title: Effect of endogenous insulin-like growth factor and stem cell factor on diabetic colonic dysmotility.
abstract: OBJECTIVE
  To investigate whether the reduction of stem cell factor (SCF) is mediated by decreased endogenous insulin-like growth factor (IGF)-1 in diabetic rat colon smooth muscle.
  
  
  METHODS
  Sixteen Sprague-Dawley rats were randomly divided into two groups: control group and streptozotocin-induced diabetic group. After 8 wk of streptozotocin administration, colonic motility function and contractility of circular muscle strips were measured. The expression of endogenous IGF-1 and SCF was tested in colonic tissues. Colonic smooth muscle cells were cultured from normal adult rats. IGF-1 siRNA transfection was used to investigate whether SCF expression was affected by endogenous IGF-1 expression in smooth muscle cells, and IGF-1 induced SCF expression effects were studied. The effect of high glucose on the expression of endogenous IGF-1 and SCF was also investigated.
  
  
  RESULTS
  Diabetic rats showed prolonged colonic transit time (252 ± 16 min vs 168 ± 9 min, P < 0.01) and weakness of circular muscle contraction (0.81 ± 0.09 g vs 2.48 ± 0.23 g, P < 0.01) compared with the control group. Endogenous IGF-1 and SCF protein expression was significantly reduced in the diabetic colonic muscle tissues. IGF-1 and SCF mRNA expression also showed a paralleled reduction in diabetic rats. In the IGF-1 siRNA transfected smooth muscle cells, SCF mRNA and protein expression was significantly decreased. IGF-1 could induce SCF expression in a concentration and time-dependent manner, mainly through the extracellular-signal-regulated kinase 1/2 signal pathway. High glucose inhibited endogenous IGF-1 and SCF expression and the addition of IGF-1 to the medium reversed the SCF expression.
  
  
  CONCLUSIONS
  Myopathy may resolve in colonic motility dysfunction in diabetic rats. Deficiency of endogenous IGF-1 in colonic smooth muscle cells leads to reduction of SCF expression.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Xu
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Tang
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Yang
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Yuan
authors.forename: Yue-Ji
authors.initials: YJ
authors.lastname: Ning
authors.forename: Yin-Juan
authors.initials: YJ
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation; D005772:Gastrointestinal Transit; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D001786:Blood Glucose; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019089:Stem Cell Factor; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Diabetes; Gastrointestinal motility function; Insulin-like growth factor-1; Smooth muscle cell; Stem cell factor