Is captopril-induced improvement of insulin sensitivity mediated via endothelin?
Angiotensin-converting enzyme (ACE) inhibitors have been reported to improve insulin sensitivity during either short-term or long-term administration. Recent studies indicate that endothelin-1 (ET-1) has potent glycogenolytic effects in rat hepatocytes and may cause insulin resistance in rat adipocytes. In addition, ET may also have a role in stimulation of the hypothalamic-pituitary-adrenal axis. To test the hypothesis that part of the effect of captopril in enhancing insulin sensitivity may be mediated via ET and/or by glucocorticoids, we measured 24-h urinary excretion of ET and free cortisol before and after short-term treatment with captopril. The 24-h urinary immunoreactive endothelin (IR-ET) excretion decreased significantly (p < 0.05) from 65 +/- 4 ng at baseline to 42 +/- 3 ng after captopril treatment, whereas no significant change in the 24-h urinary free cortisol excretion was observed. Moreover, no significant change in the 24-h urinary IR-ET and free cortisol excretions was noted in the placebo-treated group. We speculate that ACE inhibitors may exert their effect on insulin sensitivity not only by blocking the renin-angiotensin and kinin systems but also by inhibiting production and/or release of ET.
Lam
H C
HC
Department of Medicine, Veterans General Hospital-Kaohsiung, Taiwan, Republic of China.
Lee
J K
JK
Chiang
H T
HT
Chuang
M J
MJ
Wang
M C
MC
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D016232:Endothelins / Q000502:physiology* / Q000652:urine; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D051381:Rats; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D016232:Endothelins; D002216:Captopril; D006854:Hydrocortisone