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)

Abrogation of adenosine A(1) receptor signalling improves metabolic regulation in mice by modulating oxidative stress and inflammatory responses

Article/chapterEnglish2015

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2015-04-03
Springer Science and Business Media LLC,2015
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LIBRIS-ID:oai:DiVA.org:uu-258321
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-258321URI
https://doi.org/10.1007/s00125-015-3570-3DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:131471533URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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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 and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
Insulin sensitivity and resistance
Islets
Metabolic physiology in vivo
Metabolic syndrome
Oxidative stress
Type 2 diabetes
Visceral adipose tissue

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Gao, XiangUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)gaoxi322 (author)
Sandberg, MonicaUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)mosan330 (author)
Zollbrecht, Christa (author)
Zhang, Xing-MeiKarolinska Institutet (author)
Hezel, Michael (author)
Liu, Ming (author)
Peleli, MariaKarolinska Institutet (author)
Lai, En-Yin (author)
Harris, Robert A.Karolinska Institutet (author)
Persson, Erik G.Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)erikpers (author)
Fredholm, Bertil B.Karolinska Institutet (author)
Jansson, LeifUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)leifjans (author)
Carlstrom, MattiasKarolinska Institutet (author)
Uppsala universitetInstitutionen för medicinsk cellbiologi (creator_code:org_t)

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In:Diabetologia: Springer Science and Business Media LLC58:7, s. 1610-16200012-186X1432-0428

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By the author/editor: Yang, Ting; Gao, Xiang; Sandberg, Monica; Zollbrecht, Chri ...; Zhang, Xing-Mei; Hezel, Michael; show more...; Liu, Ming; Peleli, Maria; Lai, En-Yin; Harris, Robert A ...; Persson, Erik G.; Fredholm, Bertil ...; Jansson, Leif; Carlstrom, Matti ...; show less...

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