Decreased pancreatic acinar cell number in type 1 diabetes
Aims/hypothesis Individuals with longstanding and recent-onset type 1 diabetes have a smaller pancreas. Since beta cells represent a very small portion of the pancreas, the loss of pancreas volume in diabetes is primarily due to the loss of pancreatic exocrine mass. However, the structural changes i...
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| Veröffentlicht in: | Diabetologia 2020-07, Vol.63 (7), p.1418-1423 |
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| creator | Wright, Jordan J. Saunders, Diane C. Dai, Chunhua Poffenberger, Greg Cairns, Brynn Serreze, David V. Harlan, David M. Bottino, Rita Brissova, Marcela Powers, Alvin C. |
| description | Aims/hypothesis
Individuals with longstanding and recent-onset type 1 diabetes have a smaller pancreas. Since beta cells represent a very small portion of the pancreas, the loss of pancreas volume in diabetes is primarily due to the loss of pancreatic exocrine mass. However, the structural changes in the exocrine pancreas in diabetes are not well understood.
Methods
To characterise the pancreatic endocrine and exocrine compartments in diabetes, we studied pancreases from adult donors with type 1 diabetes compared with similarly aged donors without diabetes. Islet cell mass, islet morphometry, exocrine mass, acinar cell size and number and pancreas fibrosis were assessed by immunohistochemical staining. To better understand possible mechanisms of altered pancreas size, we measured pancreas size in three mouse models of insulin deficiency.
Results
Pancreases from donors with type 1 diabetes were approximately 45% smaller than those from donors without diabetes (47.4 ± 2.6 vs 85.7 ± 3.7 g), independent of diabetes duration or age of onset. Diabetic donor pancreases had decreased beta cell mass (0.061 ± 0.025 vs 0.94 ± 0.21 g) and reduced total exocrine mass (42.0 ± 4.9 vs 96.1 ± 6.5 g). Diabetic acinar cells were similar in size but fewer in number compared with those in pancreases from non-diabetic donors (63.7 ± 8.1 × 10
9
vs 121.6 ± 12.2 × 10
9
cells/pancreas), likely accounting for the difference in pancreas size. Within the type 1 diabetes exocrine tissue, there was a greater degree of fibrosis. The pancreases in three mouse models of insulin deficiency were similar in size to those in control mice.
Conclusions/interpretation
Pancreases from donors with type 1 diabetes are smaller than normal donor pancreases because exocrine cells are fewer in number rather than smaller in size; these changes occur early in the disease process. Our mouse data suggest that decreased pancreas size in type 1 diabetes is not directly caused by insulin deficiency, but the precise mechanism responsible remains unclear. |
| doi_str_mv | 10.1007/s00125-020-05155-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8403487</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2401125398</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-c4a1508712e9081374b11157e3fb9ca892124525c986a7e324eb7f7506fffcd53</originalsourceid><addsrcrecordid>eNp9kUtLxDAQx4Mouj6-gAcpePFSncljm3oQZH2C4EXBW0izU63spmvSCvvtzbq-DxJIhsxv_snMn7FdhEMEKI4iAHKVA4ccFCqVz1fYAKXgOUiuV9lgkc9RDx822GaMzwAglByusw3Bhdaq5AN2fEYukI00zmbWL8KucZl1jbchczSZZL6fVhSyxmfdfEYZZuPGVtRR3GZrtZ1E2vk4t9j9xfnd6Cq_ub28Hp3e5E4Wsku7RQW6QE4laBSFrBBRFSTqqnRWlxy5VFy5Ug9tuuWSqqIuFAzrunZjJbbYyVJ31ldTGjvyXbATMwvN1Ia5aW1jfmd882Qe21ejJQipiyRw8CEQ2peeYmemTVz0Zj21fTRcAqZBilIndP8P-tz2waf2EoVptmnJRPEl5UIbY6D66zMIZmGNWVpjkjXm3RozT0V7P9v4Kvn0IgFiCcSU8o8Uvt_-R_YNAZOYoA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2411434344</pqid></control><display><type>article</type><title>Decreased pancreatic acinar cell number in type 1 diabetes</title><source>SpringerLink Journals - AutoHoldings</source><creator>Wright, Jordan J. ; Saunders, Diane C. ; Dai, Chunhua ; Poffenberger, Greg ; Cairns, Brynn ; Serreze, David V. ; Harlan, David M. ; Bottino, Rita ; Brissova, Marcela ; Powers, Alvin C.</creator><creatorcontrib>Wright, Jordan J. ; Saunders, Diane C. ; Dai, Chunhua ; Poffenberger, Greg ; Cairns, Brynn ; Serreze, David V. ; Harlan, David M. ; Bottino, Rita ; Brissova, Marcela ; Powers, Alvin C.</creatorcontrib><description>Aims/hypothesis
Individuals with longstanding and recent-onset type 1 diabetes have a smaller pancreas. Since beta cells represent a very small portion of the pancreas, the loss of pancreas volume in diabetes is primarily due to the loss of pancreatic exocrine mass. However, the structural changes in the exocrine pancreas in diabetes are not well understood.
