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.

Abstract

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.