The present study was undertaken to investigate the effects of C-atrial natriuretic peptide (C-ANP(4-23)) in human adipose-derived stem cells differentiated into adipocytes over 10 days (1 mu M for 4 h). The intracellular cAMP, cGMP and protein kinase A levels were determined by ELISA and gene and protein expression were determined by qRT-PCR and Western blot, respectively, in the presence or absence of C-ANP(4-23). The levels of lipolysis and glucose uptake were also determined. C-ANP(4-23) treatment significantly increased the intracellular cAMP levels and the gene expression of glucose transporter type 4 (GLUT4) and protein kinase, AMP-activated, alpha 1 catalytic subunit (AMPK). Western blot showed a significant increase in GLUT4 and phosphor-AMPK alpha levels. Importantly, the adenylate cyclase inhibitor SQ22536 abolished these effects. Additionally, C-ANP(4-23) increased glucose uptake by 2-fold. Our results show that C-ANP(4-23) enhances glucose metabolism and might contribute to the development of new peptide-based therapies for metabolic diseases. (C) 2016 Elsevier Ireland Ltd. All rights reserved.