Effect of Leptin on Alteration of beta-cell Mass in Rat Pancreas

Hong, Seong Bin; Han, Yu Mi; Park, Young Ju; Oe, Yun Joo; Kim, Sung Ki; Kim, Yoe Joo; Nam, Moon Suk; Kim, Yong Seong; Park, In Sun

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.