Methods
To characterise the pancreatic endocrine and exocrine compartments in diabetes, we studied pancreases from adult donors with type 1 diabetes compared with similarly aged donors without diabetes. Islet cell mass, islet morphometry, exocrine mass, acinar cell size and number and pancreas fibrosis were assessed by immunohistochemical staining. To better understand possible mechanisms of altered pancreas size, we measured pancreas size in three mouse models of insulin deficiency.
Results
Pancreases from donors with type 1 diabetes were approximately 45% smaller than those from donors without diabetes (47.4 ± 2.6 vs 85.7 ± 3.7 g), independent of diabetes duration or age of onset. Diabetic donor pancreases had decreased beta cell mass (0.061 ± 0.025 vs 0.94 ± 0.21 g) and reduced total exocrine mass (42.0 ± 4.9 vs 96.1 ± 6.5 g). Diabetic acinar cells were similar in size but fewer in number compared with those in pancreases from non-diabetic donors (63.7 ± 8.1 × 10
9
vs 121.6 ± 12.2 × 10
9
cells/pancreas), likely accounting for the difference in pancreas size. Within the type 1 diabetes exocrine tissue, there was a greater degree of fibrosis. The pancreases in three mouse models of insulin deficiency were similar in size to those in control mice.
Conclusions/interpretation
Pancreases from donors with type 1 diabetes are smaller than normal donor pancreases because exocrine cells are fewer in number rather than smaller in size; these changes occur early in the disease process. Our mouse data suggest that decreased pancreas size in type 1 diabetes is not directly caused by insulin deficiency, but the precise mechanism responsible remains unclear.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-020-05155-y</identifier><identifier>PMID: 32388592</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Acinar cells ; Animal models ; Beta cells ; Cell number ; Cell size ; Diabetes ; Diabetes mellitus (insulin dependent) ; Fibrosis ; Human Physiology ; Insulin ; Internal Medicine ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Morphometry ; Pancreas ; Short Communication</subject><ispartof>Diabetologia, 2020-07, Vol.63 (7), p.1418-1423</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-c4a1508712e9081374b11157e3fb9ca892124525c986a7e324eb7f7506fffcd53</citedby><cites>FETCH-LOGICAL-c474t-c4a1508712e9081374b11157e3fb9ca892124525c986a7e324eb7f7506fffcd53</cites><orcidid>0000-0002-4999-3280 ; 0000-0003-1540-2996 ; 0000-0002-8849-6746 ; 0000-0002-6938-8109 ; 0000-0002-2043-0150 ; 0000-0003-1941-5786</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-020-05155-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-020-05155-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32388592$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wright, Jordan J.</creatorcontrib><creatorcontrib>Saunders, Diane C.</creatorcontrib><creatorcontrib>Dai, Chunhua</creatorcontrib><creatorcontrib>Poffenberger, Greg</creatorcontrib><creatorcontrib>Cairns, Brynn</creatorcontrib><creatorcontrib>Serreze, David V.</creatorcontrib><creatorcontrib>Harlan, David M.</creatorcontrib><creatorcontrib>Bottino, Rita</creatorcontrib><creatorcontrib>Brissova, Marcela</creatorcontrib><creatorcontrib>Powers, Alvin C.</creatorcontrib><title>Decreased pancreatic acinar cell number in type 1 diabetes</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
Individuals with longstanding and recent-onset type 1 diabetes have a smaller pancreas. Since beta cells represent a very small portion of the pancreas, the loss of pancreas volume in diabetes is primarily due to the loss of pancreatic exocrine mass. However, the structural changes in the exocrine pancreas in diabetes are not well understood.
