Abstract
The blood perfusion of pancreatic islets is regulated independently from that of the exocrine pancreas, and is of importance for multiple aspects of normal islet function, and probably also during impaired glucose tolerance. Single islet blood flow has been difficult to evaluate due to technical limitations. We therefore adapted a hydrogen gas washout technique using microelectrodes to allow such measurements. Platinum micro-electrodes monitored hydrogen gas clearance from individual endogenous and transplanted islets in the pancreas of male Lewis rats and in human and mouse islets implanted under the renal capsule of male athymic mice. Both in the rat endogenous pancreatic islets as well as in the intra-pancreatically transplanted islets, the vascular conductance and blood flow values displayed a highly heterogeneous distribution, varying by factors 6–10 within the same pancreas. The blood flow of human and mouse islet grafts transplanted in athymic mice was approximately 30% lower than that in the surrounding renal parenchyma. The present technique provides unique opportunities to study the islet vascular dysfunction seen after transplantation, but also allows for investigating the effects of genetic and environmental perturbations on islet blood flow at the single islet level in vivo.
Highlights
Pancreatic islet blood perfusion has attracted increasing attention during the last decades (Jansson and Carlsson, 2002; Lammert, 2008)
The microsphere technique has been considered for decades to be the “gold-standard” for blood flow measurements in general (Prinzen and Bassingthwaighte, 2000) and its limitations and advantages when applied to islet blood flow have been discussed in detail (Jansson and Hellerström, 1983; Lifson et al, 1980)
The rats were allowed to recover from anesthesia, and were kept single in cages for 7 days after which some of the animals were transplanted and all were kept for another 4 weeks before being studied with hydrogen gas washout or the microsphere technique
Summary
Pancreatic islet blood perfusion has attracted increasing attention during the last decades (Jansson and Carlsson, 2002; Lammert, 2008). Islet vasculature has been shown to possess morphological and functional qualities making it uniquely adapted to the functional needs of this complex endocrine organ. It plays key roles in islet development and growth as well as immunological and inflammatory reactions within the islets (Johansson et al, 2006a; Olerud et al, 2011). The microsphere technique has been considered for decades to be the “gold-standard” for blood flow measurements in general (Prinzen and Bassingthwaighte, 2000) and its limitations and advantages when applied to islet blood flow have been discussed in detail (Jansson and Hellerström, 1983; Lifson et al, 1980).
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