Use this url to cite publication: https://hdl.handle.net/20.500.12512/22977
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Hyperactivity in adrenergic signalling via alpha2A receptors contributes to human type 2 diabetes / A. Rosengren, R. Jokubka, D. Tojjar, C. Granhall, J. Tuncel, L. Eliasson, P. Rorsman, A. Salehi, L. Groop, V. Lyssenko, H. Luthman, E. Renström
Type of publication
Tezės Web of Science duomenų bazėje / Theses in Web of Science database (T1a1)
Author(s)
Rosengren, Anders | Lund University Diabetes Centre, Malmo, Sweden |
Lund University Diabetes Centre, Malmö, Sweden | |
Tojjar, Damon | Lund University Diabetes Centre, Malmö, Sweden |
Granhall, Charlotte | Lund University Diabetes Centre, Malmö, Sweden |
Tuncel, Jonatan | Lund University Diabetes Centre, Malmö, Sweden |
Eliasson, Lena | Lund University Diabetes Centre, Malmö, Sweden |
Rorsman, Patrik | Lund University Diabetes Centre, Malmö, Sweden |
Salehi, Albert S. | Lund University Diabetes Centre, Malmö, Sweden |
Groop, Leif | Lund University Diabetes Centre, Malmö, Sweden |
Lyssenko, Valeriya | Lund University Diabetes Centre, Malmö, Sweden |
Luthman, Holger | Lund University Diabetes Centre, Malmö, Sweden |
Renström, Erik | Lund University Diabetes Centre, Malmö, Sweden |
Title
Hyperactivity in adrenergic signalling via alpha2A receptors contributes to human type 2 diabetes / A. Rosengren, R. Jokubka, D. Tojjar, C. Granhall, J. Tuncel, L. Eliasson, P. Rorsman, A. Salehi, L. Groop, V. Lyssenko, H. Luthman, E. Renström
Publisher (trusted)
European Health Management Association Ltd |
Date Issued
Date Issued |
---|
2009-09-02 |
Extent
p. S50-S50, no. 108.
Is part of
Diabetologia : 45th Annual Meeting of the European-Association-for-the-Study-of-Diabetes : September 30-October 02, 2009, Vienna, Austria. Berlin ; Heidelberg : Springer, 2009, vol. 52, iss. 1, suppl., September.
Version
Originalus / Original
Series/Report no.
Diabetologia.
Field of Science
Abstract
Background and aims: Sequence variations in several genes have been demonstrated to contribute to the strong heredity of type 2-diabetes (T2D), but the exact pathogenic mechanisms remain largely unknown. Here we undertake a translational approach to couple genetic variations to detailed mechanistic studies. Materials and methods: The GK rat is a model of T2D that harbours naturally occurring genetic variations that predispose to hyperglycemia. The major diabetes susceptibility locus in the GK rat, the Niddm1 locus, is homologous to an important diabetes locus on human chromosome 10. Through repeated back-crossing of the GK rat with normoglycemic F344 rats we established congenic strains harbouring small segments of GK-derived Niddm1. These rats were investigated by insulin release measurements, high-resolution single- cell capacitance measurements of exocytosis, gene expression studies, and pharmacological and RNAi-mediated rescue experiments. 6000 individuals from the Botnia Study well-characterized for insulin secretion were genotyped. We also measured insulin secretion from human pancreatic islets. Results: From investigations of congenic strains with different extent of GK genome we identified a 1.4 Mb locus within Niddm1 that confers impaired insulin secretion in vivo and in vitro through defective pancreatic β-cell exocytosis. This locus contains five genes, one of which is Adra2a that encodes the alpha2A-adrenergic receptor. Adra2a was overexpressed by 59% (P<0.01) on the mRNA level and by 100% (P<0.001) on the protein level in congenic rats exhibiting impaired insulin secretion. Adra2a mediates adrenergic suppression of insulin secretion. Pharmacological receptor antagonism with yohimbine or silencing of receptor expression both led to complete normalization of insulin secretion in congenic islets. Blockade of the down-stream effector (calcineurin) of Adra2a signalling rescued β-cell function. Importantly,[...].
Type of document
type::text::conference output::conference proceedings::conference paper
ISSN (of the container)
0012-186X
Other Identifier(s)
(LSMU ALMA)990000859740107106
Coverage Spatial
Austrija / Austria (AT)
Language
Anglų / English (en)
Journal | IF | AIF | AIF (min) | AIF (max) | Cat | AV | Year | Quartile |
---|---|---|---|---|---|---|---|---|
DIABETOLOGIA | 6.551 | 3.884 | 3.884 | 3.884 | 1 | 1.687 | 2009 | Q1 |
Journal | IF | AIF | AIF (min) | AIF (max) | Cat | AV | Year | Quartile |
---|---|---|---|---|---|---|---|---|
DIABETOLOGIA | 6.551 | 3.884 | 3.884 | 3.884 | 1 | 1.687 | 2009 | Q1 |