title: Various phosphodiesterase subtypes mediate the in vivo antilipolytic effect of insulin on adipose tissue and skeletal muscle in man.
abstract: The antilipolytic effect of insulin on human abdominal subcutaneous adipose tissue and skeletal muscle during local inhibition of cAMP-phosphodiesterases (PDEs) was investigated in vivo, by combining microdialysis with a euglycaemic, hyperinsulinaemic clamp. During hyperinsulinaemia, the glycerol concentration decreased by 40% in fat and by 33% in muscle. Addition of the selective PDE3-inhibitor amrinone abolished the insulin-induced decrease in adipose glycerol concentration, but did not influence the glycerol concentration in skeletal muscle. Nor did the PDE4-selective inhibitor rolipram or the PDE5-selective inhibitor dipyridamole influence the insulin-induced decrease in muscle tissue glycerol. However, the non-selective PDE-inhibitor theophylline counteracted the antilipolytic action of insulin at both sites. The specific activity of PDEs was also determined in both tissues. PDE3-activity was 36.8+/-6.4 pmol x min(-1) x mg(-1) in adipose tissue and 3.9+/-0.5 pmol x min(-1) x mg(-1) in muscle. PDE4-activity in skeletal muscle was high, i.e., 60.7+/-10.2 pmol x min(-1) x mg(-1) but 8.5 pmol x min(-1) x mg(-1) or less in adipose tissue. In conclusion, insulin inhibits lipolysis in adipose tissue and skeletal muscle by activation of different PDEs, suggesting a unique metabolic role of muscle lipolysis.
authors.affiliation: Department of Vascular Surgery, Huddinge University Hospital, Karolinska Institute, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Enoksson
authors.forename: E
authors.initials: E
authors.lastname: Degerman
authors.forename: E
authors.initials: E
authors.lastname: Hagström-Toft
authors.forename: V
authors.initials: V
authors.lastname: Large
authors.forename: P
authors.initials: P
authors.lastname: Arner
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000676:Amrinone / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015314:Dialysis Solutions / Q000737:chemistry / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism; D005260:Female; D005990:Glycerol / Q000032:analysis / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects* / Q000378:metabolism / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects* / Q000378:metabolism / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D020889:Rolipram; D002787:Sterol Esterase / Q000187:drug effects / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D015314:Dialysis Solutions; D007004:Hypoglycemic Agents; D007328:Insulin; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D014665:Vasodilator Agents; D000431:Ethanol; D004176:Dipyridamole; D013806:Theophylline; D002787:Sterol Esterase; D010727:Phosphoric Diester Hydrolases; D000676:Amrinone; D020889:Rolipram; D005990:Glycerol