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Beta-cell specific ...
Beta-cell specific deletion of dicer1 leads to defective insulin secretion and diabetes mellitus
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- Kalis, Martins (author)
- Lund University,Lunds universitet,Diabetes - immunovirologi,Forskargrupper vid Lunds universitet,Diabetes - Immunovirology,Lund University Research Groups
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- Bolmeson, Caroline (author)
- Lund University,Lunds universitet,Create Health,Annan verksamhet, LTH,Lunds Tekniska Högskola,Evolutionär ekologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Other operations, LTH,Faculty of Engineering, LTH,Evolutionary ecology,Department of Biology,Faculty of Science
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- Esguerra, Jonathan (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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Gupta, Shashank (author)
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- Edlund, Anna (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Tormo-Badia, Neivis (author)
- Lund University,Lunds universitet,Diabetes - immunovirologi,Forskargrupper vid Lunds universitet,Diabetes - Immunovirology,Lund University Research Groups
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Speidel, Dina (author)
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- Holmberg, Dan (author)
- Umeå universitet,Medicinsk och klinisk genetik
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- Mayans, Sofia, 1973- (author)
- Umeå universitet,Immunologi/immunkemi,Sofia Mayans
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Khoo, Nelson KS (author)
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- Wendt, Anna (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Eliasson, Lena (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Cilio, Corrado (author)
- Lund University,Lunds universitet,Diabetes - immunovirologi,Forskargrupper vid Lunds universitet,Diabetes - Immunovirology,Lund University Research Groups
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Holmberg, Daniel (author)
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(creator_code:org_t)
- 2011-12-27
- 2011
- English.
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:12, s. e29166-
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Abstract
Subject headings
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- Mature microRNAs (miRNAs), derived through cleavage of pre-miRNAs by the Dicer1 enzyme, regulate protein expression in many cell-types including cells in the pancreatic islets of Langerhans. To investigate the importance of miRNAs in mouse insulin secreting beta-cells, we have generated mice with a beta-cells specific disruption of the Dicer1 gene using the Cre-lox system controlled by the rat insulin promoter (RIP). In contrast to their normoglycaemic control littermates (RIP-Cre(+/-) Dicer1(Delta/wt)), RIP-Cre(+/-) Dicer1(flox/flox) mice (RIP-Cre Dicer1(Delta/Delta)) developed progressive hyperglycaemia and full-blown diabetes mellitus in adulthood that recapitulated the natural history of the spontaneous disease in mice. Reduced insulin gene expression and concomitant reduced insulin secretion preceded the hyperglycaemic state and diabetes development. Immunohistochemical, flow cytometric and ultrastructural analyses revealed altered islet morphology, marked decreased beta-cell mass, reduced numbers of granules within the beta-cells and reduced granule docking in adult RIP-Cre Dicer1(Delta/Delta) mice. beta-cell specific Dicer1 deletion did not appear to disrupt fetal and neonatal beta-cell development as 2-week old RIP-Cre Dicer1(Delta/Delta) mice showed ultrastructurally normal beta-cells and intact insulin secretion. In conclusion, we have demonstrated that a beta-cell specific disruption of the miRNAs network, although allowing for apparently normal beta-cell development, leads to progressive impairment of insulin secretion, glucose homeostasis and diabetes development.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- gene-expression; microrna expression; mouse development; pancreas; differentiation; quantification; identification; dysfunction; pathway; driven
Publication and Content Type
- ref (subject category)
- art (subject category)
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Kalis, Martins
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Bolmeson, Caroli ...
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Esguerra, Jonath ...
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Gupta, Shashank
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Edlund, Anna
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Tormo-Badia, Nei ...
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show more...
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Speidel, Dina
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Holmberg, Dan
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Mayans, Sofia, 1 ...
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Khoo, Nelson KS
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Wendt, Anna
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Eliasson, Lena
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Cilio, Corrado
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Holmberg, Daniel
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Umeå University
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