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Weng L, Chen TH, Zheng Q, Weng WH, Huang L, Lai D, Fu YS, Weng CF. Syringaldehyde promoting intestinal motility with suppressing α-amylase hinders starch digestion in diabetic mice. Biomed Pharmacother 2021; 141:111865. [PMID: 34246193 DOI: 10.1016/j.biopha.2021.111865] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 06/24/2021] [Accepted: 06/28/2021] [Indexed: 12/14/2022] Open
Abstract
The antihyperglycemic potential of syringaldehyde has been previously investigated; however, the underlying mechanism remains unclear. In this study, we performed a postprandial glucose test (in vivo) including oral glucose tolerance test (OGTT) and oral starch tolerance test (OSTT) in fructose-induced diabetic mice on a high-fat diet for mimicking type 2 diabetes to explore the hypoglycemic efficacy of syringaldehyde and the underlined molecular involvement of syringaldehyde in a glucose-lowering effect. The results revealed that syringaldehyde dose-dependently suppressed blood glucose in both the OSTT and OGTT when referenced to acarbose and metformin, respectively. Surprisingly, syringaldehyde triggered jejunum motility (ex vivo) via activation of the muscarinic-type acetylcholine receptor. By performing virtual screening with molecular docking, the data showed that syringaldehyde nicely interacted with glucagon-like peptide 1 receptor (GLP-1R), peroxisome proliferator-activated receptor (PPAR), dipeptidyl peptidase-IV (DPP-4), acetylcholine M2 receptor, and acetylcholinesterase. These results showed that syringaldehyde can potentiate intestinal contractility to abolish the α-amylase reaction when concurrently reducing retention time and glucose absorption to achieve a glucose-lowering effect in diabetic mice, suggesting its potential therapeutic benefits with improvement for use as a prophylactic and treatment.
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Affiliation(s)
- Lebin Weng
- Department of Physiology, School of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Ting-Hsu Chen
- Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan.
| | - Qingyan Zheng
- Department of Physiology, School of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Wei-Hao Weng
- Department of Pharmacy, China Medical University, Taichung 40402, Taiwan.
| | - Liyue Huang
- Department of Physiology, School of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Dong Lai
- Medical Research Center, the Second Affiliated Hospital of Xiamen Medical College, Xiamen 361021, Fujian, China.
| | - Yaw-Syan Fu
- Medical Research Center, the Second Affiliated Hospital of Xiamen Medical College, Xiamen 361021, Fujian, China; Department of Anatomy, School of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Ching-Feng Weng
- Department of Physiology, School of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China; Medical Research Center, the Second Affiliated Hospital of Xiamen Medical College, Xiamen 361021, Fujian, China.
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Smiley R, McCallum R, Showkat Ali M. Decreased Level of Neuropeptide Y Is Associated With Gastroparesis in Male Diabetic Rats. Gastroenterology Res 2021; 13:246-252. [PMID: 33447303 PMCID: PMC7781275 DOI: 10.14740/gr1322] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 10/21/2020] [Indexed: 11/13/2022] Open
Abstract
Background Substance P (SP) and neuropeptide Y (NPY), excitatory and inhibitory neuropeptides, respectively, may impact gastric motility in patients with diabetic mellitus (DM). We investigated these neuropeptide levels, NPY receptors, total nitric oxide synthase (NOS) levels, and neuronal NOS alpha (nNOSα) activation status and levels in streptozotocin-induced type I diabetes in male rats. Methods Rats were grouped based on serum glucose and gastric emptying time: normal untreated control (CM), diabetic (DM) and diabetic gastroparesis (DM + GP). Neuropeptide serum levels were determined by enzyme-linked immunosorbent assay (ELISA). Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting measured NPY receptors, Y1 and Y2, and nNOSα expression. Low-temperature SDS-PAGE followed by western blotting was used to measure the dimerization of nNOSα. An NOS colorimetric assay kit was used to measure total NOS activity. Results SP levels were significantly decreased (P < 0.05) in DM and DM + GP compared to CM. NPY levels were significantly decreased (P < 0.05) in DM compared to CM, and DM + GP had a more significantly decreased NPY when compared to both DM and CM. Protein levels of neuropeptide receptor Y1 (NPY-Y1) in the smooth muscle of pylorus were significantly increased in DM, but not in DM + GP when compared to CM. Neuropeptide receptor Y2 (NPY-Y2) was not detected. Changes in nNOSα activity and their protein levels, as well as total NOS activity, among the groups were insignificant. Conclusions Increased expression of pylorus NPY-1R and decreased serum NPY are present in diabetes. A more pronounced decreased serum NPY with no NPY-1R upregulation in pyloric smooth muscle is associated with gastroparesis. NPY levels show no relationship with nNOSα levels, their activation status, or total NOS activity in pyloric smooth muscle. These data suggest a pathophysiological role of severely depleted NPY and absence of NPY-Y1 upregulation for gastroparesis phenotype.
