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Diabetes 53:1920-1926, 2004
© 2004 by the American Diabetes Association, Inc.

Characterization of Adenosine-A1 Receptor–Mediated Antilipolysis in Rats by Tissue Microdialysis, 1H-Spectroscopy, and Glucose Clamp Studies

Corinna Schoelch, Johanna Kuhlmann, Matthias Gossel, Guenter Mueller, Claudia Neumann-Haefelin, Ulrich Belz, Juergen Kalisch, Gabriele Biemer-Daub, Werner Kramer, Hans-Paul Juretschke, and Andreas W. Herling

From Aventis Pharma Deutschland, Frankfurt am Main, Germany

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 1H-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.


Address correspondence and reprint requests to Dr. Andreas W. Herling, Disease Group Metabolic Diseases, Pharmacology H 815/H 821, Aventis Pharma Deutschland, Industriepark Hoechst, 65926 Frankfurt/Main, Germany. E-mail: andreas.herling{at}aventis.com

Abbreviations: ARA, adenosine-A1 receptor agonist; FFA, free fatty acid; GIR, glucose infusion rate; gMT, gastrocnemius muscle tissue; HSL, hormone-sensitive lipase; IMTG, intramyocellular TG; mLPL, muscle lipoprotein lipase; MRS, magnetic resonance spectroscopy; PKA, protein kinase A; SAT, subcutaneous adipose tissue; SOL, m. soleus; TG, triglyceride; TIB, m. tibialis; VAT, visceral adipose tissue


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