Islets of Langerhans surrounded by a semipermeable membrane to prevent an immune response by the host immunosystem is a potential way of treating type I diabetes mellitus. In this study, poly(vinyl alcohol) (PVA) tubular membranes with added polyethylene glycol to create pores in the skin layer were prepared to improve their diffusion property. In a static incubation study, islets cultured in the PVA tubular membranes still demonstrated their function of secreting insulin after 30 days. When the tubular PVA bioartificial pancreas was perifused in a small chamber with RPMI-1640 medium containing glucose at concentrations of 5.6-16.6 mmol/L, insulin release began to increase without delay. Therefore, such a membrane is an alternative potential material for a bioartificial pancreas. In addition, a mathematical mass transfer model of insulin release was developed and compared with the perifusion data. It was shown that satisfactory kinetics could be achieved with a PVA membrane. However, the model showed that the insulin output of islets cultured in the PVA tubular membrane must be increased to improve the performance significantly. These findings suggest that a bioartificial pancreas using a PVA membrane is a promising material, but the technique for seeding islets in the chamber requires further modification.
How are the oscillatory insulin secretions from numerous islets synchronized to result in an identifiable oscillation? We postulated that a sudden increase in glucose concentration could best account for the interislet synchronization. The perifusion with two parallel chambers each containing 100 islets from the same rat was performed. The glucose concentrations of two chambers were simultaneously increased from 100 to 300 mg/dl in step function to examine the synchronizing efficacy. Synchrony and regularity of insulin oscillation were evaluated by cross-correlation and/or power spectral analysis. Although the insulin had been in stable oscillation, we found that the synchrony between two chambers and the regularity of each chamber were still significantly improved after a sudden increase in glucose level. However, the improved synchrony and regularity were transient. They gradually slid toward a less rigorous condition in a 15-h long-term perifusion. We suggested that the interislet synchronization of oscillatory insulin secretions could be improved by a sudden increase in glucose level. The insulin pulses were therefore enhanced to present their physiological effects.
Old donor age has been considered as a risk factor and relative contraindication for transplantation. This study was designed to investigate the influence of donor age on islet characteristics and transplantation. Islets isolated from 8 (I-A)-, 32 (I-B)-, or 64 (I-C)-week-old C57BL16 mice were studied for number, size, insulin content, and secretion. After syngeneically transplanting 300 islets under the kidney capsule of streptozotocin-diabetic mice (R-A. R-B, and R-C, respectively), we measured recipients' metabolic parameters as well as the beta-cell mass and insulin content of the graft. Eight-week-old donors had better glucose tolerance than 32- and 64-week-old donors. However, 64-week-old donors had more pancreatic insulin content than 8- and 32-week-old donors. I-B and I-C were greater in number, larger in size, and higher in insulin content than I-A. But perifusion study showed I-C secreted less insulin, albeit with a similar stimulation index compared with that of I-A and I-B. After transplantation, the fall of blood glucose in R-C was faster than that in R-A and R-B. At 12 weeks, the recipients' blood glucose, body weight, HbA1c, and the beta-cell mass and insulin content of the graft were comparable in all groups. However, R-C had better glucose tolerance than R-A. During follow-up, R-A and R-B maintained lifelong normoglycemia and their glucose tolerance did not deteriorate. These data indicate that islets isolated from donors with different ages have different characteristics and effects on transplantation. The islets isolated from aged donors are functioning well and can be a potential source for transplantation; however, because we transplanted a large islet mass from the aged donors, the role of the islet dose needs to be further clarified.
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