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A(1) receptor deficiency causes increased insulin and glucagon secretion in mice
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2007 (English)In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1873-2968, Vol. 74, no 11, 1628-1635 p.Article in journal (Refereed) Published
Abstract [en]

Adenosine influences metabolism and the adenosine receptor antagonist caffeine decreases the risk of type 2 diabetes. In this study the metabolic role of one adenosine receptor subtype, the adenosine A(1)R, was evaluated in mice lacking this receptor [A(1)R (-/-)]. The HbA1c levels and body weight were not significantly different between wild type [A(1)R (+/+)] and A(1)R (-/-) mice (3-4 months) fed normal lab chow. At rest, plasma levels of glucose, insulin and glucagon were similar in both genotypes. Following glucose injection, glucose tolerance was not appreciably altered in A(1)R (-/-) mice. Glucose injection induced sustained increases in plasma insulin and glucagon levels in A(1)R (-/-) mice, whereas A(1)R (+/+) control mice reacted with the expected transient increase in insulin and decrease in glucagon levels. Pancreas perfusion experiments showed that A(1)R (-/-) mice had a slightly higher basal insulin secretion than A(1)R (+/+) mice. The first phase insulin secretion (initiated with 16.7 mM glucose) was of the same magnitude in both genotypes, but the second phase was significantly enhanced in the A(1)R (-/-) pancreata compared with A(1)R (+/+). Insulin- and contraction-mediated glucose uptake in skeletal muscle were not significantly different between in A(1)R (-/-) and A(1)R (+/+) mice. All adenosine receptors were expressed at mRNA level in skeletal muscle in A(1)R (+/+) mice and the mRNA A(2A)R, A(2B)R and A(3)R levels were similar in A(1)R (-/-) and A(1)R (+/+) mice. In conclusion, the A(1)R minimally affects muscle glucose uptake, but is important in regulating pancreatic islet function.

Place, publisher, year, edition, pages
2007. Vol. 74, no 11, 1628-1635 p.
Keyword [en]
Adenosine, Metabolism, Islet hormone secretion, Insulin sensitivity, Glucose uptake, A1 receptor
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-11941DOI: 10.1016/j.bcp.2007.08.006ISI: 000251118600008PubMedID: 17869224OAI: oai:DiVA.org:uu-11941DiVA: diva2:39710
Available from: 2007-11-07 Created: 2007-11-07 Last updated: 2011-01-17Bibliographically approved

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Carlsson, Per-Ola

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