Activation of alpha2-adrenergic receptors blunts epinephrine-induced lipolysis in subcutaneous adipose tissue during a hyperinsulinemic euglycemic clamp in men
Language English Country United States Media print
Document type Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't
PubMed
12900381
DOI
10.1152/ajpendo.00502.2002
PII: 285/3/E599
Knihovny.cz E-resources
- MeSH
- Epinephrine administration & dosage MeSH
- Adrenergic beta-Agonists administration & dosage MeSH
- Adrenergic alpha-Antagonists administration & dosage MeSH
- Receptors, Adrenergic, alpha-2 metabolism MeSH
- Adult MeSH
- Phentolamine administration & dosage MeSH
- Glycerol blood MeSH
- Glucose Clamp Technique MeSH
- Hyperinsulinism metabolism MeSH
- Insulin blood MeSH
- Isoproterenol administration & dosage MeSH
- Humans MeSH
- Lipolysis drug effects physiology MeSH
- Microdialysis MeSH
- Subcutaneous Tissue drug effects metabolism MeSH
- Sympathomimetics administration & dosage MeSH
- Adipose Tissue drug effects metabolism MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Controlled Clinical Trial MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Epinephrine MeSH
- Adrenergic beta-Agonists MeSH
- Adrenergic alpha-Antagonists MeSH
- Receptors, Adrenergic, alpha-2 MeSH
- Phentolamine MeSH
- Glycerol MeSH
- Insulin MeSH
- Isoproterenol MeSH
- Sympathomimetics MeSH
The aim of this study was to investigate whether hyperinsulinemia modifies adrenergic control of lipolysis, with particular attention paid to the involvement of antilipolytic alpha2-adrenergic receptors (AR). Eight healthy male subjects (age: 23.9 +/- 0.9 yr; body mass index: 23.8 +/- 1.9) were investigated during a 6-h euglycemichyperinsulinemic clamp and in control conditions. Before and during the clamp, the effect of graded perfusions of isoproterenol (0.1 and 1 microM) or epinephrine (1 and 10 microM) on the extracellular glycerol concentration in subcutaneous abdominal adipose tissue was evaluated by using the microdialysis method. Both isoproterenol and epinephrine induced a dose-dependent increase in extracellular glycerol concentration when infused for 60 min through the microdialysis probes before and during hours 3 and 6 of the clamp. The catecholamine-induced increase was significantly lower during the clamp than before it, with the inhibition being more pronounced in hour 6 of the clamp. Isoproterenol (1 microM)-induced lipolysis was reduced by 28 and 44% during hours 3 and 6 of the clamp, respectively, whereas the reduction of epinephrine (100 microM)-induced lipolysis was significantly greater (by 63 and 70%, P < 0.01 and P < 0.04, respectively) during the same time intervals. When epinephrine was infused in combination with 100 microM phentolamine (a nonselective alpha-AR antagonist), the inhibition of epinephrine (10 microM)-induced lipolysis was only of 19 and 40% during hours 3 and 6 of the clamp, respectively. The results demonstrate that, in situ, insulin counteracts the epinephrine-induced lipolysis in adipose tissue. The effect involves 1) reduction of lipolysis stimulation mediated by the beta-adrenergic pathway and 2) the antilipolytic component of epinephrine action mediated by alpha2-ARs.
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