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Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack.
Physiol Rep. 2020 Jul; 8(13):e14444.PR

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.

Authors+Show Affiliations

Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Department of Medical Sciences, Uppsala University, Uppsala, Sweden.Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Lund, Sweden.Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32618430

Citation

Ullsten, Sara, et al. "Highly Blood Perfused, Highly Metabolically Active Pancreatic Islets May Be More Susceptible for Immune Attack." Physiological Reports, vol. 8, no. 13, 2020, pp. e14444.
Ullsten S, Espes D, Quach M, et al. Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack. Physiol Rep. 2020;8(13):e14444.
Ullsten, S., Espes, D., Quach, M., Fex, M., Sandberg, M., & Carlsson, P. O. (2020). Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack. Physiological Reports, 8(13), e14444. https://doi.org/10.14814/phy2.14444
Ullsten S, et al. Highly Blood Perfused, Highly Metabolically Active Pancreatic Islets May Be More Susceptible for Immune Attack. Physiol Rep. 2020;8(13):e14444. PubMed PMID: 32618430.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack. AU - Ullsten,Sara, AU - Espes,Daniel, AU - Quach,My, AU - Fex,Malin, AU - Sandberg,Monica, AU - Carlsson,Per-Ola, PY - 2020/02/28/received PY - 2020/04/22/revised PY - 2020/04/22/accepted PY - 2020/7/4/entrez PY - 2020/7/4/pubmed PY - 2020/7/4/medline KW - blood flow KW - heterogeneity KW - insulitis KW - pancreatic islets KW - type 1 diabetes SP - e14444 EP - e14444 JF - Physiological reports JO - Physiol Rep VL - 8 IS - 13 N2 - 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. SN - 2051-817X UR - https://www.unboundmedicine.com/medline/citation/32618430/Highly_blood_perfused,_highly_metabolically_active_pancreatic_islets_may_be_more_susceptible_for_immune_attack L2 - https://doi.org/10.14814/phy2.14444 DB - PRIME DP - Unbound Medicine ER -
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