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

Johansson, Stina M.; Salehi, S Albert LU ; Sandstroem, Marie E.; Westerblad, Hakan; Lundquist, Ingmar LU ; Carlsson, Per-Ola; Fredholm, Bertil B. and Katz, Abram (2007) In Biochemical Pharmacology 74(11). p.1628-1635
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
A(1) receptor, glucose uptake, insulin sensitivity, islet hormone secretion, adenosine, metabolism
in
Biochemical Pharmacology
volume
74
issue
11
pages
1628 - 1635
publisher
Elsevier
external identifiers
  • wos:000251118600008
  • scopus:35349004692
ISSN
0006-2952
DOI
10.1016/j.bcp.2007.08.006
language
English
LU publication?
yes
id
2f418577-a0f6-4369-b3ae-11aa319fb791 (old id 969310)
date added to LUP
2008-01-29 14:28:00
date last changed
2017-10-22 03:38:03
@article{2f418577-a0f6-4369-b3ae-11aa319fb791,
  abstract     = {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.},
  author       = {Johansson, Stina M. and Salehi, S Albert and Sandstroem, Marie E. and Westerblad, Hakan and Lundquist, Ingmar and Carlsson, Per-Ola and Fredholm, Bertil B. and Katz, Abram},
  issn         = {0006-2952},
  keyword      = {A(1) receptor,glucose uptake,insulin sensitivity,islet hormone secretion,adenosine,metabolism},
  language     = {eng},
  number       = {11},
  pages        = {1628--1635},
  publisher    = {Elsevier},
  series       = {Biochemical Pharmacology},
  title        = {A(1) receptor deficiency causes increased insulin and glucagon secretion in mice},
  url          = {http://dx.doi.org/10.1016/j.bcp.2007.08.006},
  volume       = {74},
  year         = {2007},
}