RESP18, a homolog of the luminal domain IA-2, is found in dense core vesicles in pancreatic islet cells and is induced by high glucose

The regulated endocrine-specific protein, RESP18, first found in the rat pituitary, was thought to be regulated by dopaminergic drugs. Bioinformatics studies showed that RESP18 shares sequence homology with the luminal region of IA-2, a dense core vesicle (DCV) transmembrane protein involved in insu...

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Veröffentlicht in:Journal of endocrinology 2007-11, Vol.195 (2), p.313-321
Hauptverfasser: Zhang, Guofeng, Hirai, Hiroki, Cai, Tao, Miura, Junnosuke, Yu, Ping, Huang, Hanxia, Schiller, Martin R, Swaim, William D, Leapman, Richard D, Notkins, Abner L
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container_issue 2
container_start_page 313
container_title Journal of endocrinology
container_volume 195
creator Zhang, Guofeng
Hirai, Hiroki
Cai, Tao
Miura, Junnosuke
Yu, Ping
Huang, Hanxia
Schiller, Martin R
Swaim, William D
Leapman, Richard D
Notkins, Abner L
description The regulated endocrine-specific protein, RESP18, first found in the rat pituitary, was thought to be regulated by dopaminergic drugs. Bioinformatics studies showed that RESP18 shares sequence homology with the luminal region of IA-2, a dense core vesicle (DCV) transmembrane protein involved in insulin secretion. The present study was initiated to examine the genomic structure and subcellular localization of RESP18 and the effect of glucose on its expression. Human RESP18 was isolated from a pancreas cDNA library and its subcellular localization was determined by immunoelectron microscopy. MIN6 cells and mouse islets were used to study the effect of glucose on RESP18 expression. Bioinformatics analysis revealed that RESP18 and IA-2 are tandemly arranged within a 45 kb region on human chromosome 2 and share common intron–exon boundaries. By confocal microscopy, RESP18 was found in α, β and δ cells in the pancreatic islets. Electron microscopy revealed that RESP18 is present in the lumen of DCVs. The expression of RESP18 in β cells is markedly increased following exposure to high glucose and also elevated in the islets of diabetic, but not non-diabetic, NOD mice. We conclude that RESP18 is a luminal protein of DCVs and its expression is regulated by exposure to glucose.
doi_str_mv 10.1677/JOE-07-0252
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Bioinformatics studies showed that RESP18 shares sequence homology with the luminal region of IA-2, a dense core vesicle (DCV) transmembrane protein involved in insulin secretion. The present study was initiated to examine the genomic structure and subcellular localization of RESP18 and the effect of glucose on its expression. Human RESP18 was isolated from a pancreas cDNA library and its subcellular localization was determined by immunoelectron microscopy. MIN6 cells and mouse islets were used to study the effect of glucose on RESP18 expression. Bioinformatics analysis revealed that RESP18 and IA-2 are tandemly arranged within a 45 kb region on human chromosome 2 and share common intron–exon boundaries. By confocal microscopy, RESP18 was found in α, β and δ cells in the pancreatic islets. Electron microscopy revealed that RESP18 is present in the lumen of DCVs. The expression of RESP18 in β cells is markedly increased following exposure to high glucose and also elevated in the islets of diabetic, but not non-diabetic, NOD mice. We conclude that RESP18 is a luminal protein of DCVs and its expression is regulated by exposure to glucose.</description><identifier>ISSN: 0022-0795</identifier><identifier>EISSN: 1479-6805</identifier><identifier>DOI: 10.1677/JOE-07-0252</identifier><identifier>PMID: 17951542</identifier><identifier>CODEN: JOENAK</identifier><language>eng</language><publisher>Colchester: BioScientifica</publisher><subject>Animals ; Biological and medical sciences ; Cell Line, Tumor ; Chromosome Mapping ; Chromosomes, Human, Pair 2 ; Computational Biology ; Diabetes Mellitus, Type 1 - metabolism ; Dose-Response Relationship, Drug ; Endocrine pancreas ; Evolution, Molecular ; Fundamental and applied biological sciences. Psychology ; Genome, Human ; Glucose - administration &amp; dosage ; Glucose - pharmacology ; Hormones. 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Bioinformatics studies showed that RESP18 shares sequence homology with the luminal region of IA-2, a dense core vesicle (DCV) transmembrane protein involved in insulin secretion. The present study was initiated to examine the genomic structure and subcellular localization of RESP18 and the effect of glucose on its expression. Human RESP18 was isolated from a pancreas cDNA library and its subcellular localization was determined by immunoelectron microscopy. MIN6 cells and mouse islets were used to study the effect of glucose on RESP18 expression. Bioinformatics analysis revealed that RESP18 and IA-2 are tandemly arranged within a 45 kb region on human chromosome 2 and share common intron–exon boundaries. By confocal microscopy, RESP18 was found in α, β and δ cells in the pancreatic islets. Electron microscopy revealed that RESP18 is present in the lumen of DCVs. 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Bioinformatics studies showed that RESP18 shares sequence homology with the luminal region of IA-2, a dense core vesicle (DCV) transmembrane protein involved in insulin secretion. The present study was initiated to examine the genomic structure and subcellular localization of RESP18 and the effect of glucose on its expression. Human RESP18 was isolated from a pancreas cDNA library and its subcellular localization was determined by immunoelectron microscopy. MIN6 cells and mouse islets were used to study the effect of glucose on RESP18 expression. Bioinformatics analysis revealed that RESP18 and IA-2 are tandemly arranged within a 45 kb region on human chromosome 2 and share common intron–exon boundaries. By confocal microscopy, RESP18 was found in α, β and δ cells in the pancreatic islets. Electron microscopy revealed that RESP18 is present in the lumen of DCVs. The expression of RESP18 in β cells is markedly increased following exposure to high glucose and also elevated in the islets of diabetic, but not non-diabetic, NOD mice. We conclude that RESP18 is a luminal protein of DCVs and its expression is regulated by exposure to glucose.</abstract><cop>Colchester</cop><pub>BioScientifica</pub><pmid>17951542</pmid><doi>10.1677/JOE-07-0252</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; EZB-FREE-00999 freely available EZB journals
subjects Animals
Biological and medical sciences
Cell Line, Tumor
Chromosome Mapping
Chromosomes, Human, Pair 2
Computational Biology
Diabetes Mellitus, Type 1 - metabolism
Dose-Response Relationship, Drug
Endocrine pancreas
Evolution, Molecular
Fundamental and applied biological sciences. Psychology
Genome, Human
Glucose - administration & dosage
Glucose - pharmacology
Hormones. Régulation
Humans
Insulinoma - metabolism
Insulinoma - pathology
Islets of Langerhans - cytology
Islets of Langerhans - metabolism
Mice
Mice, Inbred NOD
Microscopy, Confocal
Microscopy, Electron
Microscopy, Immunoelectron
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Receptor-Like Protein Tyrosine Phosphatases, Class 8 - genetics
Receptor-Like Protein Tyrosine Phosphatases, Class 8 - metabolism
Regular papers
Secretory Vesicles - metabolism
Subcellular Fractions - metabolism
Tissue Distribution
Up-Regulation
Vertebrates: endocrinology
title RESP18, a homolog of the luminal domain IA-2, is found in dense core vesicles in pancreatic islet cells and is induced by high glucose
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