Fetal pancreatic islets express functional leptin receptors and leptin stimulates proliferation of fetal islet cells.
OBJECTIVE
Previous studies have demonstrated that leptin can stimulate proliferation of insulin-secreting tumor cell lines. The objective of this study was to characterize whether leptin could stimulate proliferation of primary beta-cells too. Since adult beta-cells have very limited capacity for replication, we examined the effect of leptin on islets of Langerhans obtained from fetal rats, in a tissue culture system.


METHODS
Leptin receptor mRNA and c-fos mRNA were measured by RT-PCR. Proliferation of fetal rat islet cells was measured by a WST-1 colorimetric assay and [3H]-thymidine incorporation assay.


RESULTS
Leptin stimulated proliferation of serum-deprived fetal rat islet cells, as indicated by increased formation of formazan dye from a tetrazolium salt WST-1. Leptin stimulated DNA synthesis in islet cells, as indicated by increased [3H]-thymidine incorporation into DNA. The effect of leptin on islet cell proliferation was on average 39-50% of the effect obtained with 10% fetal bovine serum. Leptin increased c-fos mRNA expression by 2.8-fold in isolated fetal islets after 30 min treatment. In fetal pancreatic islets, both the common extracellular portion (OB-R) and the intact long form (OB-Rb) of the leptin receptor were readily detected by reverse transcriptase polymerase chain reaction.


CONCLUSIONS
Functional leptin receptors are expressed in pancreatic islet cells, as early as during the fetal stage of development of these microorgans. Leptin stimulates proliferation of fetal islet cells and might play a role in determining islet cell mass at birth.
Islam
M S
MS
Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden. Shahidul.Islam@molmed.ki.se
Sjöholm
A
A
Emilsson
V
V
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003124:Colorimetry; D046508:Culture Techniques; D005260:Female; D018507:Gene Expression Regulation, Developmental; D016762:Genes, fos / Q000235:genetics; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects* / Q000196:embryology* / Q000502:physiology; D020738:Leptin / Q000494:pharmacology* / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D002352:Carrier Proteins; C515448:LEPR protein, human; D020738:Leptin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin