title: Characterization of adenosine-A1 receptor-mediated antilipolysis in rats by tissue microdialysis, 1H-spectroscopy, and glucose clamp studies.
abstract: 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.
authors.affiliation: Aventis Pharma Deutschland, Frankfurt/Main, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Schoelch
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuhlmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Gossel
authors.forename: Guenter
authors.initials: G
authors.lastname: Mueller
authors.forename: Claudia
authors.initials: C
authors.lastname: Neumann-Haefelin
authors.forename: Ulrich
authors.initials: U
authors.lastname: Belz
authors.forename: Juergen
authors.initials: J
authors.lastname: Kalisch
authors.forename: Gabriele
authors.initials: G
authors.lastname: Biemer-Daub
authors.forename: Werner
authors.initials: W
authors.lastname: Kramer
authors.forename: Hans-Paul
authors.initials: HP
authors.lastname: Juretschke
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Herling
mesh_terms: 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
chemical_list: D005230:Fatty Acids, Nonesterified; D043682:Receptor, Adenosine A1; D014280:Triglycerides; D017868:Cyclic AMP-Dependent Protein Kinases; D005990:Glycerol