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Affiliation(s)
- Rebecca Smiley
- Department of Clinical Investigation, William Beaumont Army Medical Center, 5005 N. Piedras Street, El Paso, TX 79920-5001, USA
| | - Richard McCallum
- Department of Internal Medicine, Texas Tech Health Science Center, Paul L. Foster School of Medicine, 4800 Alberta Ave., El Paso, TX 79905-2709, USA
| | - Mohammed Showkat Ali
- Department of Clinical Investigation, William Beaumont Army Medical Center, 5005 N. Piedras Street, El Paso, TX 79920-5001, USA
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Sandoval-Skeet N, Kaufman JA, Castro MJ, Al-Nakkash L. Genistein diet does not modify crypt morphology in the ob/ob mouse jejunum: a comparison of cryostat and clearing techniques. Diabetes Metab Syndr Obes 2018; 11:863-873. [PMID: 30568474 PMCID: PMC6276911 DOI: 10.2147/dmso.s182501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Diabetes is commonly associated with gastrointestinal dysfunction. We have previously shown that transepithelial short circuit current, Isc (chloride secretion), is significantly reduced in the jejunum from ob/ob mice vs lean controls, and consumption of 600 mg genistein/kg of diet (600 G) for 4 weeks significantly rescues Isc. We aimed to evaluate whether morphological changes in the jejunal crypts contribute to the rescue of Isc. METHODS Male mice (ob/ob and lean controls) were fed either a genistein-free diet or genistein-containing diet (600 G). Comparisons of crypt morphology were made for crypt depth, length, and numbers of proliferative cells. Assessments of crypt measures using DAPI and 5-ethynyl-2'-deoxyuridine (EdU) were performed using traditional cryostat sectioning and an innovative 3D optical clearing method. RESULTS We found that crypt length in the ob/ob genistein-fed group was significantly greater when measured with cleared tissue (85.19±4.73 µm, P<0.05, n=8) compared to lengths measured with cryostat (65.42±3.48 µm, n=8). In addition, proliferative EdU+ counts were approximately fivefold greater with clearing, compared to counts obtained via single plane images from cryostat sections for all groups measured. The average length to EdU+ ratio was unchanged between groups. CONCLUSION Thus, we conclude that genistein diet does not affect overall cellular proliferation or crypt morphology, other than for the modest increased crypt length measured via clearing in the ob/ob genistein group. The increase in crypt length is likely indicative of the greater accuracy of the 3D measures compared to single plane. Genistein diet-induced increases in the intestinal Isc are therefore likely not attributed to changes in intestinal crypt morphology.
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Affiliation(s)
| | | | | | - Layla Al-Nakkash
- Department of Physiology, Midwestern University, Glendale, AZ 85308, USA,
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Zhao J, Yang J, Liao D, Gregersen H. Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine. Clin Exp Gastroenterol 2017; 10:303-314. [PMID: 29238211 PMCID: PMC5716675 DOI: 10.2147/ceg.s145016] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Background Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. Objective We aimed to characterize the stimulus–response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Design Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress–strain, spike rate increase ratio (SRIR), and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Results Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity (P<0.05). The stress relaxed less in the diabetic intestinal segment (P<0.05). Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Conclusion Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients.
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Affiliation(s)
- Jingbo Zhao
- Giome Academia, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Jian Yang
- Giome Academia, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Donghua Liao
- Giome Academia, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Hans Gregersen
- Giome Center, Department of Surgery, Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, Hong Kong
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Zhao M, Liao D, Zhao J. Diabetes-induced mechanophysiological changes in the small intestine and colon. World J Diabetes 2017; 8:249-269. [PMID: 28694926 PMCID: PMC5483424 DOI: 10.4239/wjd.v8.i6.249] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 04/05/2017] [Accepted: 05/05/2017] [Indexed: 02/05/2023] Open
Abstract
The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients.
