A1 receptor deficiency causes increased insulin and glucagon secretion in mice

Biochem Pharmacol. 2007 Dec 3;74(11):1628-35. doi: 10.1016/j.bcp.2007.08.006. Epub 2007 Aug 9.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Deoxyglucose / administration & dosage
  • Deoxyglucose / metabolism
  • Deoxyglucose / pharmacokinetics
  • Female
  • Genotype
  • Glucagon / blood
  • Glucagon / metabolism*
  • Glucose / administration & dosage
  • Glucose / metabolism
  • Glucose / pharmacokinetics
  • Glucose Tolerance Test
  • Glycated Hemoglobin A / metabolism
  • In Vitro Techniques
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin / pharmacology
  • Insulin Secretion
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Muscle Contraction / drug effects
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Adenosine A1 / deficiency*
  • Receptor, Adenosine A1 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • RNA, Messenger
  • Receptor, Adenosine A1
  • hemoglobin A1c protein, human
  • Glucagon
  • Deoxyglucose
  • Glucose