Natriuretic Peptide-Dependent cGMP Signal Pathway Potentiated the Relaxation of Gastric Smooth Muscle in Streptozotocin-Induced Diabetic Rats

Xu, Dongmei; Liu, Lan; Cai, Yujun; Li, Xianglan; Qiu, Zhang-Xun; Zheng, Jin; Xu, Wen‐Xie

doi:10.1007/s10620-009-0766-8

Cited by 10 publications

(7 citation statements)

References 31 publications

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“…The breeding conditions remained unchanged. At 7 days post-injection, tail vein blood was collected and the success of the model was determined based on a glucose concentration >350 mg/dL (12,13). The model rats were randomly divided into groups of 10, including a normal control (NC) group and diabetic model (DM) groups examined 2 weeks (DM2W), 4 weeks (DM4W) and 6 weeks (DM6W) later.…”

Section: Methodsmentioning

confidence: 99%

Significance of dynamic changes in gastric smooth muscle cell apoptosis, PI3K-AKT-mTOR and AMPK-mTOR signaling in a rat model of diabetic gastroparesis

Zhang

Jiang

Cai

et al. 2017

Molecular Medicine Reports

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The aim of the present study was to investigate the significance of cell apoptosis, the phosphoinositide-3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway, and the 5' adenosine monophosphate-activated protein kinase (AMPK)‑mTOR pathways in the process of diabetic gastroparesis. Changes in gastric smooth muscle cells of diabetic rats with induced gastroparesis were examined. The diabetic rat model was established by dividing animals into a normal control group and diabetic model groups examined at 2, 4 and 6 weeks. Diabetic gastroparesis was evaluated by examining the rates of gastric residual pigment, whereas flow cytometry was used to detect the apoptosis of gastric smooth muscle cells. The expression levels of PI3K and phosphorylated (p‑) AKT, AMPK, mTOR, tuberous sclerosis complex 2, p70 ribosomal S6 kinase, and eukaryotic translation initiation factor 4‑binding protein 1 were determined in gastric muscles using western blot analysis. Diabetic gastroparesis was confirmed in models at 6 weeks. The apoptosis of gastric smooth muscle cells gradually increased in all diabetic groups, and significant changes were observed in key proteins involved in PI3K‑AKT‑mTOR and AMPK‑mTOR signaling. The results indicated that apoptosis was important in the occurrence of diabetic gastroparesis, and the PI3K‑AKT‑mTOR and AMPK‑mTOR pathways were activated during the apoptotic processes, but were incapable of regulating apoptosis.

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Section: Methodsmentioning

confidence: 99%

Significance of dynamic changes in gastric smooth muscle cell apoptosis, PI3K-AKT-mTOR and AMPK-mTOR signaling in a rat model of diabetic gastroparesis

Zhang

Jiang

Cai

et al. 2017

Molecular Medicine Reports

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“…CNP has a much higher affinity for the specific natriuretic peptide receptor B (NPR‐B), which is mainly distributed in the muscular layer of the gastrointestinal tract to inhibit smooth muscle cell contraction. When activated by CNP, pGC region of NPR‐B catalyzes the synthesis of cGMP from the GTP, and then, increased cGMP revealed inhibitory effect on the gastric and colonic motility of mice . Up‐regulation of the NPs signaling may be the cause of delayed gastric emptying in diabetic mice, but it has not been confirmed in colonic smooth muscle of diabetic mice.…”

Section: Introductionmentioning

confidence: 98%

“…When activated by CNP, pGC region of NPR-B catalyzes the synthesis of cGMP from the GTP, and then, increased cGMP revealed inhibitory effect on the gastric and colonic motility of mice. 7,8 Up-regulation of the NPs signaling may be the cause of delayed gastric emptying in diabetic mice, 9 but it has not been confirmed in colonic smooth muscle of diabetic mice. We need to explore the changes in NPs signaling in the colon of diabetic mice, and further investigate whether they were regulated by the EA in the stomach and colon of diabetic mice.…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture promotes the gastrointestinal motility of diabetic mice by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling

Song

et al. 2019

Neurogastroenterology Motil

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Background Electroacupuncture (EA) can promote gastrointestinal (GI) motility of diabetic mice, but the mechanism is not clearly elucidated. Natriuretic peptides (NPs) were related to the diabetes‐induced gut dysfunction of mice, which may be associated with ICC (interstitial cells of cajal). Besides, EA could increase the ICC of diabetic mice. Our aim was to explore whether EA can promote the gut motility by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling in diabetic mice, and the relationship between NPs and ICC. Methods Wild C57BL/6 male mice were divided into five groups: control group, diabetic mellitus (DM group), diabetic mellitus plus sham EA group (SEA), diabetic mellitus plus low‐frequency EA group (LEA), and diabetic mellitus plus high‐frequency group (HEA). Gastrointestinal motility was assessed by gastric emptying and GI transit test. Immunofluorescence staining was applied to assess the expression level of CNP, NPR‐B, and c‐Kit. Western blot, PCR, and ELISA were used to detect the level of CNP, NPR‐B, PDE2A, PDE3A, c‐Kit, mSCF, and cGMP content. The correlativity between NPR‐B and mSCF was evaluated by Pearson's correlation and linear regression analyses. Key Results (a) EA could improve the GI dysfunction of diabetic mice. (b) CNP, NPR‐B, and cGMP contents were decreased, but the level of PDE3A, c‐Kit, and mSCF was increased in the EA groups. (c) There was a negative correlation between NPR‐B and mSCF among the groups. Conclusions and Inferences Electroacupuncture promotes the GI function by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling in diabetic mice; up‐regulated mSCF/c‐Kit signaling by EA may be mediated partially via down‐regulation of CNP/NPR‐B signaling.

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“…Nevertheless, ANP may also influence gut motor behavior through a direct action because of its inhibitory effects on smooth muscle contractility (21). Moreover, the stomach and colon also appear to contain the highest amount of ANP messenger RNA (41).…”

Section: Discussionmentioning

confidence: 99%

Aortocaval fistula delays gastric emptying of liquid test meal in awake rats

Silva

Palheta

Oliveira

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Silva MT, Palheta RC Jr, Oliveira FG, de Lima JB, AntunesRodrigues J, Oliveira RB, Magalhães PJ, Santos AA. Aortocaval fistula delays gastric emptying of liquid test meal in awake rats. Am J Physiol Heart Circ Physiol 304: H1397-H1405, 2013. First published March 15, 2013 doi:10.1152/ajpheart.00827.2012.-Arteriovenous anastomoses disrupt cardiovascular and renal homeostasis, eliciting hemodynamic adjustments, resetting the humoral pattern, and inducing cardiac hypertrophy. Because acute circulatory imbalance alters gut motor behavior, we studied the effects of arteriovenous fistula placement on the gastric emptying (GE) of a liquid meal in awake rats. After laparotomy, we created an aortocaval fistula (ACF) by aorta and cava wall puncture with a 21-, 23-, or 26-gauge needle. The ACF was not created in the control group, which underwent sham operation. After 12, 24, or 48 h, mean arterial pressure, heart rate, and central venous pressure were continuously recorded, and cardiac output was estimated by thermal dilution. The rats were then gavage fed a test meal (i.e., phenol red in glucose solution), and fractional dye retention was determined 10, 20, or 30 min later. The effect of prior bleeding on ACF-induced GE delay, the role of neuroautonomic pathways, and changes in plasma hormone levels (i.e., angiotensin II, arginine vasopressin, atrial natriuretic peptide, corticosterone, and oxytocin) were evaluated. When compared with the sham-operated group, ACF rats exhibited arterial hypotension, higher (P Ͻ 0.05) heart rate, central venous pressure, and cardiac output values and increased (P Ͻ 0.05) gastric dye retention, a phenomenon prevented by bilateral subdiaphragmatic vagotomy and hexamethonium treatment. Pirenzepine also impaired the occurrence of gastric delay in subjects with ACF. In addition to causing hyperkinetic circulation, ACF placement delayed the GE of liquid in awake rats, an effect that likely involves a parasympathetic pathway. arteriovenous fistula; gastrointestinal motility; hyperkinetic circulation; intestinal transit; natriuretic hormone HYPERKINETIC CIRCULATION IS a systemic condition that may originate from an arteriovenous (AV) fistula, either as a congenital malformation or acquired after invasive procedures (e.g., percutaneous renal biopsy), surgeries (e.g., nephrectomy), or trauma (e.g., stab or gunshot wounds) (11,24). Large AV fistulas are considered a simple and reliable model to elicit congestive heart failure (13). Laboratory animals with an aortocaval fistula (ACF) present hemodynamic and neurohumoral changes that resemble those seen in patients with heart failure, including cardiac hypertrophy (22). These animals have high levels of cardiac output (CO) and mean circulatory filling pressure, in addition to tachycardia, low resistance to blood flow in circulatory vessels, and decreased mean arterial pressure (MAP) (17).As a consequence of inducing such changes, the placement of an AV fistula activates complex neurohumoral mechanisms that may restore hemodynamic homeostasis. During ...

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Natriuretic Peptide-Dependent cGMP Signal Pathway Potentiated the Relaxation of Gastric Smooth Muscle in Streptozotocin-Induced Diabetic Rats

Cited by 10 publications

References 31 publications

Significance of dynamic changes in gastric smooth muscle cell apoptosis, PI3K-AKT-mTOR and AMPK-mTOR signaling in a rat model of diabetic gastroparesis

Significance of dynamic changes in gastric smooth muscle cell apoptosis, PI3K-AKT-mTOR and AMPK-mTOR signaling in a rat model of diabetic gastroparesis

Electroacupuncture promotes the gastrointestinal motility of diabetic mice by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling

Aortocaval fistula delays gastric emptying of liquid test meal in awake rats

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