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

Abstract

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 nonmicrosphere-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.

Serotonin competence of mouse beta cells during pregnancy

“…Another possible local effect is that islet blood flow is regulated by pregnancy-induced serotonin production. This merits further investigation as serotonin is known to have potent vasoconstricting effects [39] and because pancreatic islets are known to have a very high local blood flow that may underlie part of the functional heterogeneity between islets [40]. Previous studies of blood flow in islets of pregnant rats demonstrated that islet blood flow was increased at day 15 of pregnancy but decreased at day 18 of pregnancy [30].…”

Vascular heterogeneity between native rat pancreatic islets is responsible for differences in survival and revascularisation post transplantation

“…The present study shows that the previously described pool of highly functional, highly blood-perfused islets in the native pancreas [9] has a higher susceptibility to cellular stress with Microsphere-containing islets (c) regained a higher vascular density than non-microsphere-containing islets (b) post transplantation; insulin is shown in brown, endothelial cells in red; scale bar, 50 μm. Values are given as means ± SEM for six islet grafts of microsphere-or nonmicrosphere-containing islets, respectively.…”

“…A low-oxygenated proportion of islets were found to be a resting or dormant population, which at increased metabolic demands could be activated and manifested as an increase in oxygen support [10]. Islets that in the native pancreas are highly blood-perfused were on the other hand observed to be the most functionally active, with higher glucose-stimulated insulin release, higher beta cell proliferation and a different gene expression in comparison with size-matched control islets [9].…”

“…Heterogeneities ranging from subpopulations of differently metabolically active beta cells to islet and pancreatic regional heterogeneities have been described [9][10][11][12][13][14]. Beta cells are also heterogeneous in their capabilities for production of the vasoactive factor serotonin during pregnancy [15].…”

Cocaine- and amphetamine-regulated transcript: a novel regulator of energy homeostasis expressed in a subpopulation of pancreatic islet cells

“…The reasons for this heterogeneity are unknown but this situation is reminiscent of the variability of placental lactogen-induced serotonin immunoreactivity in individual beta cells [26,27], and of the variability in glucose responsiveness of individual beta cells [28,29]. Heterogeneity of proliferation, gene expression and the function of beta cells between islets as a result of differential blood flow has also been documented in the rat [30]. It is possible that glycaemia is a direct regulator of CART…”