Electroacupuncture Regularizes Gastric Contraction and Reduces Apoptosis of Interstitial Cells of Cajal in Diabetic Rats

Background/AimsGastric dysmotility is a frequent complication among patients with diabetes mellitus. Electroacupuncture (EA) has been empirically used to relieve gastrointestinal symptoms. The aims of this study were to investigate the effects of EA on gastric contraction and the mechanisms of interstitial cells of Cajal (ICC) involved.Materials and MethodsMale Sprague–Dawley rats were randomized into the normal control, diabetes (DM), diabetic and sham EA (DM + SEA), diabetic and low-frequency EA (DM + LEA), and diabetic and high-frequency EA (DM + HEA) groups. Diabetic models were established and then treated with EA for 8 weeks. Body weight and blood glucose were recorded every 2 weeks. The spontaneous contractions of distal gastric strips were analyzed. Immunostaining and RT-PCR were used to test the apoptotic ICC, IGF-1/IGF-1R, and Nrf2/HO-1 pathways.ResultsThe body weight in the DM + LEA and DM + HEA groups were increased compared with that of the DM group, though there was no effect on the blood glucose. The gastric contractions were obviously disordered in the DM group, but EA could regularize the contractions. The number of apoptotic ICC was dramatically increased in the DM group, but reduced with EA treatment. Meanwhile, the IGF-1/IGF-1R pathway was verified to be significantly altered in diabetic rats. The Nrf2/HO-1 pathway was not significantly increased in the DM group. EA with different frequencies efficiently improved the expression of IGF-1/IGF-1R signaling and activated the Nrf2/HO-1 pathway.ConclusionEA could improve gastric motility dysfunction and attenuate ICC apoptosis possibly through the regulation of IGF-1/IGF-1R and Nrf2/HO-1 pathways. EA may be a potential therapeutic method for diabetic gastric motility dysfunction.

Ghrelin Is an Essential Factor for Motilin-Induced Gastric Contraction in Suncus murinus

Motilin was discovered in the 1970s as the most important hormone for stimulating strong gastric contractions; however, the mechanisms by which motilin causes gastric contraction are not clearly understood. Here, we determined the coordinated action of motilin and ghrelin on gastric motility during fasted and postprandial contractions by using house musk shrew (Suncus murinus; order: Insectivora, suncus named as the laboratory strain). Motilin-induced gastric contractions at phases I and II of the migrating motor complex were inhibited by pretreatment with (d-Lys3)-GHRP-6 (6 mg/kg/h), a ghrelin receptor antagonist. Administration of the motilin receptor antagonist MA-2029 (0.1 mg/kg) and/or (d-Lys3)-GHRP-6 (0.6 mg/kg) at the peak of phase III abolished the spontaneous gastric phase III contractions in vivo. Motilin did not stimulate gastric contractions in the postprandial state. However, in the presence of a low dose of ghrelin, motilin evoked phase III–like gastric contractions even in the postprandial state, and postprandial gastric emptying was accelerated. In addition, pretreatment with (d-Lys3)-GHRP-6 blocked the motilin-induced gastric contraction in vitro and in vivo, and a γ-aminobutyric acid (GABA) antagonist reversed this block in gastric contraction. These results indicate that blockade of the GABAergic pathway by ghrelin is essential for motilin-induced gastric contraction.

Coordination of motilin and ghrelin regulates the migrating motor complex of gastrointestinal motility in Suncus murinus

Motilin and ghrelin are the gastrointestinal (GI) hormones released in a fasting state to stimulate the GI motility of the migrating motor complex (MMC). We focused on coordination of the ghrelin/motilin family in gastric contraction in vivo and in vitro using the house musk shrew ( Suncus murinus ), a ghrelin- and motilin-producing mammal. To measure the contractile activity of the stomach in vivo, we recorded GI contractions either in the free-moving conscious or anesthetized S. murinus and examined the effects of administration of motilin and/or ghrelin on spontaneous MMC in the fasting state. In the in vitro study, we also studied the coordinative effect of these hormones on the isolated stomach using an organ bath. In the fasting state, phase I, II, and III contractions were clearly recorded in the gastric body (as observed in humans and dogs). Intravenous infusion of ghrelin stimulated gastric contraction in the latter half of phase I and in the phase II in a dose-dependent manner. Continuous intravenous infusion of ghrelin antagonist (d-Lys3-GHRP6) significantly suppressed spontaneous phase II contractions and prolonged the time of occurrence of the peak of phase III contractions. However, intravenous infusion of motilin antagonist (MA-2029) did not inhibit phase II contractions but delayed the occurrence of phase III contractions of the MMC. In the in vitro study, even though a high dose of ghrelin did not stimulate contraction of stomach preparations, ghrelin administration (10−10-10−7 M) with pretreatment of a low dose of motilin (10−10 M) induced gastric contraction in a dose-dependent manner. Pretreatment with 10−8 M ghrelin enhanced motilin-stimulated gastric contractions by 10 times. The interrelation of these peptides was also demonstrated in the anesthetized S. murinus . The results suggest that ghrelin is important for the phase II contraction and that coordination of motilin and ghrelin are necessary to initiate phase III contraction of the MMC.