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Research Article

Apelin Inhibits Insulin Secretion in Pancreatic β-Cells by Activation of PI3-Kinase-Phosphodiesterase 3B

Pages 142-154
Published online: 02 Nov 2009
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Aims. Apelin is secreted by adipocytes acting on APJ receptor and plays an important role in control of ing behavior, energy expenditure, and the regulation of body fluid homeostasis. The adipokine is regulated by insulin and tumor necrosis factor-α in adipose tissue, suggesting apelin is involved in the regulation of pancreatic function. In this study, we incubated rat insulinoma INS-1 cells producing insulin for 60 min and examined the effects of pyr1-apelin-13 on insulin secretion and the mechanism. Main Methods. INS-1 cells were incubated in the presence of various concentrations of glucose and/or apelin, glucagon-like peptide-1 (GLP-1), phosphoinositide 3-kinase (PI3-kinase) inhibitor, phosphodiesterase 3B (PDE3B) inhibitor, and cAMP analogues. We examined the effect of apelin on insulin secretion and the pathway of the action. Insulin concentrations were measured by radioimmunoassay. Key Findings. We found that apelin over the concentration range of 1–104 nmol/L inhibited the insulin response to glucose and GLP-1 and the concentration effect was biphasic. The effect of apelin was abolished when insulin secretion was induced with cAMP analogues that cannot be hydrolyzed by cyclic nucleotide PDE3B. Selective inhibitors of PDE3B and PI3-kinase completely prevent the apelin effect on insulin secretion and cAMP accumulation. Significance. These findings suggest that apelin exerts direct inhibitory actions on the pancreatic β-cells by activating PI3-kinase-dependent PDE3B and subsequently suppressing of cAMP levels.

Keywords: ApelinInsulinPDE3BcAMPPI3KGLP-1

Additional information


We thank LeiLei, Zhaohua Zhong, and Hong Ling for technical assistance.


The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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