Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice

1 Fraser Laboratories, Department of Medicine, and 3 Department of Surgery, McGill University, Montreal, Quebec H3A 1A1, Canada; and 2 Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopapthic Medicine, Ohio University, Athens, Ohio 45701 Submitted 22 September 20...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:American journal of physiology: endocrinology and metabolism 2004-09, Vol.287 (3), p.E405-E413
Hauptverfasser: Liu, Jun-Li, Coschigano, Karen T, Robertson, Katie, Lipsett, Mark, Guo, Yubin, Kopchick, John J, Kumar, Ujendra, Liu, Ye Lauren
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page E413
container_issue 3
container_start_page E405
container_title American journal of physiology: endocrinology and metabolism
container_volume 287
creator Liu, Jun-Li
Coschigano, Karen T
Robertson, Katie
Lipsett, Mark
Guo, Yubin
Kopchick, John J
Kumar, Ujendra
Liu, Ye Lauren
description 1 Fraser Laboratories, Department of Medicine, and 3 Department of Surgery, McGill University, Montreal, Quebec H3A 1A1, Canada; and 2 Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopapthic Medicine, Ohio University, Athens, Ohio 45701 Submitted 22 September 2003 ; accepted in final form 5 May 2004 Growth hormone, acting through its receptor (GHR), plays an important role in carbohydrate metabolism and in promoting postnatal growth. GHR gene-deficient (GHR –/– ) mice exhibit severe growth retardation and proportionate dwarfism. To assess the physiological relevance of growth hormone actions, GHR –/– mice were used to investigate their phenotype in glucose metabolism and pancreatic islet function. Adult GHR –/– mice exhibited significant reductions in the levels of blood glucose and insulin, as well as insulin mRNA accumulation. Immunohistochemical analysis of pancreatic sections revealed normal distribution of the islets despite a significantly smaller size. The average size of the islets found in GHR –/– mice was only one-third of that in wild-type littermates. Total -cell mass was reduced 4.5-fold in GHR –/– mice, significantly more than their body size reduction. This reduction in pancreatic islet mass appears to be related to decreases in proliferation and cell growth. GHR –/– mice were different from the human Laron syndrome in serum insulin level, insulin responsiveness, and obesity. We conclude that growth hormone signaling is essential for maintaining pancreatic islet size, stimulating islet hormone production, and maintaining normal insulin sensitivity and glucose homeostasis. glucose homeostasis; immunohistochemistry; Laron syndrome; insulin tolerance test Address for reprint requests and other correspondence: J.-L. Liu, Fraser Laboratories, M3–15, Royal Victoria Hospital, 687 Pine Ave. West, Montreal, QC H3A 1A1, Canada (E-mail: jun-li.liu{at}mcgill.ca ).
doi_str_mv 10.1152/ajpendo.00423.2003
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_15138153</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>66782120</sourcerecordid><originalsourceid>FETCH-LOGICAL-c484t-4d5b698a2486e1776c2f1b555001fe80cae91ee8003ca77bde6638b04c5ccc93</originalsourceid><addsrcrecordid>eNqFkU9v1DAQxS0EokvhC3BAPnHL4j9x4hxRaQGpEpe9W44z2UyVxMF2KFvx4fF2t-oJcfLY83tPnnmEvOdsy7kSn-zdAnPnt4yVQm4FY_IF2eSGKLhS6iXZMN7IguuyuSBvYrxjjNWqFK_JBVdcaq7khvz5gjGsS0I_U9_TffD3aaCDD5OfgQZwsCQf6B7yzdk1QqQdTjhjHKCji51dAJvQUYwjJBrxAaidO4qPjQjHKq4jzjTCHDHhL0yH_EYndPCWvOrtGOHd-bwku5vr3dW34vbH1-9Xn28LV-oyFWWn2qrRVpS6Al7XlRM9b_OIjPEeNHMWGg65YNLZum47qCqpW1Y65Zxr5CX5eLJdgv-5QkxmwuhgHO0Mfo2mqmotuGD_BQXPC5VMZlCcQBd8jAF6swScbDgYzswxG3POxjxmY47ZZNGHs_vaTtA9S85hZKA5AQPuh3sMYJbhENGPfn8wN-s47uB3enIWujbSXJdMmaXrs7b4t_bpM88a-Rc_tLQH</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>21193303</pqid></control><display><type>article</type><title>Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice</title><source>MEDLINE</source><source>American Physiological Society</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Liu, Jun-Li ; Coschigano, Karen T ; Robertson, Katie ; Lipsett, Mark ; Guo, Yubin ; Kopchick, John J ; Kumar, Ujendra ; Liu, Ye Lauren</creator><creatorcontrib>Liu, Jun-Li ; Coschigano, Karen T ; Robertson, Katie ; Lipsett, Mark ; Guo, Yubin ; Kopchick, John J ; Kumar, Ujendra ; Liu, Ye Lauren</creatorcontrib><description>1 Fraser Laboratories, Department of Medicine, and 3 Department of Surgery, McGill University, Montreal, Quebec H3A 1A1, Canada; and 2 Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopapthic Medicine, Ohio University, Athens, Ohio 45701 Submitted 22 September 2003 ; accepted in final form 5 May 2004 Growth hormone, acting through its receptor (GHR), plays an important role in carbohydrate metabolism and in promoting postnatal growth. GHR gene-deficient (GHR –/– ) mice exhibit severe growth retardation and proportionate dwarfism. To assess the physiological relevance of growth hormone actions, GHR –/– mice were used to investigate their phenotype in glucose metabolism and pancreatic islet function. Adult GHR –/– mice exhibited significant reductions in the levels of blood glucose and insulin, as well as insulin mRNA accumulation. Immunohistochemical analysis of pancreatic sections revealed normal distribution of the islets despite a significantly smaller size. The average size of the islets found in GHR –/– mice was only one-third of that in wild-type littermates. Total -cell mass was reduced 4.5-fold in GHR –/– mice, significantly more than their body size reduction. This reduction in pancreatic islet mass appears to be related to decreases in proliferation and cell growth. GHR –/– mice were different from the human Laron syndrome in serum insulin level, insulin responsiveness, and obesity. We conclude that growth hormone signaling is essential for maintaining pancreatic islet size, stimulating islet hormone production, and maintaining normal insulin sensitivity and glucose homeostasis. glucose homeostasis; immunohistochemistry; Laron syndrome; insulin tolerance test Address for reprint requests and other correspondence: J.-L. Liu, Fraser Laboratories, M3–15, Royal Victoria Hospital, 687 Pine Ave. West, Montreal, QC H3A 1A1, Canada (E-mail: jun-li.liu{at}mcgill.ca ).</description><identifier>ISSN: 0193-1849</identifier><identifier>EISSN: 1522-1555</identifier><identifier>DOI: 10.1152/ajpendo.00423.2003</identifier><identifier>PMID: 15138153</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Blood Glucose - metabolism ; Cell Division ; Glucagon - blood ; Glucose - metabolism ; Growth Hormone - physiology ; Homeostasis ; Insulin - blood ; Insulin - physiology ; Islets of Langerhans - anatomy &amp; histology ; Islets of Langerhans - growth &amp; development ; Mice ; Mice, Knockout - genetics ; Obesity - genetics ; Receptors, Somatotropin - genetics ; Receptors, Somatotropin - physiology</subject><ispartof>American journal of physiology: endocrinology and metabolism, 2004-09, Vol.287 (3), p.E405-E413</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-4d5b698a2486e1776c2f1b555001fe80cae91ee8003ca77bde6638b04c5ccc93</citedby><cites>FETCH-LOGICAL-c484t-4d5b698a2486e1776c2f1b555001fe80cae91ee8003ca77bde6638b04c5ccc93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3025,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15138153$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Jun-Li</creatorcontrib><creatorcontrib>Coschigano, Karen T</creatorcontrib><creatorcontrib>Robertson, Katie</creatorcontrib><creatorcontrib>Lipsett, Mark</creatorcontrib><creatorcontrib>Guo, Yubin</creatorcontrib><creatorcontrib>Kopchick, John J</creatorcontrib><creatorcontrib>Kumar, Ujendra</creatorcontrib><creatorcontrib>Liu, Ye Lauren</creatorcontrib><title>Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice</title><title>American journal of physiology: endocrinology and metabolism</title><addtitle>Am J Physiol Endocrinol Metab</addtitle><description>1 Fraser Laboratories, Department of Medicine, and 3 Department of Surgery, McGill University, Montreal, Quebec H3A 1A1, Canada; and 2 Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopapthic Medicine, Ohio University, Athens, Ohio 45701 Submitted 22 September 2003 ; accepted in final form 5 May 2004 Growth hormone, acting through its receptor (GHR), plays an important role in carbohydrate metabolism and in promoting postnatal growth. GHR gene-deficient (GHR –/– ) mice exhibit severe growth retardation and proportionate