Voprosy meditsinskoi khimii (ISSN 0042-8809)

Possible participation of angiotensin-converting enzyme and of leukocyte elastase in pathogenesis of non-insulin dependentdiabetes mellitus

   
Dotsenko V.L., Demidova T.Yu., Neshkova E.A., Ametov A.S., Yarovaya G.A.
PubMed Id: 9634724
Year: 1998 vol: 44  issue:2  pages: 203-212
Abstract: It is commonly accepted that the tolerance to insulin and hyperglycemia of the patients with non-insulin dependent diabetes mellitus (NIDDM) is due to some defect of insulin receptors or disturbances in the signaling pathway of the cell. This disease is often accompanied by hypertension. In this paper the high activity of plasma kallikrein-kinin system (KKS) (kallikrein activity was 6-8 times higher than normal), of angiotensin-converting enzyme (ACE) (4 times greater than normal), and of leukocyte elastase (2.7 times higher than normal) were demonstrated in plasma of patients with NIDDM. Increasing of KKS activity was coincident with rising of ACE activity, which may be the cause of the fast bradykinin inactivation and arising of hypertension. The treatment with ACE inhibitor during 3 months (4 mg of Perindopril per day) decreased ACE activity in patients' plasma which was accompanied with decreasing of the arterial pressure and some restoration of the carbohydrate metabolism indicators. The hyperinsulinemic euglycaemic clamping of 7 patients with NIDDM and essential hypertension showed that ACE-inhibitor (Perindopril, 4 mg) prevented bradykinin from destruction and increased the glucose consumption by tissues. The high activity of polymorphonuclear leukocytes and secretion of the elastase in NIDDM patients' plasma and/or instability of plasmatic and granular membranes of leukocyte in conditions of hyperglycaemic plasma are probably the cause of endothelial irritation and high ACE secretion. Secondly, the leukocyte may be the cause of injuring and decreasing of susceptibility of the cell receptors for insulin and bradykinin.
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Reference: Dotsenko V.L., Demidova T.Yu., Neshkova E.A., Ametov A.S., Yarovaya G.A., Possible participation of angiotensin-converting enzyme and of leukocyte elastase in pathogenesis of non-insulin dependentdiabetes mellitus, Voprosy meditsinskoi khimii, 1998, vol: 44(2), 203-212.
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