Contribution of apelin to water balance, blood glucose control, and cardiovascular functions

The discovery of apelin, an endogenous ligand of the orphan APJ receptor, constitutes an important advance in both fundamental research and clinical medicine. Experimental data have shown that apelin has a diuretic effect via its central and renal actions: by inhibiting the phasic activity of vasopressinergic neurons and systemic secretion of vasopressin and its direct effect on the renal microcirculation and probably tubular function. Besides its diuretic action, when injected into the blood stream, apelin decreases blood pressure and increases the contractile force of the myocardium while decreasing pre- and post-load, actions opposing those of vasopressin and angiotensin II. Taken together, these data show that this new circulating vasoactive (neuro)peptide could play a crucial role in maintaining water and electrolyte balance and cardiovascular functions. Finally, a systemic injection of apelin in insulin-resistant mice decreases glycemia and enhances glucose uptake in skeletal muscle and adipose tissue, contributing to homeostatic control of blood glucose. Clinically, the development of non-peptide analogs of the apelin receptor could provide new therapeutic tools potentially useful for the treatment of heart failure, states of water and/or electrolyte retention, and type 2 diabetes mellitus. (C) 2010 Elsevier Masson SAS. All rights reserved.