Role of ghrelin in the pancreatic exocrine secretion via mitogen-activated protein kinase signaling in rats

生长素释放肽通过丝裂原活化蛋白激酶信号在大鼠胰腺外分泌中的作用

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作者:Kyung-Hoon Lee #, Jae-Sung Lee #, Tao Wang, Jin-Ju Oh, Sanggun Roh, Hong-Gu Lee

Background

This study was performed to investigate the impact of exogenous ghrelin on the pancreatic α-amylase outputs and responses of pancreatic proteins to ghrelin that may relate to pancreatic exocrine.

Conclusions

Taken together, exogenous ghrelin by i.p. infusion plays a role in the pancreatic exocrine secretion via mitogen-activated protein kinase signaling pathway.

Methods

Sprague-Dawley male rats (9 weeks old, 300 ± 10 g) were injected with ghrelin via intraperitoneal (i.p.) infusion at dosage of 0, 0.1, 1.0 and 10.0 μg/kg body weight (BW), respectively. The plasma ghrelin and cholecystokinin (CCK) level were determined using enzyme immunoassay kit; the mRNA expression of ghrelin receptor (GHSR-1α) and growth hormone (GH) receptor were assessed by reverse transcription PCR; the expressions of pancreatic α-amylase activity, extracellular-signal-regulated kinases (ERK), phosphorylated extracellular-signal-regulated kinases (pERK) and c-Jun N-terminal kinase (JNK) were evaluated by western blotting; moreover the responses of pancreatic proteins to ghrelin were analyzed using the two-dimensional gel electrophoresis system.

Results

The exogenous ghrelin (1.0 and 10.0 μg/kg BW) elevated the level of plasma ghrelin (p < 0.05), and suppressed the expression of pancreatic α-amylase at a dose of 10.0 μg/kg BW (p < 0.05). No difference in the level of plasma CCK was observed, even though rats were exposed to any dose of exogenous ghrelin. In addition, a combination of western blot and proteomic analysis revealed exogenous ghrelin (10.0 μg/kg BW) induced increasing the JNK and ERK expressions (p < 0.05) and four proteins such as Destrin, Anionic trypsin-1, Trypsinogen, and especially eukaryotic translation initiation factor 3 in rat pancreas. Conclusions: Taken together, exogenous ghrelin by i.p. infusion plays a role in the pancreatic exocrine secretion via mitogen-activated protein kinase signaling pathway.

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