Abstract

BACKGROUND
Diabetes mellitus can occur when insulin secretion and action are inadequate in relation to blood glucose level. Several experiments recently reported that leptin and pancreatic beta-cells have functional axis to interact each other. The present study was aimed to investigate the role of leptin on regulation of beta-cell mass during neonatal period when they show a dynamic growth. METHOD: Leptin was injected intraperitoneally to rat neonates for 7 days from the second day after birth. Using the pancreas of the rat pups, immunohistochemical stain, in-situ hybridization and northern blot for insulin were done for analysis of beta-cell mass as well as for insulin synthesis and secretion. In addition, PCNA (proliferating cell nuclear antigen) was examined to assess the effect of leptin on islet cell proliferation. RESULT: 1) The weight gain and blood glucose levels showed no significant difference between leptin injected groups (0.1 mg/kg, 0.5 mg/kg) and control one. 2) The weights of pancreas were not different between both group. 3) Pancreatic islets of rat who received leptin 0.5 mg/kg were reduced in area and number than those of normal pups. They also showed the decreased beta-cell number per islet compared with control as well as leptin 0.1 mg/kg injected groups (59+/-49 vs 47+/-31 vs 31+/-21 per islet, p<0.05). 4) The beta-cell mass of rat who received leptin 0.5 mg/kg decreased but there was no significant difference. 5) The mRNA expressions of insulin were not different among control, leptin 0.1 mg/kg and leptin 0.5 mg/kg group. 6) The expression of PCNA as a proliferation marker showed no difference between control and leptin injected group. CONCLUSION: These results reflected that leptin negatively regulated neonatal islet cell growth occurring in normal rat pups, and resulted to relative decrease of beta-cell number compared to the untreated control. We, therefore, suggest that leptin may play the important role in beta-cell mass during neonatal period.

• Keywords: Leptin;beta cell;Insulin