Leptin increases the viability of isolated rat pancreatic islets by suppressing apoptosis

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.