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Schacht S, Masood F, Catmull S, Dolan R, Altabtabaee R, Grow W, Al-Nakkash L. Dietary Genistein Influences Number of Acetylcholine Receptors in Female Diabetic Jejunum. J Diabetes Res 2017; 2017:3568146. [PMID: 28835900 PMCID: PMC5556993 DOI: 10.1155/2017/3568146] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2017] [Accepted: 07/17/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Intestinal dysfunction in the ob/ob mouse model of diabetes mimics that seen clinically. METHODS We determined the effects of a 4-week genistein diet (600 mg genistein/kg food) on intestinal function (contractility, morphology, AChR, and motility) in female ob/ob and lean mice. RESULTS Contractility of the jejunum in response to incrementally increasing concentrations of KCl was comparable in ob/ob females and lean controls regardless of a genistein-diet. There were no changes in the wall thickness measured. We assessed the number of clusters of AChR in the jejunum wall; AChR were decreased by 48% in ob/ob mice versus leans, and the genistein diet reversed this. In utilizing a video-imaging system to evaluate gastrointestinal motility, we determined that the distance between consecutive contractile events was significantly increased by 1.87-fold in ob/ob mice versus leans, and the genistein diet was without effect. CONCLUSIONS These data suggest that slowed intestinal transit in the diabetic ob/ob mouse may be due in part to decreased AChR and decreased contraction events occurring per unit time. A genistein diet rescues the number of AChR to levels of leans yet did not change the number of contractile events. Feeding ob/ob mice a genistein-rich diet has potential therapeutic benefits towards improving the debilitating diabetes-related gastrointestinal dysfunction.
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Affiliation(s)
- Sydney Schacht
- Department of Physiology, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA
| | - Faisal Masood
- Department of Physiology, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA
| | - Shawn Catmull
- Department of Physiology, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA
| | - Robert Dolan
- Department of Physiology, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA
| | - RussL Altabtabaee
- Department of Physiology, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA
| | - Wade Grow
- Department of Anatomy, Arizona College of Osteopathic Medicine, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA
| | - Layla Al-Nakkash
- Department of Physiology, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA
- *Layla Al-Nakkash:
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Zhao J, Chen P, Gregersen H. Stress-strain analysis of contractility in the ileum in response to flow and ramp distension in streptozotocin-induced diabetic rats--association with advanced glycation end product formation. J Biomech 2015; 48:1075-83. [PMID: 25682538 DOI: 10.1016/j.jbiomech.2015.01.027] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Revised: 12/23/2014] [Accepted: 01/24/2015] [Indexed: 12/28/2022]
Abstract
This study compared the ileal contractility and analyzed the association between contractility with advanced glycation end product (AGE) formation in normal and streptozotocin (STZ)-induced diabetic rats. Nine STZ-induced diabetic rats (Diabetes group) and 9 normal rats (Normal group) were used. The motility experiments were carried out on ileums in organ baths containing physiological Krebs solution. Ileal pressure and diameter changes were obtained from basic, flow-induced and ramp distension-induced contractions. The frequency and amplitude of contractions were analyzed from pressure-diameter curves. Distension-induced contraction thresholds and maximum contraction amplitude of basic and flow-induced contractions were calculated in terms of stress and strain. AGE and its receptor (RAGE) in the layers were detected by immunohistochemistry staining. The maximum stress of flow-induced contractions was lowest in the Diabetes Group (P<0.05). During ramp distension, the pressure and stress thresholds and Young's modulus to induce phasic contraction were lowest in the Diabetes Group (P<0.05 and P<0.01). AGE and RAGE expressions in the different ileum layers were highest in the Diabetes group. The contraction pressure and stress thresholds were significantly associated with AGE expression in the muscle layer and RAGE expression in mucosa epithelium and neurons. The diabetic intestine was hypersensitive to distension for contraction induction. However, the contraction force produced by smooth muscle was lowest in diabetic rats. Increased AGE/RAGE expression was associated with the contractility changes in diabetic rats.
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Affiliation(s)
- Jingbo Zhao
- Institute of Clinical medicine, Aarhus University, Brendstrupgaardsvej 100, Aarhus N 8200, Denmark; GIOME Center, College of Bioengineering, Chongqing University, Chongqing 400045, China
| | - Pengmin Chen
- Department of Molecular Biology, Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China
| | - Hans Gregersen
- GIOME Center, College of Bioengineering, Chongqing University, Chongqing 400045, China.
