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Desmoglein-2 is imp...
Desmoglein-2 is important for islet function and β-cell survival
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- Myo Min, Kay K (författare)
- University of South Australia
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- Rojas-Canales, Darling (författare)
- Flinders Medical Centre
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- Penko, Daniella (författare)
- Royal Adelaide Hospital,University of Adelaide
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- DeNichilo, Mark (författare)
- University of South Australia
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- Cockshell, Michaelia P (författare)
- University of South Australia
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- Ffrench, Charlie B (författare)
- University of South Australia
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- Thompson, Emma J (författare)
- University of South Australia
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- Asplund, Olof (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Drogemuller, Christopher J (författare)
- University of Adelaide,Royal Adelaide Hospital
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- Prasad, Rashmi B (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Groop, Leif (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Melanoma Genomics,Translational Muscle Research,Lund University Research Groups
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- Grey, Shane T (författare)
- Garvan Institute of Medical Research
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- Thomas, Helen E (författare)
- University of Melbourne,St. Vincent’s Institute of Medical Research
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- Loudovaris, Thomas (författare)
- University of Melbourne,St. Vincent’s Institute of Medical Research
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- Kay, Thomas W (författare)
- St. Vincent’s Institute of Medical Research,University of Melbourne
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- Mahoney, My G (författare)
- Thomas Jefferson University
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- Jessup, Claire F (författare)
- University of Adelaide,Flinders University
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- Coates, P Toby (författare)
- University of Adelaide,Royal Adelaide Hospital
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- Bonder, Claudine S (författare)
- University of Adelaide,University of South Australia
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(creator_code:org_t)
- 2022-10-29
- 2022
- Engelska.
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Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 13:10
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Type 1 diabetes is a complex disease characterized by the lack of endogenous insulin secreted from the pancreatic β-cells. Although β-cell targeted autoimmune processes and β-cell dysfunction are known to occur in type 1 diabetes, a complete understanding of the cell-to-cell interactions that support pancreatic function is still lacking. To characterize the pancreatic endocrine compartment, we studied pancreata from healthy adult donors and investigated a single cell surface adhesion molecule, desmoglein-2 (DSG2). Genetically-modified mice lacking Dsg2 were examined for islet cell mass, insulin production, responses to glucose, susceptibility to a streptozotocin-induced mouse model of hyperglycaemia, and ability to cure diabetes in a syngeneic transplantation model. Herein, we have identified DSG2 as a previously unrecognized adhesion molecule that supports β-cells. Furthermore, we reveal that DSG2 is within the top 10 percent of all genes expressed by human pancreatic islets and is expressed by the insulin-producing β-cells but not the somatostatin-producing δ-cells. In a Dsg2 loss-of-function mice (Dsg2lo/lo), we observed a significant reduction in the number of pancreatic islets and islet size, and consequently, there was less total insulin content per islet cluster. Dsg2lo/lo mice also exhibited a reduction in blood vessel barrier integrity, an increased incidence of streptozotocin-induced diabetes, and islets isolated from Dsg2lo/lo mice were more susceptible to cytokine-induced β-cell apoptosis. Following transplantation into diabetic mice, islets isolated from Dsg2lo/lo mice were less effective than their wildtype counterparts at curing diabetes. In vitro assays using the Beta-TC-6 murine β-cell line suggest that DSG2 supports the actin cytoskeleton as well as the release of cytokines and chemokines. Taken together, our study suggests that DSG2 is an under-appreciated regulator of β-cell function in pancreatic islets and that a better understanding of this adhesion molecule may provide new opportunities to combat type 1 diabetes.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Mice
- Humans
- Animals
- Diabetes Mellitus, Type 1/metabolism
- Diabetes Mellitus, Experimental/genetics
- Streptozocin
- Cell Survival
- Islets of Langerhans/metabolism
- Insulin/metabolism
- Desmogleins/metabolism
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Myo Min, Kay K
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Rojas-Canales, D ...
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Penko, Daniella
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DeNichilo, Mark
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Cockshell, Micha ...
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Ffrench, Charlie ...
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visa fler...
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Thompson, Emma J
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Asplund, Olof
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Drogemuller, Chr ...
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Prasad, Rashmi B
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Groop, Leif
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Grey, Shane T
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Thomas, Helen E
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Loudovaris, Thom ...
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Kay, Thomas W
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Mahoney, My G
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Jessup, Claire F
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Coates, P Toby
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Bonder, Claudine ...
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visa färre...
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