摘要
AIM:To investigate the potential therapeutic significance of ghrelin and growth hormone releasing peptide 6 (GHRP-6) in diabetic mice with gastric motility disorders. METHODS: A diabetic mouse model was established by intraperitoneal (ip) injection of alloxan. Diabetic mice were injected ip with ghrelin or GHRP-6 (20-200 μg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) or D-Lys3-GHRP-6 (a growth hormone secretagogue receptor (GHS-R) antagonist) on the gastroprokinetic effect of ghrelin or GHRP-6 (100 μg/kg) was also investigated. The effects of ghrelin or GHRP-6 (0.01-10 μmol/L) on spontaneous or carbachol-induced contractile amplitude were also investigated in vitro, in gastric fundic circular strips taken from diabetic mice. The presence of growth hormone secretagogue receptor 1a transcripts in the fundic strips of diabetic mice was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: We established a diabetic mouse model with delayed gastric emptying. Ghrelin and GHRP-6 accelerated gastric emptying in diabetic mice with gastroparesis. In the presence of atropine or L-NAME, which delayed gastric emptying, ghrelin and GHRP-6 (100 μg/kg) failed to accelerate gastric emptying. D-Lys3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundicstrips taken from diabetic mice. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations. CONCLUSION: Ghrelin and GHRP-6 increase gastric emptying in diabetic mice with gastroparesis, perhaps by activating peripheral cholinergic pathways in the enteric nervous system.
AIM：To investigate the potential therapeutic significance of ghrelin and growth hormone releasing peptide 6 （GHRP-6） in diabetic mice with gastric motility disorders.
METHODS： A diabetic mouse model was established by intraperitoneal （ip） injection of alloxan. Diabetic mice were injected ip with ghrelin or GHRP-6 （20-200 μg/kg）, and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine, N^G-nitro-L-arginine methyl ester hydrochloride （L-NAME） or D-Lys^3-GHRP-6 （a growth hormone secretagogue receptor （GHS-R） antagonist） on the gastroprokinetic effect of ghrelin or GHRP-6 （100 μg/kg） was also investigated. The effects of ghrelin or GHRP-6 （0.01-10 μmol/L） on spontaneous or carbachol-induced contractile amplitude were also investigated in vitro, in gastric fundic circular strips taken from diabetic mice. The presence of growth hormone secretagogue receptor 1a transcripts in the fundic strips of diabetic mice was detected by reverse transcriptase polymerase chain reaction （RT-PCR）.
RESULTS： We established a diabetic mouse model with delayed gastric emptying. Ghrelin and GHRP-6 accelerated gastric emptying in diabetic mice with gastroparesis. In the presence of atropine or L-NAME, which delayed gastric emptying, ghrelin and GHRP-6 （100 μg/kg） failed to accelerate gastric emptying. D-Lys^3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundicstrips taken from diabetic mice. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.
CONCLUSION： Ghrelin and GHRP-6 increase gastric emptying in diabetic mice with gastroparesis, perhaps by activating peripheral cholinergic pathways in the enteric nervous system.
基金
National Nature Science Foundation of China, No. 30400429
关键词
胃排空
生长激素释放肽6
生长激素促分泌素受体
糖尿病
Gastric emptying
Ghrelin
Growth hormone releasing peptide 6
Growth hormone secretagogue receptor
Diabetic mice
