Fetal pancreatic islets express functional leptin receptors and leptin stimulates proliferation of fetal islet cells

OBJECTIVE: Previous studies have demonstrated that leptin can stimulate pro liferation of insulin-secreting tumor cell lines. The objective of this stu dy was to characterize whether leptin could stimulate proliferation of prim ary beta-cells too. Since adult beta-cells have very limited capacity for r eplication, we examined the effect of leptin on islets of Langerhans obtain ed from fetal rats, in a tissue culture system. METHODS: Leptin receptor mRNA and c-fos mRNA were measured by RT-PCR, Proli feration of fetal rat islet cells was measured by a WST-1 colorimetric assa y and [H-3]-thymidine incorporation assay. RESULTS: Leptin stimulated proliferation of serum-deprived fetal rat islet cells, as indicated by increased formation of formazan dye from a tetrazoli um salt WST-1. Leptin stimulated DNA synthesis in islet cells, as indicated by increased [H-3]-thymidine incorporation into DNA. The effect of leptin on islet cell proliferation was on average 39-50% of the effect obtained wi th 10% fetal bovine serum. Leptin increased c-fos mRNA expression by 2.8-fo ld in isolated fetal islets after 30 min treatment. In fetal pancreatic isl ets, both the common extracellular portion (OB-R) and the intact long form (OB-Rb) of the leptin receptor were readily detected by reverse transcripta se polymerase chain reaction, CONCLUSION: Functional leptin receptors are expressed in pancreatic islet c ells, as early as during the fetal stage of development of these microorgan s. Leptin stimulates proliferation of fetal islet cells and might play a ro le in determining islet cell mass at birth.