Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack
Abstract Differences in pancreatic islet susceptibility during type 1 diabetes development may be explained by interislet variations. This study aimed to investigate if heterogeneities in vascular support and metabolic activity in rat and human islets may explain why some islets are attacked earlier...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-07-01
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| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.14444 |
| _version_ | 1818259796126597120 |
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| author | Sara Ullsten Daniel Espes My Quach Malin Fex Monica Sandberg Per‐Ola Carlsson |
| author_facet | Sara Ullsten Daniel Espes My Quach Malin Fex Monica Sandberg Per‐Ola Carlsson |
| author_sort | Sara Ullsten |
| collection | DOAJ |
| description | Abstract Differences in pancreatic islet susceptibility during type 1 diabetes development may be explained by interislet variations. This study aimed to investigate if heterogeneities in vascular support and metabolic activity in rat and human islets may explain why some islets are attacked earlier than other islets. In rats, highly blood perfused islets were identified by injection of microspheres into the ascending aorta, whereas a combination of anterograde and retrograde injections of microspheres into pancreas was used to determine the islet vascular drainage system. Highly blood perfused islets had superior function and lower glucose threshold for insulin release when compared with other islets. These islets had a preferential direct venous drainage to the portal vein, whereas other islets mainly were incorporated into the exocrine capillary system. In BioBreeding rats, the hypothesis that islets with high islet blood perfusion was more prone to immune cell infiltration was investigated. Indeed, highly blood perfused islets were the first affected by the immune attack. In human subjects, differences in glucose threshold for insulin (C‐peptide) secretion was evaluated in individuals recently diagnosed for type 1 diabetes and compared to control subjects. A preferential loss of capacity for insulin release in response to low glucose concentrations was observed at debut of type 1 diabetes. Our study indicates that highly blood perfused islets with direct venous drainage and lower glucose threshold for insulin release are of great importance for normal glucose homeostasis. At the same time, these highly metabolically active islets were the primary target of the immune system. |
| first_indexed | 2024-12-12T18:21:08Z |
| format | Article |
| id | doaj.art-ce15c52f25ee49479ddc711bfd70cb45 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-12-12T18:21:08Z |
| publishDate | 2020-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-ce15c52f25ee49479ddc711bfd70cb452022-12-22T00:16:08ZengWileyPhysiological Reports2051-817X2020-07-01813n/an/a10.14814/phy2.14444Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attackSara Ullsten0Daniel Espes1My Quach2Malin Fex3Monica Sandberg4Per‐Ola Carlsson5Department of Medical Cell Biology Uppsala University Uppsala SwedenDepartment of Medical Cell Biology Uppsala University Uppsala SwedenDepartment of Medical Cell Biology Uppsala University Uppsala SwedenDepartment of Clinical Sciences Lund University Diabetes CenterLund University Lund SwedenDepartment of Medical Cell Biology Uppsala University Uppsala SwedenDepartment of Medical Cell Biology Uppsala University Uppsala SwedenAbstract Differences in pancreatic islet susceptibility during type 1 diabetes development may be explained by interislet variations. This study aimed to investigate if heterogeneities in vascular support and metabolic activity in rat and human islets may explain why some islets are attacked earlier than other islets. In rats, highly blood perfused islets were identified by injection of microspheres into the ascending aorta, whereas a combination of anterograde and retrograde injections of microspheres into pancreas was used to determine the islet vascular drainage system. Highly blood perfused islets had superior function and lower glucose threshold for insulin release when compared with other islets. These islets had a preferential direct venous drainage to the portal vein, whereas other islets mainly were incorporated into the exocrine capillary system. In BioBreeding rats, the hypothesis that islets with high islet blood perfusion was more prone to immune cell infiltration was investigated. Indeed, highly blood perfused islets were the first affected by the immune attack. In human subjects, differences in glucose threshold for insulin (C‐peptide) secretion was evaluated in individuals recently diagnosed for type 1 diabetes and compared to control subjects. A preferential loss of capacity for insulin release in response to low glucose concentrations was observed at debut of type 1 diabetes. Our study indicates that highly blood perfused islets with direct venous drainage and lower glucose threshold for insulin release are of great importance for normal glucose homeostasis. At the same time, these highly metabolically active islets were the primary target of the immune system.https://doi.org/10.14814/phy2.14444blood flowheterogeneityinsulitispancreatic isletstype 1 diabetes |
| spellingShingle | Sara Ullsten Daniel Espes My Quach Malin Fex Monica Sandberg Per‐Ola Carlsson Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack Physiological Reports blood flow heterogeneity insulitis pancreatic islets type 1 diabetes |
| title | Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack |
| title_full | Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack |
| title_fullStr | Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack |
| title_full_unstemmed | Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack |
| title_short | Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack |
| title_sort | highly blood perfused highly metabolically active pancreatic islets may be more susceptible for immune attack |
| topic | blood flow heterogeneity insulitis pancreatic islets type 1 diabetes |
| url | https://doi.org/10.14814/phy2.14444 |
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