title: Angiopoietin-like peptide 4 regulates insulin secretion and islet morphology.
abstract: Insulin secretion from pancreatic islet β-cells is primarily regulated by the blood glucose level, and also modulated by a number of biological factors produced inside the islets or released from remote organs. Previous studies have shown that angiopoietin-like protein 4 (Angptl4) controls glucose and lipid metabolism through its actions in the liver, adipose tissue, and skeletal muscles. In this present study, we investigated the possible role of Angptl4 in the regulation of insulin secretion from pancreatic islets. Angptl4 was found to be highly expressed in the α-cells but not β-cells of rodent islets. Moreover, treatment of rodent islets with Angptl4 peptide potentiated glucose-stimulated insulin secretion through a protein kinase A-dependent mechanism. Consistently, Angptl4 knockout mice showed impaired glucose tolerance. In the cultured islets from Angptl4 knockout mice, glucose-stimulated insulin secretion was significantly lower than in islets from wild type mice. Angptl4 peptide replacement partially reversed this reduction. Moreover, Angptl4 knockout mice had dysmorphic islets with abnormally distributed α-cells. In contrast, the β-cell mass and distribution were not significantly altered in these knockout mice. Our current data collectively suggest that Angptl4 may play a critical role in the regulation of insulin secretion and islet morphogenesis.
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 05505, South Korea.
authors.forename: Hyun-Kyong
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 05505, South Korea; Division of Endocrinology and Metabolism, University of Ulsan College of Medicine, Seoul 05505, South Korea.
authors.forename: Obin
authors.initials: O
authors.lastname: Kwon
authors.affiliation: Department of Anatomy, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24341, South Korea.
authors.forename: Kyeong-Han
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Pharmacology, University of Ulsan College of Medicine, Seoul 05505, South Korea.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Osteoneurogen, Inc., Seoul 08501, South Korea.
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Youn
authors.affiliation: Department of Pharmacology, University of Ulsan College of Medicine, Seoul 05505, South Korea.
authors.forename: Seung-Whan
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 05505, South Korea; Division of Endocrinology and Metabolism, University of Ulsan College of Medicine, Seoul 05505, South Korea. Electronic address: mskim@amc.seoul.kr.
authors.forename: Min-Seon
authors.initials: MS
authors.lastname: Kim
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017207:Rats, Sprague-Dawley
chemical_list: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D007328:Insulin
keywords: Angiopoietin-like protein 4 (Angptl4); Insulin secretion; Pancreas; Protein kinase A