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Effect of endogenous insulin-like growth factor and stem cell factor on diabetic colonic dysmotility
Yun Wang1, Xin-Yu Xu, Yu-Rong Tang
1Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
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.
Insights
Diabetic rats exhibit reduced colon motility due to lower insulin-like growth factor-1 (IGF-1), which decreases stem cell factor (SCF) expression in smooth muscle.
Area of Science:
- Gastroenterology
- Endocrinology
- Cell Biology
Background:
- Diabetes mellitus is associated with gastrointestinal dysmotility.
- Stem cell factor (SCF) plays a role in smooth muscle function.
- Insulin-like growth factor-1 (IGF-1) is crucial for cellular growth and repair.
Purpose of the Study:
- To determine if reduced SCF in diabetic rat colon smooth muscle is linked to decreased IGF-1.
- To investigate the regulatory role of IGF-1 on SCF expression in colon smooth muscle cells.
Main Methods:
- Streptozotocin-induced diabetes model in rats.
- Assessment of colonic motility and muscle contractility.
- Measurement of IGF-1 and SCF expression (mRNA and protein) in colonic tissues and cultured smooth muscle cells.
- IGF-1 siRNA transfection and high glucose treatment experiments.
Main Results:
- Diabetic rats showed impaired colonic transit and reduced muscle contractility.
- Both IGF-1 and SCF expression were significantly decreased in diabetic rat colons.
- IGF-1 deficiency in smooth muscle cells reduced SCF expression.
- IGF-1 stimulated SCF expression via the ERK1/2 pathway.
- High glucose reduced IGF-1 and SCF; IGF-1 addition rescued SCF expression.
Conclusions:
- Diabetic colon smooth muscle dysfunction may involve myopathy.
- Reduced endogenous IGF-1 in colon smooth muscle cells is a key factor in decreased SCF expression.
- This study elucidates a molecular mechanism linking diabetes, IGF-1 deficiency, and impaired colon motility.
