Gastric motor effects of ghrelin and growth hormone releasing peptide 6 in diabetic mice with gastroparesis.
OBJECTIVE
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 microg/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 microg/kg) was also investigated. The effects of ghrelin or GHRP-6 (0.01-10 micromol/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 microg/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 fundic strips taken from diabetic mice. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.


CONCLUSIONS
Ghrelin and GHRP-6 increase gastric emptying in diabetic mice with gastroparesis, perhaps by activating peripheral cholinergic pathways in the enteric nervous system.
Qiu
Wen-Cai
WC
Department of General Surgery, The Affiliated Sixth Hospital of Medical School, Shanghai Jiaotong University, Shanghai 200233, China.
Wang
Zhi-Gang
ZG
Wang
Wei-Gang
WG
Yan
Jun
J
Zheng
Qi
Q
D000496:Alloxan; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000187:drug effects* / Q000503:physiopathology; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D018589:Gastroparesis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D054439:Ghrelin / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D013270:Stomach / Q000294:innervation / Q000503:physiopathology
D018678:Cholinergic Agents; D054439:Ghrelin; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D000496:Alloxan; D002217:Carbachol