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Abstract
Successful transplantation of fetal pancreatic β-cells to recipients with diabetes
requires that differentiation of the immature β-cells is induced. In this study isletlike
cell clusters (ICC) were produced from fetal porcine pancreas in tissue culture, in
medium RPMI-1640 supplemented with 10% human serum and in the presence or absence
of 10 mmol/L nicotinamide. Light microscopy of immunostained ICC on day 4 of culture
showed that nicotinamide caused a more than doubling in the frequency of insulin-positive
cells, whereas no stimulatory effect by nicotinamide on DNA replication was found.
Transplantation of ICC into nude mice with alloxan diabetes revealed that ICC formed
in nicotinamide normalized the hyperglycemia faster than did control ICC (3 to 4 weeks
compared with 6 to 8 weeks). The DNA content of the transplanted ICC increased two
to three times over an 8-week period, whereas the insulin content increased 100-fold.
The total insulin, total DNA content, and the insulin concentration of the grafts
were significantly higher in the nicotinamide grafts in comparison with control grafts.
In fact, the insulin concentration in the nicotinamide grafts was almost identical
to that normally observed in fully differentiated mouse islets. Furthermore, perfusion
in vitro of the graft-bearing kidneys 18 weeks after transplantation showed that the
total amount of insulin released from the nicotinamide grafts on stimulation with
glucose was more than five times higher than the amount from the control grafts. The
perfusion of grafts from the nicotinamide group revealed a marked biphasic insulin
response to glucose, which was less obvious in the control grafts. We conclude that
nicotinamide induces β-cell differentiation in porcine ICC and that this effect is
beneficial when such expiants are used for transplantation to recipients with diabetes.
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Article info
Publication history
Accepted:
October 4,
1991
Footnotes
☆Supported by grants from the Swedish Medical Research Council, the Swedish Diabetes Association, the Nordic Insulin Fund, the Aage-Louis Hansens Mindefond, the Swedish Society of Medicine, the Magnus Bergvall Foundation, the Torsten and Ragnar Söderberg Foundation, the Hoechst Diabetes Foundation, the Juvenile Diabetes Foundation International, the Family Ernfors Fund, the Wallenberg Fund, and the Swedish Society for Medical Research.
Identification
Copyright
© 1993 Published by Elsevier Inc.
