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Abrogation of adeno...
Abrogation of adenosine A(1) receptor signalling improves metabolic regulation in mice by modulating oxidative stress and inflammatory responses
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Yang, Ting (author)
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- Gao, Xiang (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Sandberg, Monica (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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Zollbrecht, Christa (author)
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- Zhang, Xing-Mei (author)
- Karolinska Institutet
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Hezel, Michael (author)
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Liu, Ming (author)
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- Peleli, Maria (author)
- Karolinska Institutet
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Lai, En-Yin (author)
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- Harris, Robert A. (author)
- Karolinska Institutet
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- Persson, Erik G. (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Fredholm, Bertil B. (author)
- Karolinska Institutet
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- Jansson, Leif (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Carlstrom, Mattias (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2015-04-03
- 2015
- English.
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 58:7, s. 1610-1620
- Related links:
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https://link.springe...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Aims/hypothesis Adenosine is an important regulator of metabolism; however, the role of the A(1) receptor during ageing and obesity is unclear. The aim of this study was to investigate the effects of A(1) signalling in modulating metabolic function during ageing. Methods Age-matched young and aged A (1) (also known as Adora1)-knockout (A (1) (-/-)) and wild-type (A (1) (+/+)) mice were used. Metabolic regulation was evaluated by body composition, and glucose and insulin tolerance tests. Isolated islets and islet arterioles were used to detect islet endocrine and vascular function. Oxidative stress and inflammation status were measured in metabolic organs and systemically. Results Advanced age was associated with both reduced glucose clearance and insulin sensitivity, as well as increased visceral adipose tissue (VAT) in A (1) (+/+) compared with A (1) (-/-) mice. Islet morphology and insulin content were similar between genotypes, but relative changes in in vitro insulin release following glucose stimulation were reduced in aged A (1) (+/+) compared with A (1) (-/-) mice. Islet arteriolar responses to angiotensin II were stronger in aged A (1) (+/+) mice, this being associated with increased NADPH oxidase activity. Ageing resulted in multiple changes in A (1) (+/+) compared with A (1) (-/-) mice, including enhanced NADPH oxidase-derived O-2 (-) formation and NADPH oxidase isoform 2 (Nox2) protein expression in pancreas and VAT; elevated levels of circulating insulin, leptin and proinflammatory cytokines (TNF-alpha, IL-1 beta, IL-6 and IL-12); and accumulation of CD4(+) T cells in VAT. This was associated with impaired insulin signalling in VAT from aged A (1) (+/+) mice. Conclusions/interpretation These studies emphasise that A(1) receptors regulate metabolism and islet endocrine and vascular functions during ageing, including via the modulation of oxidative stress and inflammatory responses, among other things.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Insulin sensitivity and resistance
- Islets
- Metabolic physiology in vivo
- Metabolic syndrome
- Oxidative stress
- Type 2 diabetes
- Visceral adipose tissue
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Yang, Ting
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Gao, Xiang
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Sandberg, Monica
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Zollbrecht, Chri ...
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Zhang, Xing-Mei
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Hezel, Michael
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show more...
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Liu, Ming
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Peleli, Maria
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Lai, En-Yin
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Harris, Robert A ...
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Persson, Erik G.
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Fredholm, Bertil ...
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Jansson, Leif
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Carlstrom, Matti ...
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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 Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Diabetologia
- By the university
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Uppsala University
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Karolinska Institutet