Effect of Endogenous Gastrin on Pancreatic Growth and Regeneration in Rat

Kim, Ki Hwan; Kim, Sun Whe; Park, Sang Jae; Her, Kyu Hee; Jang, Jin Young; Park, Yong Hyun

Abstract

PURPOSE: Gastrin is a candidate for the growth regulatory factors of the pancreas and may solve the problem of pancreatic atrophy after partial pancreatectomy. The purpose of this study was to evaluate the effect of endogenous gastrin on the normal growth and regeneration of the pancreas (after partial pancreatectomy) in rat. METHODS: Sixty Sprague-Dawley rats (200-230 g) were divided into 6 groups. Group (G)-I and II received sham operation (splenectomy only), and G-III, IV, V, VI received both 66% partial pancreatectomy (PPx) and splenectomy. Endogenous hypergastrinemia was induced in G-II, IV, VI by stomach gavage of 30 mg/kg.day of Lansoprozole (LSP) for 3 weeks. In G-V and VI, L365,260 (ML lab, UK) was given continuously in a dose of 50 microgram/kg/hour intraperitoneally using osmotic mini pump. The rats were sacrificed 3 weeks later, and serum gastrin, the weight and the amount of DNA, RNA, and protein in the remnant pancreas or corresponding part were checked. RESULTS: Serum gastrin concentration was 3-4 times higher in the groups received LSP. LSP stimulated growth of the pancreas (G-I: 11921 vs. G-II: 14220 mg/100 g body weight, p=0.047), and the effect was even greater in partial pancreatectomy groups (G-III: 14616 vs. G-IV: 17318 mg/100 g body weight, p=0.007). Total DNA, RNA, and protein amount in the remnant pancreas showed the same trends as the pancreas weight. The effect of LSP was totally abolished by L365,260 (G-V: 13517 vs. G-VI: 14313 mg/100 g body weight, p>0.047). CONCLUSION: Endogenous gastrin has a stimulatory effect on normal growth, and a much stronger effect on the regeneration of the rat pancreas after partial pancreatectomy. Further investigations including clinical trial should be needed.