The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice.
Apelin is the endogenous ligand of the G-protein coupled apj receptor. Apelin is expressed in the brain, the hypothalamus and the stomach and was recently shown also to be an adipokine secreted from the adipocytes. Although apelin has been suggested to be involved in the regulation of food intake, it is not known whether the peptide affects islet function and glucose homeostasis. We show here that the apj receptor is expressed in pancreatic islets and that intravenous administration of full-length apelin-36 (2 nmol/kg) inhibits the rapid insulin response to intravenous glucose (1 g/kg) by 35% in C57BL/6J mice. Thus, the acute (1-5 min) insulin response to intravenous glucose was 682+/-23 pmol/l after glucose alone (n=17) and 445+/-58 pmol/l after glucose plus apelin-36 (n=18; P=0.017). This was associated with impaired glucose elimination (the 5-20 min glucose elimination was 2.9+/-0.1%/min after glucose alone versus 2.3+/-0.2%/min after glucose plus apelin-36, P=0.008). Apelin (2 nmol/kg) also inhibited the insulin response to intravenous glucose in obese insulin resistant high-fat fed C57BL/6J mice (P=0.041). After 60 min incubation of isolated islets from normal mice, insulin secretion in the presence of 16.7 mmol/l glucose was inhibited by apelin-36 at 1 mumol/l, whereas apelin-36 did not significantly affect insulin secretion at 2.8 or 8.3 mmol/l glucose or after stimulation of insulin secretion by KCl. Islet glucose oxidation at 16.7 mmol/l was not affected by apelin-36. We conclude that the apj receptor is expressed in pancreatic islets and that apelin-36 inhibits glucose-stimulated insulin secretion both in vivo and in vitro. This may suggest that the islet beta-cells are targets for apelin-36.
Sörhede Winzell
Maria
M
Department of Clinical Sciences, Division of Medicine, Lund University, B11 BMC, SE-221 84 Lund, Sweden.
Magnusson
Caroline
C
Ahrén
Bo
B
D054392:Adipokines; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse; D002352:Carrier Proteins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D005947:Glucose