Effects of aging on the regenerative capacity of the pancreatic B-cell of the rat.
Since an increased insulin resistance could be expected to lead to a compensatory B-cell hyperplasia, it may be speculated that human type II diabetes becomes manifest only in those individuals who are unable to respond to an increased insulin demand with a higher rate of B-cell proliferation. To test this hypothesis experimentally, the cell cycle and growth regulation of the pancreatic B cell has been studied in vitro. Islets of fetal, 1-wk, 3-wk, and 3-mo-old rats were isolated and maintained in tissue culture at different glucose concentrations. The proliferating islet cells were synchronized with hydroxyurea and their progression through the cell cycle studied by pulse labeling with 3H-thymidine. From the cell cycle data it was possible to calculate the rate of formation of new B-cells. The cell cycle of the B-cells was similar in all donor age groups. When the glucose concentration of the culture medium was raised from 2.7 to 16.7 mM, the rate of B-cell proliferation increased 2.5-fold in all age groups, but there was no further increase in proliferation at 33.3 mM. At each of the glucose concentrations tested the rate of B-cell formation decreased with increasing age of the donor. Results indicate that only a fraction of the islet cells are capable of entering the cell cycle and undergoing mitosis. This fraction composed about 10% of the fetal islet cells but was less than 3% in the adult islets. The small pool of proliferating cells in adult islets could explain why B-cell multiplication, although present in the aging rat, is insufficient to increase the insulin output to levels at which normal glucose tolerance is maintained. This forms an interesting parallel to the development of type II diabetes in man, in which an inherited low capacity for B-cell regeneration may predispose to the disease.
D000375:Aging; D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D003920:Diabetes Mellitus / Q000209:etiology; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D004247:DNA