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Signaling pathways underlying changes in the contractility of the stomach fundus smooth muscle in diabetic rats

Dong Min Kim1, Tin Myo Khing1, Wynn Thein1

  • 1Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.

Archives of Pharmacal Research
|July 2, 2020
PubMed

Insights

Diabetes mellitus (DM) impairs gastrointestinal (GI) fundus smooth muscle contractility by reducing key signaling pathway activity, including phospholipase C (PLC) and myosin light chain kinase (MLCK). This reveals a mechanism for DM-related GI dysfunction.

Area of Science:

  • Gastroenterology
  • Endocrinology
  • Physiology

Background:

  • Gastrointestinal (GI) motility dysfunction is a frequent complication in diabetes mellitus (DM).
  • Mechanisms underlying altered fundus smooth muscle contraction in DM are not fully understood.
  • This study investigates signaling pathways affecting fundus contraction in a rat model of DM.

Purpose of the Study:

  • To elucidate the signaling pathways involved in the reduced fundus smooth muscle contractility observed in diabetes mellitus.
  • To compare the activity of key enzymes and signaling molecules in fundus smooth muscle from control and diabetic rats.

Main Methods:

  • Diabetes mellitus was induced in Sprague-Dawley rats using streptozotocin.
  • Fundus smooth muscle contractility was assessed via electrical field stimulation and acetylcholine.
  • The involvement of specific signaling pathways was investigated using various inhibitors, including those for phospholipase C (PLC), protein kinase C (PKC), and myosin light chain kinase (MLCK).

Main Results:

  • Fundus smooth muscle contractility was significantly lower in diabetic rats compared to controls.
  • Activities of PLC, PKC, and MLCK were decreased in the DM group.
  • Reduced activity of these signaling molecules correlated with diminished fundus smooth muscle contractility in DM.

Conclusions:

  • Diabetes mellitus significantly impairs fundus smooth muscle contractility.
  • The reduction in contractility is mediated by decreased activity in the PLC, PKC, and MLCK signaling pathways.
  • These findings provide insight into the mechanisms of DM-associated GI motility disorders.
Keywords:
Diabetes mellitusFundusMLCKPLCSmooth muscle

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