Apelin stimulates glucose utilization in normal and obese insulin-resistant mice

Cell Metab. 2008 Nov;8(5):437-45. doi: 10.1016/j.cmet.2008.10.003.


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.

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Adipokines
  • Adipose Tissue / metabolism*
  • Animals
  • Apelin
  • Carrier Proteins / pharmacology
  • Carrier Proteins / physiology*
  • Glucose / metabolism*
  • Insulin Resistance / physiology*
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / metabolism
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • Obesity / metabolism*
  • Oncogene Protein v-akt / metabolism


  • Adipokines
  • Apelin
  • Apln protein, mouse
  • Carrier Proteins
  • Intercellular Signaling Peptides and Proteins
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Oncogene Protein v-akt
  • AMP-Activated Protein Kinases
  • Glucose