To test the hypothesis that leptin secreted from adipose tissue is a mediat
or linking obesity and pancreatic islet hypertrophy, we examined the effect
s of leptin on proliferative and apoptotic responses in rat islet cells. Ra
t pancreatic islets were isolated and incubated with 0, 1, 5, or 75 nM lept
in for 24 h under serum-deprived conditions. Cell viability was assessed wi
th 2,5-diphenyltetrazolium bromide and trypan blue dye exclusion tests. Cel
l proliferation and apoptosis were evaluated with 5-bromo-2'-deoxyuridine i
ncorporation into DNA and DNA ladder formation, respectively. Incubation fo
r 24 h with 1 and 5 lam leptin, the concentrations observed in obese subjec
ts, increased the viability of isolated pancreatic islet cells. Five nanomo
lar concentrations of leptin did not stimulate 5-bromo-2'-deoxyuridine inco
rporation into incubated islet cells, indicating no influence on cell proli
feration, but did inhibit DNA ladder formation, a hallmark of cell apoptosi
s. Moreover, 5 nm leptin reduced the triglyceride content and suppressed in
ducible nitric oxide synthase mRNA expression in incubated islets. These re
sults suggest that leptin increased viable cell numbers via suppression of
apoptosis in isolated pancreatic islet cells under these experimental condi
tions. This mechanism might account at least in part for an obesity-induced
increase in pancreatic P-cell mass.