A1 receptor deficiency causes increased insulin and glucagon secretion in mice.
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.
Johansson
Stina M
SM
Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden. Stina.M.Johansson@ki.se
Salehi
Albert
A
Sandström
Marie E
ME
Westerblad
Håkan
H
Lundquist
Ingmar
I
Carlsson
Per-Ola
PO
Fredholm
Bertil B
BB
Katz
Abram
A
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003847:Deoxyglucose / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D005838:Genotype; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000172:deficiency* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D001786:Blood Glucose; D003847:Deoxyglucose; D005934:Glucagon; D005947:Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; C517652:hemoglobin A1c protein, human