Functional Response of a Limited βCell Mass to LongTerm Hyperglycemia

Autor: Dunger, A., Kauert, C., Brömme, H. J., Hildebrandt, W., Blech, W., Hahn, H. J.
Zdroj: Pancreas; March 1994, Vol. 9 Issue: 2 p186-192, 7p
Abstrakt: 250 syngeneic islets were implanted either beneath the kidney capsule or into the liver of diabetic LEW l.A rats to investigate the functional response of a limited mass of p-cells to long-term hyperglycemia. The number of islets, per se, was expected to be insufficient to reverse the hyperglycemia. All animals were characterized by a substantial body weight gain. Unexpectedly, 29 of the rats with a subrenal and 40 of the animals with a portal islet graft normalized their plasma glucose in 64 ± 13 and 75 ± 12 days, respectively. Depending on the glycemic state of the recipients, there was an elevation of the graft insulin content after 120 days over the level at transplantation. The responsiveness of the implanted islets to different secretagogues was tested either in vitro by static incubation of the prepared grafts from the kidney or in situ by perfusion of the islet-containing liver. Grafts of normoglycemic rats showed a pronounced response, although the biphasic profile of the hormone release was lost. In principle, grafts exposed permanently to a hyper-glycemic environment have kept their responsiveness, although the insulin outflow was considerably lower. The functional viability of the islets was not influenced by the site of transplantation. Long-term hyperglycemia does not necessarily result in destruction and loss of p-cells even when their total mass is already limited, but it obviously impairs their functional responsiveness.
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