Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion

• Published in: Diabetologia Vol. 55; no. 5; pp. 1390 - 1399
• Main Authors: Lau, J., Svensson, J., Grapensparr, L., Johansson, Å., Carlsson, P.-O.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.05.2012; Springer; Springer Nature B.V
• Subjects: Animals; Aorta; Beta cell function; Beta cell growth; Beta cells; Biological and medical sciences; Blood vessels; Cell growth; Cell Proliferation; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelial cells; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fluorescent Dyes - administration & dosage; Gene expression; Gene Expression - physiology; Glucagon; Glucose; Human Physiology; Hypotheses; Insulin; Insulin-Secreting Cells - physiology; Internal Medicine; Islets of Langerhans; Islets of Langerhans - blood supply; Laboratory animals; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Microspheres; Pancreas; Pancreatic islets; Perfusion; Rats; Rats, Inbred WF; Vascular endothelial growth factor; Vascularised islets; United States > US; Sweden; Beta cell function; Pancreatic islets; Beta cell growth; Vascularised islets; Endocrinopathy; Cell proliferation; Rat; Growth; Diabetes mellitus; Langerhans islet; Rodentia; Gene expression; Vertebrata; Mammalia; Animal; β Cell; Endocrine pancreas
• ISSN: 0012-186X; 1432-0428; 1432-0428
• DOI: 10.1007/s00125-012-2476-6

Aims/hypothesis The blood perfusion of individual pancreatic islets is highly variable, with a subgroup of islets having high perfusion and blood vessels responsive to further blood flow increase induced by glucose. This study tested the hypothesis that there is heterogeneity between islets with regard to beta cell proliferation, function and gene expression based on differences in their blood perfusion. Methods Fluorescent microspheres were injected into the ascending aorta, and then microsphere-containing and non-microsphere-containing pancreatic islets were isolated for investigation. By this procedure, the 5% of islets with the greatest blood perfusion were identified for study. Islet endothelial cells were isolated separately to investigate the role of improved vascular support in the observed differences. Results The vascular network was found to be more dense and tortuous in microsphere-containing than other islets. The most highly blood-perfused islets also had a higher rate of beta cell proliferation, superior beta cell function and a markedly different gene expression from other islets. Cultured islets exposed to islet endothelial cell products had a similarly increased beta cell proliferation rate, yet significantly fewer changes in gene expression than observed in the most highly blood-perfused islets. Conclusions/interpretation A novel heterogeneity between islets was observed, with superior beta cell proliferation, function and gene expression in a subpopulation of islets identified by high blood perfusion. In contrast with a previously described population of low-oxygenated, sleeping islets, which are recruited into functionality when needed, the presently described heterogeneity is shown to remain in vitro after islet isolation.