Regenerating 1 and 3b Gene Expression in the Pancreas of Type 2 Diabetic Goto-Kakizaki (GK) Rats
Publication Date
February 26, 2014
Journal
PLOS ONE
Authors
Sophie Calderari, Jean Claude Irminger, Marie Hélène Giroix, Jan A. Ehses, et al
Volume
9
Issue
2
Pages
e90045
DOI
https://dx.plos.org/10.1371/journal.pone.0090045
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0090045
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/24587207
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3936001
Europe PMC
http://europepmc.org/abstract/MED/24587207
Web of Science
000332389000131
Scopus
84896384374
Mendeley
http://www.mendeley.com/research/regenerating-1-3b-gene-expression-pancreas-type-2-diabetic-gotokakizaki-gk-rats
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Mendeley | Further Information

{"title"=>"Regenerating 1 and 3b gene expression in the pancreas of type 2 diabetic Goto-Kakizaki (GK) rats", "type"=>"journal", "authors"=>[{"first_name"=>"Sophie", "last_name"=>"Calderari", "scopus_author_id"=>"12765618600"}, {"first_name"=>"Jean Claude", "last_name"=>"Irminger", "scopus_author_id"=>"6603785209"}, {"first_name"=>"Marie Hélène", "last_name"=>"Giroix", "scopus_author_id"=>"7005558567"}, {"first_name"=>"Jan A.", "last_name"=>"Ehses", "scopus_author_id"=>"6602491913"}, {"first_name"=>"Marie Noëlle", "last_name"=>"Gangnerau", "scopus_author_id"=>"6701913178"}, {"first_name"=>"Josiane", "last_name"=>"Coulaud", "scopus_author_id"=>"7101649282"}, {"first_name"=>"Katharina", "last_name"=>"Rickenbach", "scopus_author_id"=>"8839459500"}, {"first_name"=>"Dominique", "last_name"=>"Gauguier", "scopus_author_id"=>"7004461140"}, {"first_name"=>"Philippe", "last_name"=>"Halban", "scopus_author_id"=>"7005900341"}, {"first_name"=>"Patricia", "last_name"=>"Serradas", "scopus_author_id"=>"6701653317"}, {"first_name"=>"Françoise", "last_name"=>"Homo-Delarche", "scopus_author_id"=>"7005407545"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"372630169", "sgr"=>"84896384374", "pmid"=>"24587207", "scopus"=>"2-s2.0-84896384374", "isbn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0090045", "issn"=>"19326203"}, "id"=>"232e1a37-e421-3ef2-a15e-02a27679d595", "abstract"=>"Regenerating (REG) proteins are associated with islet development, β-cell damage, diabetes and pancreatitis. Particularly, REG-1 and REG-3-beta are involved in cell growth/survival and/or inflammation and the Reg1 promoter contains interleukin-6 (IL-6)-responsive elements. We showed by transcriptome analysis that islets of Goto-Kakizaki (GK) rats, a model of spontaneous type 2 diabetes, overexpress Reg1, 3α, 3β and 3γ, vs Wistar islets. Goto-Kakizaki rat islets also exhibit increased cytokine/chemokine expression/release, particularly IL-6. Here we analyzed Reg1 and Reg3β expression and REG-1 immuno-localization in the GK rat pancreas in relationship with inflammation. Isolated pancreatic islets and acinar tissue from male adult Wistar and diabetic GK rats were used for quantitative RT-PCR analysis. REG-1 immunohistochemistry was performed on paraffin sections with a monoclonal anti-rat REG-1 antibody. Islet cytokine/chemokine release was measured after 48 h-culture. Islet macrophage-positive area was quantified on cryostat sections using anti-CD68 and major histocompatibility complex (MHC) class II antibodies. Pancreatic exocrine-to-endocrine Reg1 and Reg3β mRNA ratios were markedly increased in Wistar vs GK rats. Conversely, both genes were upregulated in isolated GK rat islets. These findings were unexpected, because Reg genes are expressed in the pancreatic acinar tissue. However, we observed REG-1 protein labeling in acinar peri-ductal tissue close to islets and around large, often disorganized, GK rat islets, which may retain acinar cells due to their irregular shape. These large islets also showed peri-islet macrophage infiltration and increased release of various cytokines/chemokines, particularly IL-6. Thus, IL-6 might potentially trigger acinar REG-1 expression and secretion in the vicinity of large diabetic GK rat islets. This increased acinar REG-1 expression might reflect an adaptive though unsuccessful response to deleterious microenvironment.", "link"=>"http://www.mendeley.com/research/regenerating-1-3b-gene-expression-pancreas-type-2-diabetic-gotokakizaki-gk-rats", "reader_count"=>14, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1398675"], "description"=>"<p>The islets were selected as a function of their size by handpicking under a stereomicroscope. (A) Representative photomicrographs of islets cultured on ECM matrix in the presence of 11 mM glucose. