EFFECTS OF NICOTINAMIDE SUPPLEMENTATION ON HUMAN PANCREATIC-ISLET FUNCTION IN TISSUE-CULTURE

Nicotinamide currently attracts considerable interest as a compound th at might prevent the development of human insulin-dependent diabetes m ellitus. The present study investigated the direct actions of nicotina mide on human pancreatic beta-cells. For this purpose, islets were iso lated from 11 adult cadaveric donors. The human islets were subsequent ly precultured in RPMI-1640 (5.6 mmol/L glucose) and 10% fetal calf se rum for 3-4 days. The islets were cultured for another 6 days in the s ame medium in either the presence or absence of 10 mmol/L nicotinamide , and subsequently, islet function was examined. After culture, both g roups of islets contained similar amounts of DNA, and DNA synthesis, d etermined by the tritiated thymidine incorporation rate, was unchanged . The insulin content both on a per islet basis and per DNA was simila r in both groups as was the islet glucose oxidation rate. Insulin accu mulation into the culture medium was sustained over the entire culture period and did not differ at any time point between the nicotinamide and the control group. Nicotinamide affected neither basal and glucose -stimulated insulin secretion nor (pro)insulin and total protein biosy nthesis rates after culture. The insulin response to glucose of the hu man islets was about 5-fold. In conclusion, the present study shows th at nicotinamide does not directly affect human beta-cell function or t he cell replicatory rate. This would suggest that any potential benefi cial effects observed after treatment with nicotinamide in patients wi th insulin-dependent diabetes mellitus may not necessarily reflect an action at the beta-cell level.