The kallikrein-kinin system, angiotensin converting enzyme inhibitors and insulin sensitivity.
The therapeutic use of angiotensin converting enzyme (ACE) inhibitors, at a large scale, in arterial hypertension has showed that these molecules can exert beneficial effects on insulin sensitivity and may reduce the occurrence of type 2 diabetes mellitus. One hypothesis explaining these effects of ACE inhibitors may relate to their capacity to interfere with bradykinin (BK) metabolism and action. BK may participate in the regulation of substrate utilization by several tissues by improving blood flow and substrate delivery to the tissues and also by promoting translocation of glucose transporters. Moreover, BK has been shown to increase phosphorylation of insulin receptor and its cell substrates. BK also appears to improve the release of insulin. Furthermore, insulin may activate the kallikrein-kinin system, which consequently may increase its metabolic effects. However, in experimental diabetes mellitus, BK can participate to the inflammatory reaction leading to Langerhans islets destruction. In diabetes, whereas tissue kallikrein mRNA levels were reduced in several organs, an overexpression of kinin receptors, an increase in plasma levels of kininogens and kallikrein and an activation of the kinin system have all been reported. Lastly, kinins may be involved in the development of diabetic nephropathy. Reduction of kinin metabolism by ACE inhibitors might be involved in the beneficial effects exerted by these compounds in diabetic kidney functions.
Damas
J
J
Laboratoire de Physiologie humaine, Université de Liège, Avenue de l'hôpital 1 (Bât B23), Domaine du Sart-Tilman, Liège, Belgium.
Garbacki
N
N
Lefèbvre
P J
PJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001920:Bradykinin / Q000502:physiology; D003920:Diabetes Mellitus / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007328:Insulin / Q000378:metabolism / Q000502:physiology / Q000633:toxicity*; D000078790:Insulin Secretion; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007328:Insulin; D001920:Bradykinin