Characterization of adenosine-A1 receptor-mediated antilipolysis in rats by tissue microdialysis, 1H-spectroscopy, and glucose clamp studies.
Increased supply of fatty acids to muscle and liver is causally involved in the insulin resistance syndrome. Using a tissue microdialysis technique in Wistar and Zucker fatty (ZF) rats, we determined tissue glycerol levels as a marker of lipolysis in gastrocnemius muscle (gMT), subcutaneous adipose (SAT), and visceral adipose tissue (VAT) as well as the reduction of plasma free fatty acids, glycerol, and triglycerides caused by the antilipolysis-specific adenosine-A1 receptor agonist (ARA). In Wistar and ZF rats, ARA significantly lowered dialysate glycerol levels in SAT, VAT, and gMT. Whereas in SAT and VAT the decrease in dialysate glycerol indicated adipocytic antilipolysis, this decrease in gMT was not caused by a direct effect of ARA on intramyocellular lipolysis, as demonstrated by the lack of inhibition of the protein kinase A activity ratio in gMT. In addition, no differences of the fed-starved-refed dynamics of intramyocellular triglyceride levels compared with untreated controls were measured by in vivo (1)H-spectroscopy, excluding any adenylate cyclase-independent antilipolysis in muscle. Treatment with ARA resulted in pronounced reductions of plasma free fatty acids, glycerol, and triglycerides. Furthermore, in ZF rats, ARA treatment caused an immediate improvement of peripheral insulin sensitivity measured by the euglycemic-hyperinsulinemic glucose clamp technique.
Schoelch
Corinna
C
Aventis Pharma Deutschland, Frankfurt/Main, Germany.
Kuhlmann
Johanna
J
Gossel
Matthias
M
Mueller
Guenter
G
Neumann-Haefelin
Claudia
C
Belz
Ulrich
U
Kalisch
Juergen
J
Biemer-Daub
Gabriele
G
Kramer
Werner
W
Juretschke
Hans-Paul
HP
Herling
Andreas W
AW
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood / Q000378:metabolism; D008066:Lipolysis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D040521:Subcutaneous Tissue / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014781:Viscera
D005230:Fatty Acids, Nonesterified; D043682:Receptor, Adenosine A1; D014280:Triglycerides; D017868:Cyclic AMP-Dependent Protein Kinases; D005990:Glycerol