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Leung L, Kang J, Rayyan E, Bhakta A, Barrett B, Larsen D, Jelinek R, Willey J, Cochran S, Broderick TL, Al-Nakkash L. Decreased basal chloride secretion and altered cystic fibrosis transmembrane conductance regulatory protein, Villin, GLUT5 protein expression in jejunum from leptin-deficient mice. Diabetes Metab Syndr Obes 2014; 7:321-30. [PMID: 25092993 PMCID: PMC4112754 DOI: 10.2147/dmso.s63714] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Patients with diabetes and obesity are at increased risk of developing disturbances in intestinal function. In this study, we characterized jejunal function in the clinically relevant leptin-deficient ob/ob mouse, a model of diabetes and obesity. We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from 12-week-old ob/ob and lean C57BL/6J (female and male) mice. The basal Isc was significantly decreased (~30%) in the ob/ob mice (66.5±5.7 μA/cm(2) [n=20]) (P< 0.05) compared with their lean counterparts (95.1±9.1 μA/cm(2) [n=19]). Inhibition with clotrimazole (100 μM, applied bilaterally) was significantly reduced in the ob/ob mice (-7.92%±3.67% [n=15]) (P<0.05) compared with the lean mice (10.44%±7.92% [n=15]), indicating a decreased contribution of Ca(2+)-activated K(+) (KCa) channels in the ob/ob mice. Inhibition with ouabain (100 μM, applied serosally) was significantly reduced in the ob/ob mice (1.40%±3.61%, n=13) (P< 0.05) versus the lean mice (18.93%±3.76% [n=18]), suggesting a potential defect in the Na(+)/K(+)-adenosine triphosphate (ATP)ase pump with leptin-deficiency. Expression of cystic fibrosis transmembrane conductance regulatory protein (CFTR) (normalized to glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) was significantly decreased ~twofold (P<0.05) in the ob/ob mice compared with the leans, whilst crypt depth was unchanged. Villi length was significantly increased by ~25% (P<0.05) in the ob/ob mice compared with the leans and was associated with an increase in Villin and GLUT5 expression. GLUT2 and SGLT-1 expression were both unchanged. Our data suggests that reduced basal jejunal Isc in ob/ob mice is likely a consequence of reduced CFTR expression and decreased activity of the basolateral KCa channel and Na(+)/K(+)-ATPase. Understanding intestinal dysfunctions in ob/ob jejunum may allow for the development of novel drug targets to treat obesity and diabetes.
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Affiliation(s)
- Lana Leung
- Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
| | - Jonathan Kang
- Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
| | - Esa Rayyan
- Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
| | - Ashesh Bhakta
- Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
| | - Brennan Barrett
- Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
| | - David Larsen
- Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
| | - Ryan Jelinek
- Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
| | - Justin Willey
- Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
| | - Scott Cochran
- Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
| | - Tom L Broderick
- Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
| | - Layla Al-Nakkash
- Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
- Correspondence: Layla Al-Nakkash, Department of Physiology, Midwestern University, 19555 N 59th Avenue, Glendale, AZ, 85308, USA, Tel +1 623 572 3719, Fax +1 623 572 3673, Email
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Zhao J, Chen P, Gregersen H. Stress-strain analysis of jejunal contractility in response to flow and ramp distension in type 2 diabetic GK rats: effect of carbachol stimulation. J Biomech 2013; 46:2469-76. [PMID: 23932327 DOI: 10.1016/j.jbiomech.2013.07.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2013] [Revised: 07/09/2013] [Accepted: 07/09/2013] [Indexed: 12/16/2022]
Abstract
Investigation of intestinal motility in a genetic model of GK rats abandons the possible neurotoxic effect of streptozotocin in streptozotocin-induced diabetic model. Seven GK male rats (GK group) and nine normal Wistar rats (Normal group) were used in the study. The motility experiments were carried out in an organ bath containing physiological Krebs solution. Before and after 10(-5)M carbachol application, the pressure and diameter changes of jejunum were obtained in relation to (1) basic contraction, (2) flow-induced contraction with different outlet resistance pressures and (3) contractions induced by ramp distension. The frequency and amplitude of contractions were analyzed from pressure-diameter curves. Distension-induced contraction thresholds and maximum contraction amplitude of basic and flow-induced contractions were calculated in terms of stress and strain. (1) The contraction amplitude increased to the peak value in less than 10s after adding carbachol. More than two peaks were observed in the GK group. (2) Carbachol decreased the pressure and stress threshold and Young's modulus in the GK group (P<0.01). (3) Carbachol increased the maximum pressure and stress of flow-induced contractions at most outlet pressure levels in both two groups (P<0.001). Furthermore, the flow-induced contractions were significantly bigger at low outlet pressure levels in GK group (P<0.05 and P<0.01). (4) The contraction frequency, the strain threshold and the maximum contraction strain did not differ between the two groups (P>0.05) and between before and after carbachol application (P>0.05). In GK diabetic rats, the jejunal contractility was hypersensitive to flow and distension stimulation after carbachol application.
