title: Chronic effects of neuroendocrine regulatory peptide (NERP-1 and -2) on insulin secretion and gene expression in pancreatic β-cells.
abstract: Neuroendocrine regulatory peptides (NERP-1 and -2) are novel amidated peptides derived from VGF, a polypeptide secreted from neurons and endocrine cells through a regulated pathway. Dr. Nakazato Masamitsu reported that NERP-1 and -2 may have a local modulator function on the human endocrine system, and clearly showed expression of NERP-1 and -2 in human pancreas islets. Based on these data, we investigated the alteration of insulin secretion, insulin granule-related protein, and pancreas-specific transcription factors in response to NERPs expression. We confirmed the expression of NERP-1 and -2 in the pancreas of a human diabetes patient, in addition to diabetic animal models. When INS1 cells and primary rat islets were incubated with 10nM NERPs for 3 days, glucose-stimulated insulin secretion levels were blunted by NERP-1 and -2. The number of insulin granules released from the readily releasable pool, which is associated with the first phase of glucose-stimulated insulin release, was decreased by NERP-1 and -2. Insulin granule-related proteins and mRNAs were down-regulated by NERP-2 treatment. NERP-2 decreased the expression of BETA2/NeuroD and insulin and controlled the nucleo-cytoplasmic translocation of FOXO1 and Pdx-1. We observed that NERP-2 levels were dramatically increased in diabetic pancreas. In conclusion, NERP-2 may play an important role in insulin secretion through the regulation of insulin secretory granules and β-cell transcription factors. In addition, NERP-2 expression is increased in diabetic conditions. Therefore, we suggest that NERPs may be potent endogenous suppressors of glucose-dependent insulin secretion.
authors.affiliation: Department of Endocrinology and Metabolism, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea, Seoul 137-040, Republic of Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Endocrinology and Metabolism, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea, Seoul 137-040, Republic of Korea.
authors.forename: Marie
authors.initials: M
authors.lastname: Rhee
authors.affiliation: Department of Physiology, Keimyung University School of Medicine, Daegu 700-712, Republic of Korea.
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Neurology, Respirology, Endocrinology, and Metabolism, Div. of Internal Medicine, Faculty of Medicine, Univ. of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Pharmacology, National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Pharmacology, National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Minamino
authors.affiliation: Neurology, Respirology, Endocrinology, and Metabolism, Div. of Internal Medicine, Faculty of Medicine, Univ. of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
authors.affiliation: Department of Physiology, Keimyung University School of Medicine, Daegu 700-712, Republic of Korea.
authors.forename: Dae-Kyu
authors.initials: DK
authors.lastname: Song
authors.affiliation: Department of Endocrinology and Metabolism, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea, Seoul 137-040, Republic of Korea. Electronic address: yoonk@catholic.ac.kr.
authors.forename: Kun-Ho
authors.initials: KH
authors.lastname: Yoon
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D022142:Secretory Vesicles / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D007328:Insulin; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C523893:neuroendocrine regulatory peptide-1, human; C523895:neuroendocrine regulatory peptide-2, human
keywords: Glucose-stimulated insulin secretion (GSIS); Insulin secretory granules (ISG); Neuroendocrine regulatory peptides (NERPs); Pancreatic duodenal homeobox-1 (Pdx-1); Secretogranin (SCG); β-Cell E-box transcription factor (BETA2)