Methods
To characterise the pancreatic endocrine and exocrine compartments in diabetes, we studied pancreases from adult donors with type 1 diabetes compared with similarly aged donors without diabetes. Islet cell mass, islet morphometry, exocrine mass, acinar cell size and number and pancreas fibrosis were assessed by immunohistochemical staining. To better understand possible mechanisms of altered pancreas size, we measured pancreas size in three mouse models of insulin deficiency.
Results
Pancreases from donors with type 1 diabetes were approximately 45% smaller than those from donors without diabetes (47.4 ± 2.6 vs 85.7 ± 3.7 g), independent of diabetes duration or age of onset. Diabetic donor pancreases had decreased beta cell mass (0.061 ± 0.025 vs 0.94 ± 0.21 g) and reduced total exocrine mass (42.0 ± 4.9 vs 96.1 ± 6.5 g). Diabetic acinar cells were similar in size but fewer in number compared with those in pancreases from non-diabetic donors (63.7 ± 8.1 × 10
9
vs 121.6 ± 12.2 × 10
9
cells/pancreas), likely accounting for the difference in pancreas size. Within the type 1 diabetes exocrine tissue, there was a greater degree of fibrosis. The pancreases in three mouse models of insulin deficiency were similar in size to those in control mice.
Conclusions/interpretation
Pancreases from donors with type 1 diabetes are smaller than normal donor pancreases because exocrine cells are fewer in number rather than smaller in size; these changes occur early in the disease process. Our mouse data suggest that decreased pancreas size in type 1 diabetes is not directly caused by insulin deficiency, but the precise mechanism responsible remains unclear.</description><subject>Acinar cells</subject><subject>Animal models</subject><subject>Beta cells</subject><subject>Cell number</subject><subject>Cell size</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Fibrosis</subject><subject>Human Physiology</subject><subject>Insulin</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Morphometry</subject><subject>Pancreas</subject><subject>Short Communication</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kUtLxDAQx4Mouj6-gAcpePFSncljm3oQZH2C4EXBW0izU63spmvSCvvtzbq-DxJIhsxv_snMn7FdhEMEKI4iAHKVA4ccFCqVz1fYAKXgOUiuV9lgkc9RDx822GaMzwAglByusw3Bhdaq5AN2fEYukI00zmbWL8KucZl1jbchczSZZL6fVhSyxmfdfEYZZuPGVtRR3GZrtZ1E2vk4t9j9xfnd6Cq_ub28Hp3e5E4Wsku7RQW6QE4laBSFrBBRFSTqqnRWlxy5VFy5Ug9tuuWSqqIuFAzrunZjJbbYyVJ31ldTGjvyXbATMwvN1Ia5aW1jfmd882Qe21ejJQipiyRw8CEQ2peeYmemTVz0Zj21fTRcAqZBilIndP8P-tz2waf2EoVptmnJRPEl5UIbY6D66zMIZmGNWVpjkjXm3RozT0V7P9v4Kvn0IgFiCcSU8o8Uvt_-R_YNAZOYoA</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Wright, Jordan J.</creator><creator>Saunders, Diane C.</creator><creator>Dai, Chunhua</creator><creator>Poffenberger, Greg</creator><creator>Cairns, Brynn</creator><creator>Serreze, David V.</creator><creator>Harlan, David M.</creator><creator>Bottino, Rita</creator><creator>Brissova, Marcela</creator><creator>Powers, Alvin C.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4999-3280</orcidid><orcidid>https://orcid.org/0000-0003-1540-2996</orcidid><orcidid>https://orcid.org/0000-0002-8849-6746</orcidid><orcidid>https://orcid.org/0000-0002-6938-8109</orcidid><orcidid>https://orcid.org/0000-0002-2043-0150</orcidid><orcidid>https://orcid.org/0000-0003-1941-5786</orcidid></search><sort><creationdate>20200701</creationdate><title>Decreased pancreatic acinar cell number in type 1 diabetes</title><author>Wright, Jordan J. ; Saunders, Diane C. ; Dai, Chunhua ; Poffenberger, Greg ; Cairns, Brynn ; Serreze, David V. ; Harlan, David M. ; Bottino, Rita ; Brissova, Marcela ; Powers, Alvin C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-c4a1508712e9081374b11157e3fb9ca892124525c986a7e324eb7f7506fffcd53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acinar cells</topic><topic>Animal models</topic><topic>Beta cells</topic><topic>Cell number</topic><topic>Cell size</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Fibrosis</topic><topic>Human Physiology</topic><topic>Insulin</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Morphometry</topic><topic>Pancreas</topic><topic>Short Communication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wright, Jordan J.