Leptin increases the viability of isolated rat pancreatic islets by suppressing apoptosis.
To test the hypothesis that leptin secreted from adipose tissue is a mediator linking obesity and pancreatic islet hypertrophy, we examined the effects of leptin on proliferative and apoptotic responses in rat islet cells. Rat pancreatic islets were isolated and incubated with 0, 1, 5, or 75 nM leptin for 24 h under serum-deprived conditions. Cell viability was assessed with 2,5-diphenyltetrazolium bromide and trypan blue dye exclusion tests. Cell proliferation and apoptosis were evaluated with 5-bromo-2'-deoxyuridine incorporation into DNA and DNA ladder formation, respectively. Incubation for 24 h with 1 and 5 nM leptin, the concentrations observed in obese subjects, increased the viability of isolated pancreatic islet cells. Five nanomolar concentrations of leptin did not stimulate 5-bromo-2'-deoxyuridine incorporation into incubated islet cells, indicating no influence on cell proliferation, but did inhibit DNA ladder formation, a hallmark of cell apoptosis. Moreover, 5 nM leptin reduced the triglyceride content and suppressed inducible nitric oxide synthase mRNA expression in incubated islets. These results suggest that leptin increased viable cell numbers via suppression of apoptosis in isolated pancreatic islet cells under these experimental conditions. This mechanism might account at least in part for an obesity-induced increase in pancreatic beta-cell mass.
Okuya
S
S
Third Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan. okuya@po.cc.yamaguchi-u.ac.jp
Tanabe
K
K
Tanizawa
Y
Y
Oka
Y
Y
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014022:Tissue Survival / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism
D016895:Culture Media, Serum-Free; D020738:Leptin; D012333:RNA, Messenger; D014280:Triglycerides; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat