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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Microdialysis

glycerol

interstitial flow

phosphodiesterase inhibitors

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art (ämneskategori)

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