Highly blood perfused, highly metabolically active pancreatic islets may be more susceptible for immune attack

• Published in: Physiological reports Vol. 8; no. 13; pp. e14444 - n/a
• Main Authors: Ullsten, Sara, Espes, Daniel, Quach, My, Fex, Malin, Sandberg, Monica, Carlsson, Per‐Ola
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.07.2020; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Anterograde transport; Aorta; Blood; blood flow; Blood Glucose - metabolism; Carotid arteries; Catheters; Cells, Cultured; Clinical Medicine; Coronary vessels; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - physiopathology; Endocrinology and Diabetes; Endokrinologi och diabetes; Glucose; heterogeneity; Homeostasis; Hypotheses; Immune system; Insulin; Insulin - metabolism; Insulin Secretion; insulitis; Islets of Langerhans - blood supply; Islets of Langerhans - immunology; Islets of Langerhans - metabolism; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Microspheres; Original Research; Pancreas; pancreatic islets; Perfusion; Polyethylene; Portal vein; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Retrograde transport; type 1 diabetes; Veins & arteries; Wound drainage; type 1 diabetes; insulitis; blood flow; heterogeneity; pancreatic islets
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.14444

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. Highly blood perfused islets with their direct venous drainage and lower glucose threshold for insulin release seem to be of great importance for normal glucose homeostasis. At the same time, these highly metabolically active islets are the primary target of the immune system which may explain why some islets are attacked earlier than other islets during the development of type 1 diabetes.