title: Blockade of p38 mitogen-activated protein kinase pathway ameliorates delayed gastric emptying in streptozotocin-induced diabetic rats.
abstract: OBJECTIVE
  Gastrointestinal dysfunction is one of the major complications of diabetes. The roles of inflammation in diabetes and its associated complications are increasingly recognized. p38 mitogen-activated protein kinase (MAPK) has been shown to be involved in the production of pro-inflammatory mediators. The aims of this study were to investigate the effects of SB203580, a specific p38 MAPK inhibitor, on delayed gastric emptying in diabetic rats and to elucidate its possible mechanism.
  
  
  METHODS
  SB203580 was administered in diabetic rats induced by intraperitoneal injection of streptozotocin. The gastric emptying rate of rats was measured by using phenol red solution, and blood glucose levels and body weights were observed. p38 MAPK activity and iNOS expression were assessed by Western blot analysis. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Gastric emptying was delayed significantly in diabetic rats and improved significantly with SB203580; high glucose significantly activated p38 MAPK and increased the expression of iNOS, TNF-α and IL-1β. The administration of SB203580 led to a significant decrease in the activation of p38 MAPK and the expression of iNOS, TNF-α and IL-1β.
  
  
  CONCLUSIONS
  Inflammation was associated with the development of delayed gastric emptying, and blockade of p38 MAPK pathway with SB203580 ameliorates delayed gastric emptying in diabetic rats, at least in part, by inhibiting the expression of iNOS, TNF-a and IL-1β. Therefore, p38MAPK may serve as a novel target for the therapy of diabetes-related gastrointestinal dysmotility.
authors.affiliation: Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Bo Yun
authors.initials: BY
authors.lastname: Qiu
authors.affiliation: Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Ying Xue
authors.initials: YX
authors.lastname: Yang
authors.affiliation: Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yu Pei
authors.initials: YP
authors.lastname: Zou
authors.affiliation: Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Hua Tian
authors.initials: HT
authors.lastname: Gan
authors.affiliation: Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: xiaoxiao334@hotmail.com.
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Huang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005746:Gastric Emptying / Q000187:drug effects* / Q000276:immunology; D018589:Gastroparesis / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000276:immunology; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007093:Imidazoles; D053583:Interleukin-1beta; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C093642:SB 203580
keywords: Delayed gastric emptying (diabetic gastroparesis); Inflammation; Pro-inflammatory mediators; p38 mitogen-activated protein kinase (MAPK)