Differences in blood perfusion correlates to pancreatic islet function in vitro

• Background and aims: The blood perfusion between different pancreatic islets varies considerably. In recent experiments we observe that this result in a markedly heterogenous oxygenation of the islets. The present study tested the hypothesis that heterogeneity between islets with regard to vascular support is also reflected in differences in islet beta-cell function. Materials and methods: Fluorescent microspheres (10 µm in size) were used to measure the blood perfusion of individual pancreatic islets in adult Wistar-Furth rats. Based on the microsphere distribution islets were separated into two groups, with blood flow below or above 0,4 µl/min. Functional studies of glucose-stimulated insulin release, insulin content and glucose oxidation rate were performed in vitro on freshly isolated islets. Gene expression studies were performed by RT-PCR. Vascular density quantification using two-photon confocal microscopy was performed separately for each group of islets after intravascular visualization of blood vessels by IB4 isolectin.Results: Functional studies on freshly isolated islets of the two groups revealed that islets with better blood perfusion had much higher basal and glucose-stimulated insulin release when compared to less perfused islets. No differences were observed between groups with regard to total insulin content, mitochondrial function, as assessed by studies of glucose oxidation rate, or in islet size. Vascular density quantification showed that approximately 10% of islets were composed of blood vessels in both groups, but that the vasculature in islets with lower blood perfusion had less tortuous architecture. Moreover, preliminary studies suggest that islets with better blood perfusion have higher gene expression of glucose transporter 2.Conclusion: Our results indicate that pancreatic islets with higher blood perfusion also have better function that remains after isolation of the islets. This may partially be explained by differences in vascular structure, but need to be further investigated.

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