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Affiliation(s)
- Jingbo Zhao
- Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, DK 9000 Aalborg, Denmark; Clinical Institute, Aarhus University, 8200 Aarhus N, Denmark; The College of Bioengineering, Chongqing University, Chongqing, China.
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Zhang WP, Jiang B, Huo MD, Ding SQ, Wu YY, Xu S, Huangfu SH. Effect of colonic bypass with ileorectal anastomosis on plasma levels of SP and VIP in rats with slow transit constipation. Shijie Huaren Xiaohua Zazhi 2012; 20:585-589. [DOI: 10.11569/wcjd.v20.i7.585] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the influence of colonic bypass with ileorectal anastomosis on plasma levels of substance P (SP) and vasoactive intestinal peptide (VIP) in rats with slow transit constipation (STC).
METHODS: A total of 72 rats were used in the study, of which 10 were included in normal control group, and 62 were used to induce STC by intragastric administration of gradually increasing doses of rhubarb suspension. STC was successfully induced in 57 rats, and 12 of them were used as model controls and killed before operation. The remaining 45 rats were randomized into operation group (n = 35) and recovery group (n = 10). Plasma levels of SP and VIP were measured in each group.
RESULTS: SP: Compared to the normal control group, plasma levels of SP decreased significantly in the model group (63.364 ± 4.211 vs 81.032 ± 4.237, P < 0.01). Plasma levels of SP were lower in the recovery group than in the model group (50.138 ± 5.283 vs 63.364 ± 4.211, P < 0.01), but were higher in the operation group than in the recovery group (58.165 ± 6.592 vs 50.138 ± 5.283, P < 0.05). Compared to the normal control group, plasma levels of VIP increased significantly in the model group (32.152 ± 6.204 vs 25.469 ± 4.523, P < 0.01). Plasma levels of VIP were lower in the recovery group than in the model group (25.217 ± 3.517 vs 32.152 ± 6.204, P < 0.05), but showed no significant difference between the normal control group and recovery group.
CONCLUSION: Colonic bypass with ileorectal anastomosis significantly improves symptoms and reduces the further deterioration of colonic function in STC rats.
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Zheng Q, Qiu WC, Yan J, Wang WG, Yu S, Wang ZG, Ai KX. Prokinetic effects of a ghrelin receptor agonist GHRP-6 in diabetic mice. World J Gastroenterol 2008; 14:4795-9. [PMID: 18720542 PMCID: PMC2739343 DOI: 10.3748/wjg.14.4795] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the effects of a ghrelin receptor agonist GHRP-6 on delayed gastrointestinal transit in alloxan-induced diabetic mice.
METHODS: A diabetic mouse model was established by intraperitoneal injection with alloxan. Mice were randomized into two main groups: normal mice and diabetic mice treated with GHRP-6 at doses of 0, 20, 50, 100 and 200 μg/kg ip. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) were studied in mice after they had a phenol red meal following injection of GHRP-6. Based on the most effective GHRP-6 dosage, atropine was given at 1 mg/kg for 15 min before the GHRP-6 injection for each measurement. The mice in each group were sacrificed 20 min later and the percentages of GE, IT, and CT were calculated.
RESULTS: Percentages of GE, IT, and CT were significantly decreased in diabetic mice as compared to control mice. In the diabetic mice, GHRP-6 improved both GE and IT, but not CT. The most effective dose of GHRP-6 was 200 μg/kg and atropine blocked the prokinetic effects of GHRP-6 on GE and IT.
CONCLUSION: GHRP-6 accelerates delayed GE and IT, but has no effect on CT in diabetic mice. GHRP-6 may exert its prokinetic effects via the cholinergic pathway in the enteric nervous system, and therefore, has therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.
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Qiu WC, Wang ZG, Lv R, Wang WG, Han XD, Yan J, Wang Y, Zheng Q, Ai KX. Ghrelin improves delayed gastrointestinal transit in alloxan-induced diabetic mice. World J Gastroenterol 2008; 14:2572-7. [PMID: 18442208 PMCID: PMC2708372 DOI: 10.3748/wjg.14.2572] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of ghrelin on delayed gastrointestinal transit in alloxan-induced diabetic mice.