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090045#pone.0090045.s006\" target=\"_blank\">Figure S6</a> is indicative of the groups of small and large islets which were compared between Wistar and GK rats. Note the disturbed shape and/or the ring of small cells (possibly, acinar and/or myeloid) around both types of isolated GK islets. (B, C, D, E): IL-6, CCL2, CCL3 and CXCL1 islet release, respectively. Wistar and GK islets were pooled separately and plated in triplicate. In a given experiment, cytokine/chemokine levels were normalized to total islet protein content after 48 h culture; in (B–E), data are presented as mean values ± SEM, n = 3 different islet isolations for each group of rats; in (F) data are presented for large islets, as mean values ± SEM (n = 3) of the ratio of GK <i>versus</i> control Wistar values in each experiment. *p<0.05 and **p<0.01 <i>vs</i> corresponding Wistar islets, as analyzed by Student’s <i>t</i> test for unpaired data. CCL2, CC-chemokine ligand-2 or monocyte chemoattractant protein-1 (MCP-1); CCL3, CC-chemokine ligand-3 or macrophage inflammatory protein-1α (MIP-1α); CXCL1, CXC-chemokine ligand-1 or chemokine GRO1/KC (murine IL-8 equivalent); IL-6, interleukin-6.</p>", "links"=>[], "tags"=>["genetics", "histology", "immunology", "Immune system", "cytokines", "Model organisms", "Animal models", "rat", "Molecular cell biology", "Anatomy and physiology", "Endocrinology", "Diabetic endocrinology", "Diabetes mellitus type 2", "Metabolic disorders", "islets", "3-month-old", "wistar", "gk"], "article_id"=>944717, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sophie Calderari", "Jean-Claude Irminger", "Marie-Hélène Giroix", "Jan A. Ehses", "Marie-Noëlle Gangnerau", "Josiane Coulaud", "Katharina Rickenbach", "Dominique Gauguier", "Philippe Halban", "Patricia Serradas", "Françoise Homo-Delarche"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090045.g003", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vitro_cytokine_chemokine_release_by_small_and_large_islets_from_3_month_old_Wistar_and_GK_rats_/944717", "title"=>"<i>In vitro</i> cytokine/chemokine release by small and large islets from 3-month-old Wistar (□) and GK (▪) rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-26 02:50:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398674"], "description"=>"<p>Serial staining (brown) for: (A, H) insulin (β-cell marker), (B, I) glucagon+somatostatin+pancreatic polypeptide cocktail (non-β cell marker), (C, J) α-amylase (acinar cell marker), and (D, K, and F–G, M–N) REG-1. For REG-1 labeling, we used the monoclonal anti-rat REG-1 antibody from Hiroshi Okamoto (Japan). REG-1 negative controls are shown in (E, L). In (F–G) and (M–N), the border of islets is defined by the red dashed line. In Fig. 2N, “d” means “duct”.</p>", "links"=>[], "tags"=>["genetics", "histology", "immunology", "Immune system", "cytokines", "Model organisms", "Animal models", "rat", "Molecular cell biology", "Anatomy and physiology", "Endocrinology", "Diabetic endocrinology", "Diabetes mellitus type 2", "Metabolic disorders", "pancreas", "immunochemistry", "4-month-old", "wistar", "gk"], "article_id"=>944716, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sophie Calderari", "Jean-Claude Irminger", "Marie-Hélène Giroix", "Jan A. Ehses", "Marie-Noëlle Gangnerau", "Josiane Coulaud", "Katharina Rickenbach", "Dominique Gauguier", "Philippe Halban", "Patricia Serradas", "Françoise Homo-Delarche"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090045.g002", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_pancreas_immunochemistry_in_4_month_old_male_Wistar_A_8211_G_and_GK_H_8211_N_rats_/944716", "title"=>"Representative pancreas immunochemistry in 4-month-old male Wistar (A–G) and GK (H–N) rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-26 02:50:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398671"], "description"=>"<p>Values are means ± SEM of three distinct experiments measured by quantitative RT-PCR for: A) islet-depleted exocrine-to-endocrine (isolated islets) tissue ratio; B) isolated islets: mRNA levels were expressed as the fold change in GK <i>vs</i> corresponding Wistar group. Glyceraldehyde-3-phosphate dehydrogenase was used as housekeeping gene. Three different islet isolations for each group of rats, * <i>p</i><0.05 and ** <i>p</i><0.01 <i>vs</i> Wistar rats, as analyzed by Student’s <i>t</i> test for unpaired data.