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Albert Salehi

S Albert Salehi

Research team manager

Albert Salehi

A(1) receptor deficiency causes increased insulin and glucagon secretion in mice

Author

  • Stina M. Johansson
  • S Albert Salehi
  • Marie E. Sandstroem
  • Hakan Westerblad
  • Ingmar Lundquist
  • Per-Ola Carlsson
  • Bertil B. Fredholm
  • Abram Katz

Summary, in English

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 higherbasal 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. (c) 2007 Elsevier Inc. All rights reserved.

Department/s

  • Islet cell physiology

Publishing year

2007

Language

English

Pages

1628-1635

Publication/Series

Biochemical Pharmacology

Volume

74

Issue

11

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Keywords

  • A(1) receptor
  • glucose uptake
  • insulin sensitivity
  • islet hormone secretion
  • adenosine
  • metabolism

Status

Published

Research group

  • Islet cell physiology

ISBN/ISSN/Other

  • ISSN: 0006-2952