dwarfism. To assess the physiological relevance of growth hormone actions, GHR –/– mice were used to investigate their phenotype in glucose metabolism and pancreatic islet function. Adult GHR –/– mice exhibited significant reductions in the levels of blood glucose and insulin, as well as insulin mRNA accumulation. Immunohistochemical analysis of pancreatic sections revealed normal distribution of the islets despite a significantly smaller size. The average size of the islets found in GHR –/– mice was only one-third of that in wild-type littermates. Total -cell mass was reduced 4.5-fold in GHR –/– mice, significantly more than their body size reduction. This reduction in pancreatic islet mass appears to be related to decreases in proliferation and cell growth. GHR –/– mice were different from the human Laron syndrome in serum insulin level, insulin responsiveness, and obesity. We conclude that growth hormone signaling is essential for maintaining pancreatic islet size, stimulating islet hormone production, and maintaining normal insulin sensitivity and glucose homeostasis. glucose homeostasis; immunohistochemistry; Laron syndrome; insulin tolerance test Address for reprint requests and other correspondence: J.-L. Liu, Fraser Laboratories, M3–15, Royal Victoria Hospital, 687 Pine Ave. West, Montreal, QC H3A 1A1, Canada (E-mail: jun-li.liu{at}mcgill.ca ).</description><subject>Animals</subject><subject>Blood Glucose - metabolism</subject><subject>Cell Division</subject><subject>Glucagon - blood</subject><subject>Glucose - metabolism</subject><subject>Growth Hormone - physiology</subject><subject>Homeostasis</subject><subject>Insulin - blood</subject><subject>Insulin - physiology</subject><subject>Islets of Langerhans - anatomy &amp; histology</subject><subject>Islets of Langerhans - growth &amp; development</subject><subject>Mice</subject><subject>Mice, Knockout - genetics</subject><subject>Obesity - genetics</subject><subject>Receptors, Somatotropin - genetics</subject><subject>Receptors, Somatotropin - physiology</subject><issn>0193-1849</issn><issn>1522-1555</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxS0EokvhC3BAPnHL4j9x4hxRaQGpEpe9W44z2UyVxMF2KFvx4fF2t-oJcfLY83tPnnmEvOdsy7kSn-zdAnPnt4yVQm4FY_IF2eSGKLhS6iXZMN7IguuyuSBvYrxjjNWqFK_JBVdcaq7khvz5gjGsS0I_U9_TffD3aaCDD5OfgQZwsCQf6B7yzdk1QqQdTjhjHKCji51dAJvQUYwjJBrxAaidO4qPjQjHKq4jzjTCHDHhL0yH_EYndPCWvOrtGOHd-bwku5vr3dW34vbH1-9Xn28LV-oyFWWn2qrRVpS6Al7XlRM9b_OIjPEeNHMWGg65YNLZum47qCqpW1Y65Zxr5CX5eLJdgv-5QkxmwuhgHO0Mfo2mqmotuGD_BQXPC5VMZlCcQBd8jAF6swScbDgYzswxG3POxjxmY47ZZNGHs_vaTtA9S85hZKA5AQPuh3sMYJbhENGPfn8wN-s47uB3enIWujbSXJdMmaXrs7b4t_bpM88a-Rc_tLQH</recordid><startdate>20040901</startdate><enddate>20040901</enddate><creator>Liu, Jun-Li</creator><creator>Coschigano, Karen T</creator><creator>Robertson, Katie</creator><creator>Lipsett, Mark</creator><creator>Guo, Yubin</creator><creator>Kopchick, John J</creator><creator>Kumar, Ujendra</creator><creator>Liu, Ye Lauren</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20040901</creationdate><title>Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice</title><author>Liu, Jun-Li ; Coschigano, Karen T ; Robertson, Katie ; Lipsett, Mark ; Guo, Yubin ; Kopchick, John J ; Kumar, Ujendra ; Liu, Ye Lauren</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c484t-4d5b698a2486e1776c2f1b555001fe80cae91ee8003ca77bde6638b04c5ccc93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Blood Glucose - metabolism</topic><topic>Cell Division</topic><topic>Glucagon - blood</topic><topic>Glucose - metabolism</topic><topic>Growth Hormone - physiology</topic><topic>Homeostasis</topic><topic>Insulin - blood</topic><topic>Insulin - physiology</topic><topic>Islets of Langerhans - anatomy &amp; histology</topic><topic>Islets of Langerhans - growth &amp; development</topic><topic>Mice</topic><topic>Mice, Knockout - genetics</topic><topic>Obesity - genetics</topic><topic>Receptors, Somatotropin - genetics</topic><topic>Receptors, Somatotropin - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Jun-Li</creatorcontrib><creatorcontrib>Coschigano, Karen T</creatorcontrib><creatorcontrib>Robertson, Katie</creatorcontrib><creatorcontrib>Lipsett, Mark</creatorcontrib><creatorcontrib>Guo, Yubin</creatorcontrib><creatorcontrib>Kopchick, John