Brief Article
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World J Gastroenterol. Jun 7, 2013; 19(21): 3324-3331
Published online Jun 7, 2013. doi: 10.3748/wjg.v19.i21.3324
Effect of endogenous insulin-like growth factor and stem cell factor on diabetic colonic dysmotility
Yun Wang, Xin-Yu Xu, Yu-Rong Tang, Wei-Wei Yang, Yu-Feng Yuan, Yue-Ji Ning, Yin-Juan Yu, Lin Lin
Yun Wang, Xin-Yu Xu, Yu-Rong Tang, Wei-Wei Yang, Yu-Feng Yuan, Yue-Ji Ning, Yin-Juan Yu, Lin Lin, Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Author contributions: Wang Y and Xu XY contributed equally to this study; Wang Y, Xu XY, Ning YJ and Lin L designed research; Wang Y, Xu XY, Tang YR, Yang WW, Yuan YF, Ning YJ, and Yu YJ performed research; Wang Y, Yuan YF and Ning YJ analyzed data; and Wang Y and Lin L wrote the paper.
Supported by The National Natural Science Foundation of China, No. 30971354; The International Cooperation Project of Jiangsu Province Department of Health, No. SBZ201100103; The Graduate Innovation Foundation of Jiangsu Province, China, No. CXZZ11_0704
Correspondence to: Lin Lin, MD, PhD, Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Rd, Gulou District, Nanjing 210029, Jiangsu Province, China. lin9100@yahoo.com.cn
Telephone: +86-25-68136920 Fax: +86-25-83674636
Received: January 30, 2013
Revised: March 23, 2013
Accepted: April 18, 2013
Published online: June 7, 2013
Processing time: 124 Days and 21.5 Hours
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Diabetes; Gastrointestinal motility function; Insulin-like growth factor-1; Stem cell factor; Smooth muscle cell

Core tip: Endogenous insulin-like growth factor (IGF)-1 levels in diabetic rat colonic tissues were decreased. Hyperglycemia may be involved in initiating this change. In colonic smooth muscle cells, IGF-1 had a direct effect on increasing stem cell factor mRNA and protein levels mediated by extracellular-signal-regulated kinase 1/2 signaling.