Activation of the A1 adenosine receptor increases insulin-stimulated glucose transport in isolated rat soleus muscle

• Published in: Applied physiology, nutrition, and metabolism nutrition, and metabolism, 2007-08, Vol.32 (4), p.701-710
• Main Authors: Thong, Farah S.L, Lally, Jamie S.V, Dyck, David J, Greer, Felicia, Bonen, Arend, Graham, Terry E
• Format: Article
• Language: English
• Subjects: 1,3-dipropyl-8-cyclopentylxanthine; 3-O-Methylglucose - metabolism; Adenosine - administration & dosage; Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenosine - physiology; Adenosine A1 Receptor Antagonists; Animals; Biological Transport - drug effects; Biological Transport - physiology; Cell Membrane - metabolism; cyclopentyladenosine; cyclopentyladénosine; Dose-Response Relationship, Drug; Glucose - metabolism; Glucose Transporter Type 4 - metabolism; GLUT4 glucose transporters; In Vitro Techniques; Insulin - pharmacology; insulin sensitivity; Male; muscle squelettique; Muscle, Skeletal - metabolism; Rats; Rats, Wistar; Receptor, Adenosine A1 - genetics; Receptor, Adenosine A1 - metabolism; Receptor, Adenosine A1 - physiology; RNA, Messenger - metabolism; sensibilité à l'insuline; skeletal muscle; transporteurs du glucose GLUT4; Xanthines - administration & dosage; Xanthines - pharmacology
• ISSN: 1715-5312; 1715-5320
• DOI: 10.1139/H07-039

The A 1 adenosine receptor (A 1 AR) has been suggested to participate in insulin- and contraction-stimulated glucose transport in skeletal muscle, but the qualitative and quantitative nature of the effect are controversial. We sought to determine if A 1 AR is expressed in rat soleus muscle and then characterize its role in glucose transport in this muscle. A 1 AR mRNA and protein expression were determined by RT-PCR and Western blotting, respectively. To examine the role of adenosine in 3-O-methylglucose transport, isolated muscles were exposed to adenosine deaminase and α, β-methylene adenosine diphosphate to remove endogenous adenosine and were left unstimulated (basal) or stimulated with insulin. To assess the functional participation of A 1 AR in 3-O-methylglucose transport, muscles were incubated with A 1 -selective agonist and (or) antagonist in the absence of endogenous adenosine and with or without insulin. A 1 AR mRNA was expressed in soleus muscle and A 1 AR was present at the plasma membrane. Removal of endogenous adenosine reduced glucose transport in response to 100 μU/mL insulin (~50%). The A 1 -selective agonist, N 6 -cyclopentyladenosine, increased submaximal (100 μU/mL) insulin-stimulated glucose transport in a dose-dependent manner (0.001-1.0 μmol/L). This stimulatory effect was inhibited by the A 1 -selective receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine in a concentration-dependent manner (0.001-1.0 μmol/L). However, neither activation nor inhibition of A 1 AR altered basal or maximal (10 mU/mL) insulin-stimulated glucose transport. Our results suggest that adenosine contributes ~50% to insulin-stimulated muscle glucose transport by activating the A 1 AR. This effect is limited to increasing insulin sensitivity, but not to either basal or maximal insulin-stimulated glucose uptake in rat soleus muscle.