J</creatorcontrib><creatorcontrib>Kumar, Ujendra</creatorcontrib><creatorcontrib>Liu, Ye Lauren</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology: endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Jun-Li</au><au>Coschigano, Karen T</au><au>Robertson, Katie</au><au>Lipsett, Mark</au><au>Guo, Yubin</au><au>Kopchick, John J</au><au>Kumar, Ujendra</au><au>Liu, Ye Lauren</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice</atitle><jtitle>American journal of physiology: endocrinology and metabolism</jtitle><addtitle>Am J Physiol Endocrinol Metab</addtitle><date>2004-09-01</date><risdate>2004</risdate><volume>287</volume><issue>3</issue><spage>E405</spage><epage>E413</epage><pages>E405-E413</pages><issn>0193-1849</issn><eissn>1522-1555</eissn><abstract>1 Fraser Laboratories, Department of Medicine, and 3 Department of Surgery, McGill University, Montreal, Quebec H3A 1A1, Canada; and 2 Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopapthic Medicine, Ohio University, Athens, Ohio 45701 Submitted 22 September 2003 ; accepted in final form 5 May 2004 Growth hormone, acting through its receptor (GHR), plays an important role in carbohydrate metabolism and in promoting postnatal growth. GHR gene-deficient (GHR –/– ) mice exhibit severe growth retardation and proportionate dwarfism. To assess the physiological relevance of growth hormone actions, GHR –/– mice were used to investigate their phenotype in glucose metabolism and pancreatic islet function. Adult GHR –/– mice exhibited significant reductions in the levels of blood glucose and insulin, as well as insulin mRNA accumulation. Immunohistochemical analysis of pancreatic sections revealed normal distribution of the islets despite a significantly smaller size. The average size of the islets found in GHR –/– mice was only one-third of that in wild-type littermates. Total -cell mass was reduced 4.5-fold in GHR –/– mice, significantly more than their body size reduction. This reduction in pancreatic islet mass appears to be related to decreases in proliferation and cell growth. GHR –/– mice were different from the human Laron syndrome in serum insulin level, insulin responsiveness, and obesity. We conclude that growth hormone signaling is essential for maintaining pancreatic islet size, stimulating islet hormone production, and maintaining normal insulin sensitivity and glucose homeostasis. glucose homeostasis; immunohistochemistry; Laron syndrome; insulin tolerance test Address for reprint requests and other correspondence: J.-L. Liu, Fraser Laboratories, M3–15, Royal Victoria Hospital, 687 Pine Ave. West, Montreal, QC H3A 1A1, Canada (E-mail: jun-li.liu{at}mcgill.ca ).</abstract><cop>United States</cop><pmid>15138153</pmid><doi>10.1152/ajpendo.00423.2003</doi></addata></record>
fulltext fulltext
identifier ISSN: 0193-1849
ispartof American journal of physiology: endocrinology and metabolism, 2004-09, Vol.287 (3), p.E405-E413
issn 0193-1849
1522-1555
language eng
recordid cdi_pubmed_primary_15138153
source MEDLINE; American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects Animals
Blood Glucose - metabolism
Cell Division
Glucagon - blood
Glucose - metabolism
Growth Hormone - physiology
Homeostasis
Insulin - blood
Insulin - physiology
Islets of Langerhans - anatomy & histology
Islets of Langerhans - growth & development
Mice
Mice, Knockout - genetics
Obesity - genetics
Receptors, Somatotropin - genetics
Receptors, Somatotropin - physiology
title Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T04%3A43%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Disruption%20of%20growth%20hormone%20receptor%20gene%20causes%20diminished%20pancreatic%20islet%20size%20and%20increased%20insulin%20sensitivity%20in%20mice&rft.jtitle=American%20journal%20of%20physiology:%20endocrinology%20and%20metabolism&rft.au=Liu,%20Jun-Li&rft.date=2004-09-01&rft.volume=287&rft.issue=3&rft.spage=E405&rft.epage=E413&rft.pages=E405-E413&rft.issn=0193-1849&rft.eissn=1522-1555&rft_id=info:doi/10.1152/ajpendo.00423.2003&rft_dat=%3Cproquest_pubme%3E66782120%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=21193303&rft_id=info:pmid/15138153&rfr_iscdi=true