1: Cell Metab. 2008 Nov;8(5):437-45. Apelin stimulates glucose utilization in normal and obese insulin-resistant mice. Dray C, Knauf C, Daviaud D, Waget A, Boucher J, Buléon M, Cani PD, Attané C, Guigné C, Carpéné C, Burcelin R, Castan-Laurell I, Valet P. Institut National de la Santé et de la Recherche Médicale, U858, Toulouse, France. Adipose tissue (AT) secretes several adipokines that influence insulin sensitivity and potentially link obesity to insulin resistance. Apelin, a peptide present in different tissues, is also secreted by adipocytes. Apelin is upregulated in obese and hyperinsulinemic humans and mice. Although a tight relation exists between the regulation of apelin and insulin, it remains largely unknown whether apelin affects whole-body glucose utilization. Herein, we show that in chow-fed mice, acute intravenous injection of apelin has a powerful glucose-lowering effect associated with enhanced glucose utilization in skeletal muscle and AT. Through in vivo and in vitro pharmacological and genetic approaches, we demonstrate the involvement of endothelial NO synthase, AMP-activated protein kinase, and Akt in apelin-stimulated glucose uptake in soleus muscle. Remarkably, in obese and insulin-resistant mice, apelin restored glucose tolerance and increased glucose utilization. Apelin could thus represent a promising target in the management of insulin resistance. PMID: 19046574 [PubMed - in process] Related Links Apelin, a newly identified adipokine up-regulated by insulin and obesity. [Endocrinology. 2005] PMID:15677759 The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice. [Regul Pept. 2005] PMID:15970338 Apelin and visfatin: unique "beneficial" adipokines upregulated in obesity? [Med Sci Monit. 2006] PMID:16733497 TNFalpha up-regulates apelin expression in human and mouse adipose tissue. [FASEB J. 2006] PMID:16723381 Insulin resistance associated to obesity: the link TNF-alpha. [Arch Physiol Biochem. 2008] PMID:18629684