin secretion was markedly reduced. Islet nuclear huntingtin inclusions increased dramatically over time, predominantly in ß-cells. ß-cell mass failed to increase normally with age in R6/2 mice. Hence, at week 12, ß-cell mass and pancreatic insulin content in R6/2 mice were 35±5 and 16±3% of that in wild-type mice, respectively. The normally occurring replicating cells were largely absent in R6/2 islets, while no abnormal cell death could be detected. Single cell patch-clamp experiments revealed unaltered electrical activity in R6/2 ß-cells. However, exocytosis was virtually abolished in ß- but not in {alpha}-cells. The blunting of exocytosis could be attributed to a 96% reduction in the number of insulin-containing secretory vesicles. Thus, diabetes in R6/2 mice is caused by a combination of deficient ß-cell mass and disrupted exocytosis.
Subject headings
- 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
- art (subject category)
- ref (subject category)
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- By the author/editor
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Björkqvist, Mari ...
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Fex, Malin
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Renström, Erik
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Wierup, Nils
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Petersén, Åsa
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Gil, Joana
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show more...
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Bacos, Karl
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Popovic, Natalij ...
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Li, Jia-Yi
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Sundler, Frank
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Brundin, Patrik
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Mulder, Hindrik
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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 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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Lund University