</p>", "links"=>[], "tags"=>["genetics", "histology", "immunology", "Immune system", "cytokines", "Model organisms", "Animal models", "rat", "Molecular cell biology", "Anatomy and physiology", "Endocrinology", "Diabetic endocrinology", "Diabetes mellitus type 2", "Metabolic disorders", "pancreas", "4-month-old", "wistar", "gk"], "article_id"=>944713, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sophie Calderari", "Jean-Claude Irminger", "Marie-Hélène Giroix", "Jan A. Ehses", "Marie-Noëlle Gangnerau", "Josiane Coulaud", "Katharina Rickenbach", "Dominique Gauguier", "Philippe Halban", "Patricia Serradas", "Françoise Homo-Delarche"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090045.g001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regenerating_gene_1_Reg1_and_Reg3_946_gene_expression_in_the_pancreas_of_4_month_old_Wistar_and_GK_rats_/944713", "title"=>"Regenerating gene-1(<i>Reg1</i>) and <i>Reg3β</i> gene expression in the pancreas of 4-month-old Wistar (□) and GK (▪) rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-26 02:50:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398679"], "description"=>"<p>All data were determined under fed conditions. Values (pg/ml) are mean ± SEM for the number (<i>n</i>) of animals. Statistical analysis used the Student <i>t</i>-test for unpaired data. No significant difference in circulating cytokine levels was observed between 3- and 4-month-old Wistar and GK rats. CCL2, CC-chemokine ligand-2 or monocyte chemoattractant protein-1 (MCP-1); CCL3, CC-chemokine ligand-3 or macrophage inflammatory protein-1α (MIP-1α); CXCL1, CXC-chemokine ligand-1 or chemokine GRO1/KC (murine IL-8 equivalent); IL-6, Interleukin-6.</p>", "links"=>[], "tags"=>["genetics", "histology", "immunology", "Immune system", "cytokines", "Model organisms", "Animal models", "rat", "Molecular cell biology", "Anatomy and physiology", "Endocrinology", "Diabetic endocrinology", "Diabetes mellitus type 2", "Metabolic disorders", "wistar", "gk", "rats"], "article_id"=>944721, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sophie Calderari", "Jean-Claude Irminger", "Marie-Hélène Giroix", "Jan A. Ehses", "Marie-Noëlle Gangnerau", "Josiane Coulaud", "Katharina Rickenbach", "Dominique Gauguier", "Philippe Halban", "Patricia Serradas", "Françoise Homo-Delarche"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090045.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Circulating_cytokines_chemokines_in_Wistar_and_GK_rats_as_a_function_of_age_/944721", "title"=>"Circulating cytokines/chemokines in Wistar and GK rats as a function of age.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-26 02:50:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398678"], "description"=>"<p>Analysis of serial pancreas sections for 3 GK rats. Correlation coefficient (r = 0.573, <i>p</i><0.025) between CD68<sup>+</sup> area and total islet area (C). Correlation coefficient (r = 0.950, <i>p</i> = 0.003) between MHC class II<sup>+</sup> area and total islet area (D). Correlations were assessed with non-parametric Spearman’s rank correlation test. MHC, major histocompatibity complex.</p>", "links"=>[], "tags"=>["genetics", "histology", "immunology", "Immune system", "cytokines", "Model organisms", "Animal models", "rat", "Molecular cell biology", "Anatomy and physiology", "Endocrinology", "Diabetic endocrinology", "Diabetes mellitus type 2", "Metabolic disorders", "cd68", "mhc", "ii", "2-month-old", "gk", "pancreas"], "article_id"=>944720, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sophie Calderari", "Jean-Claude Irminger", "Marie-Hélène Giroix", "Jan A. Ehses", "Marie-Noëlle Gangnerau", "Josiane Coulaud", "Katharina Rickenbach", "Dominique Gauguier", "Philippe Halban", "Patricia Serradas", "Françoise Homo-Delarche"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090045.g004", "stats"=>{"downloads"=>1, "page_views"=>52, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunohistochemistry_for_CD68_A_and_MHC_class_II_B_in_2_month_old_GK_rat_pancreas_sections_/944720", "title"=>"Immunohistochemistry for CD68 (A) and MHC class II (B) in 2-month-old GK rat pancreas sections.