Pancreatic islet APJ deletion reduces islet density and glucose tolerance in mice

Song Han, Ella W. Englander, Guillermo A. Gomez, Cristiana Rastellini, Thomas Quertermous, Ramendra K. Kundu, George H. Greeley

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Protection and replenishment of a functional pancreatic β-cell mass (BCM) are key goals of all diabetes therapies. Apelin, a small regulatory peptide, is the endogenous ligand for the apelin receptor (APJ) receptor. The apelin-APJ signaling system is expressed in rodent and human islet cells. Apelin exposure has been shown to inhibit and to stimulate insulin secretion. Our aim was to assess the influence of a selective APJ deletion in pancreatic islet cells on islet homeostasis and glucose tolerance in mice. Cre-LoxP strategy was utilized to mediate islet APJ deletion. APJ deletion in islet cells (APJΔislet) resulted in a significantly reduced islet size, density and BCM. An ip glucose tolerance test showed significantly impaired glucose clearance in APJΔislet mice. APJΔislet mice were not insulin resistant and in vivo glucose-stimulated insulin secretion was reduced modestly. In vitro glucose-stimulated insulin secretion showed a significantly reduced insulin secretion by islets from APJΔislet mice. Glucose clearance in response to ip glucose tolerance test in obese APJΔislet mice fed a chronic high-fat (HF) diet, but not pregnant APJΔislet mice, was impaired significantly. In addition, the obesity-induced adaptive elevations in mean islet size and fractional islet area were reduced significantly in obese APJΔislet mice when compared with wild-type mice. Together, these findings demonstrate a stimulatory role for the islet cell apelin-APJ signaling axis in regulation of pancreatic islet homeostasis and in metabolic induced β-cell hyperplasia. The results indicate the apelin-APJ system can be exploited for replenishment of BCM.

Original languageEnglish (US)
Pages (from-to)2451-2460
Number of pages10
JournalEndocrinology
Volume156
Issue number7
DOIs
StatePublished - Jul 1 2015

ASJC Scopus subject areas

  • Endocrinology

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    Han, S., Englander, E. W., Gomez, G. A., Rastellini, C., Quertermous, T., Kundu, R. K., & Greeley, G. H. (2015). Pancreatic islet APJ deletion reduces islet density and glucose tolerance in mice. Endocrinology, 156(7), 2451-2460. https://doi.org/10.1210/en.2014-1631