Various phosphodiesterase subtypes mediate the in vivo antilipolytic effect of insulin on adipose tissue and skeletal muscle in man.
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.
Enoksson
S
S
Department of Vascular Surgery, Huddinge University Hospital, Karolinska Institute, Sweden.
Degerman
E
E
Hagström-Toft
E
E
Large
V
V
Arner
P
P
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
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