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-26 02:50:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398692", "https://ndownloader.figshare.com/files/1398693", "https://ndownloader.figshare.com/files/1398694", "https://ndownloader.figshare.com/files/1398695", "https://ndownloader.figshare.com/files/1398696", "https://ndownloader.figshare.com/files/1398697"], "description"=>"<div><p>Regenerating (REG) proteins are associated with islet development, β-cell damage, diabetes and pancreatitis. Particularly, REG-1 and REG-3-beta are involved in cell growth/survival and/or inflammation and the <i>Reg1</i> promoter contains interleukin-6 (IL-6)-responsive elements. We showed by transcriptome analysis that islets of Goto-Kakizaki (GK) rats, a model of spontaneous type 2 diabetes, overexpress <i>Reg1</i>, <i>3α</i>, <i>3β</i> and <i>3γ</i>, <i>vs</i> Wistar islets. Goto-Kakizaki rat islets also exhibit increased cytokine/chemokine expression/release, particularly IL-6. Here we analyzed <i>Reg1</i> and <i>Reg3β</i> expression and REG-1 immuno-localization in the GK rat pancreas in relationship with inflammation. Isolated pancreatic islets and acinar tissue from male adult Wistar and diabetic GK rats were used for quantitative RT-PCR analysis. REG-1 immunohistochemistry was performed on paraffin sections with a monoclonal anti-rat REG-1 antibody. Islet cytokine/chemokine release was measured after 48 h-culture. Islet macrophage-positive area was quantified on cryostat sections using anti-CD68 and major histocompatibility complex (MHC) class II antibodies. Pancreatic exocrine-to-endocrine <i>Reg1</i> and <i>Reg3β</i> mRNA ratios were markedly increased in Wistar <i>vs</i> GK rats. Conversely, both genes were upregulated in isolated GK rat islets. These findings were unexpected, because <i>Reg</i> genes are expressed in the pancreatic acinar tissue. However, we observed REG-1 protein labeling in acinar peri-ductal tissue close to islets and around large, often disorganized, GK rat islets, which may retain acinar cells due to their irregular shape. These large islets also showed peri-islet macrophage infiltration and increased release of various cytokines/chemokines, particularly IL-6. Thus, IL-6 might potentially trigger acinar REG-1 expression and secretion in the vicinity of large diabetic GK rat islets. This increased acinar REG-1 expression might reflect an adaptive though unsuccessful response to deleterious microenvironment.</p></div>", "links"=>[], "tags"=>["genetics", "histology", "immunology", "Immune system", "cytokines", "Model organisms", "Animal models", "rat", "Molecular cell biology", "Anatomy and physiology", "Endocrinology", "Diabetic endocrinology", "Diabetes mellitus type 2", "Metabolic disorders", "pancreas", "diabetic", "goto-kakizaki", "rats"], "article_id"=>944726, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sophie Calderari", "Jean-Claude Irminger", "Marie-Hélène Giroix", "Jan A. Ehses", "Marie-Noëlle Gangnerau", "Josiane Coulaud", "Katharina Rickenbach", "Dominique Gauguier", "Philippe Halban", "Patricia Serradas", "Françoise Homo-Delarche"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0090045.s001", "https://dx.doi.org/10.1371/journal.pone.0090045.s002", "https://dx.doi.org/10.1371/journal.pone.0090045.s003", "https://dx.doi.org/10.1371/journal.pone.0090045.s004", "https://dx.doi.org/10.1371/journal.pone.0090045.s005", "https://dx.doi.org/10.1371/journal.pone.0090045.s006"], "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regenerating_1_and_3b_Gene_Expression_in_the_Pancreas_of_Type_2_Diabetic_Goto_Kakizaki_GK_Rats/944726", "title"=>"<i>Regenerating 1</i> and <i>3b</i> Gene Expression in the Pancreas of Type 2 Diabetic Goto-Kakizaki (GK) Rats", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-26 02:50:11"}

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