METHODS: A diabetic mouse model was established by intraperitoneal injection with alloxan. Mice were randomized into two main groups: normal mice group and diabetic mice group treated with ghrelin at doses of 0, 20, 50, 100 and 200 &mgr;g/kg ip. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) were studied in mice after they had a phenol red meal following injection of ghrelin. Based on the most effective ghrelin dosage, atropine was given at 1 mg/kg 15 min before the ghrelin injection for each measurement. The mice in each group were sacrificed 20 min later and their stomachs, intestines, and colons were harvested immediately. The amount of phenol red was measured. Percentages of GE, IT, and CT were calculated.
RESULTS: Percentages of GE, IT, and CT were significantly decreased in diabetic mice as compared to control mice (22.9 ± 1.4 vs 28.1 ± 1.3, 33.5 ± 1.2 vs 43.2 ± 1.9, 29.5 ± 1.9 vs 36.3 ± 1.6, P < 0.05). In the diabetic mice, ghrelin improved both GE and IT, but not CT. The most effective dose of ghrelin was 100 &mgr;g/kg and atropine blocked the prokinetic effects of ghrelin on GE and IT.
CONCLUSION: Ghrelin accelerates delayed GE and IT but has no effect on CT in diabetic mice. Ghrelin may exert its prokinetic effects via the cholinergic pathway in the enteric nervous system, and therefore has therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.
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Li Y, Wang J, Li YP, Hu Y, Tang J, Yu LF. Effect of Qilang Decoction on substance P and vasoactive intestine polypeptide in the mucous enteric nervous system. Shijie Huaren Xiaohua Zazhi 2008; 16:272-276. [DOI: 10.11569/wcjd.v16.i3.272] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of Qilang Decoction on substance P (SP) and vasoactive intestine polypeptide (VIP) in mucous and muscular layers of colon and its possible mechanism.
METHODS: Fifty Kunming mice were divided into normal group (A), model group of constipated mice (B) and three different treatment groups (C, D, E). Positively stained SP and VIP were compared among the 5 groups using immunohistomisry and pathology analysis system.
RESULTS: Strongly positive SP [(9.35 ± 2.44) × 105, (7.69 ± 4.16) × 105] and VIP [(9.48 ± 4.54) × 105, (6.65 ± 3.30) × 105] were found in the mucous membrane and muscular layers of the normal colon group compared with the negative group (P < 0.05). The SP and VIP level was higher in the mucous membrane layer than in the muscular layer. The SP level [(5.25 ± 0.72) × 105, (5.61 ± 1.59) × 105, (5.61 ± 2.03) × 105 and (2.28 ± 0.82) × 105, (3.23 ± 0.80) × 105, (3.45 ± 0.88) × 105] and the VIP level [(4.19 ± 1.13) × 105, (7.27 ± 2.27) × 105, (3.40 ± 1.51) × 105 and (1.54 ± 0.39) × 105, (1.40 ± 1.30) × 105, (1.47 ± 0.57) × 105] decreased considerably in the mucous membrane and muscular layers of the Qilang Decoction groups compared with the normal group (P < 0.05).
CONCLUSION: Qilang Decoction may regulate the distribution of SP and VIP in the colon by directly stimulating the peristalsis of the colon, decreasing the response of SP to the nerve cluster of the colon mucous membrane, and releasing SP, thus leading to increased excretion of intestinal juice, which lubricates the intestines for easy bowel movements.
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Abstract
Gastrointestinal (GI) sensory-motor abnormalities are common in patients with diabetes mellitus and may involve any part of the GI tract. Abnormalities are frequently sub-clinical, and fortunately only rarely do severe and life-threatening problems occur. The pathogenesis of abnormal upper GI sensory-motor function in diabetes is incompletely understood and is most likely multi-factorial of origin. Diabetic autonomic neuropathy as well as acute suboptimal control of diabetes has been shown to impair GI motor and sensory function. Morphological and biomechanical remodeling of the GI wall develops during the duration of diabetes, and may contribute to motor and sensory dysfunction. In this review sensory and motility disorders of the upper GI tract in diabetes is discussed; and the morphological changes and biomechanical remodeling related to the sensory-motor dysfunction is also addressed.
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Affiliation(s)
- Jingbo Zhao
- Center of Excellence in Visceral Biomechanics and Pain, the Research Building room 404, Aalborg Hospital, Sdr. Skovvej 15, DK-9000 Aalborg, Denmark.
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