</creatorcontrib><creatorcontrib>Saunders, Diane C.</creatorcontrib><creatorcontrib>Dai, Chunhua</creatorcontrib><creatorcontrib>Poffenberger, Greg</creatorcontrib><creatorcontrib>Cairns, Brynn</creatorcontrib><creatorcontrib>Serreze, David V.</creatorcontrib><creatorcontrib>Harlan, David M.</creatorcontrib><creatorcontrib>Bottino, Rita</creatorcontrib><creatorcontrib>Brissova, Marcela</creatorcontrib><creatorcontrib>Powers, Alvin C.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wright, Jordan J.</au><au>Saunders, Diane C.</au><au>Dai, Chunhua</au><au>Poffenberger, Greg</au><au>Cairns, Brynn</au><au>Serreze, David V.</au><au>Harlan, David M.</au><au>Bottino, Rita</au><au>Brissova, Marcela</au><au>Powers, Alvin C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased pancreatic acinar cell number in type 1 diabetes</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>63</volume><issue>7</issue><spage>1418</spage><epage>1423</epage><pages>1418-1423</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
Individuals with longstanding and recent-onset type 1 diabetes have a smaller pancreas. Since beta cells represent a very small portion of the pancreas, the loss of pancreas volume in diabetes is primarily due to the loss of pancreatic exocrine mass. However, the structural changes in the exocrine pancreas in diabetes are not well understood.
Methods
To characterise the pancreatic endocrine and exocrine compartments in diabetes, we studied pancreases from adult donors with type 1 diabetes compared with similarly aged donors without diabetes. Islet cell mass, islet morphometry, exocrine mass, acinar cell size and number and pancreas fibrosis were assessed by immunohistochemical staining. To better understand possible mechanisms of altered pancreas size, we measured pancreas size in three mouse models of insulin deficiency.
Results
Pancreases from donors with type 1 diabetes were approximately 45% smaller than those from donors without diabetes (47.4 ± 2.6 vs 85.7 ± 3.7 g), independent of diabetes duration or age of onset. Diabetic donor pancreases had decreased beta cell mass (0.061 ± 0.025 vs 0.94 ± 0.21 g) and reduced total exocrine mass (42.0 ± 4.9 vs 96.1 ± 6.5 g). Diabetic acinar cells were similar in size but fewer in number compared with those in pancreases from non-diabetic donors (63.7 ± 8.1 × 10
9
vs 121.6 ± 12.2 × 10
9
cells/pancreas), likely accounting for the difference in pancreas size. Within the type 1 diabetes exocrine tissue, there was a greater degree of fibrosis. The pancreases in three mouse models of insulin deficiency were similar in size to those in control mice.
Conclusions/interpretation
Pancreases from donors with type 1 diabetes are smaller than normal donor pancreases because exocrine cells are fewer in number rather than smaller in size; these changes occur early in the disease process. Our mouse data suggest that decreased pancreas size in type 1 diabetes is not directly caused by insulin deficiency, but the precise mechanism responsible remains unclear.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32388592</pmid><doi>10.1007/s00125-020-05155-y</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-4999-3280</orcidid><orcidid>https://orcid.org/0000-0003-1540-2996</orcidid><orcidid>https://orcid.org/0000-0002-8849-6746</orcidid><orcidid>https://orcid.org/0000-0002-6938-8109</orcidid><orcidid>https://orcid.org/0000-0002-2043-0150</orcidid><orcidid>https://orcid.org/0000-0003-1941-5786</orcidid><oa>free_for_read</oa></addata></record> |
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| source | SpringerLink Journals - AutoHoldings |
| subjects | Acinar cells Animal models Beta cells Cell number Cell size Diabetes Diabetes mellitus (insulin dependent) Fibrosis Human Physiology Insulin Internal Medicine Medicine Medicine & Public Health Metabolic Diseases Morphometry Pancreas Short Communication |
| title | Decreased pancreatic acinar cell number in type 1 diabetes |
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