Impaired intracellular signal transduction in gastric smooth muscle of diabetic BB/W rats

Am J Physiol. 1996 Mar;270(3 Pt 1):G411-7. doi: 10.1152/ajpgi.1996.270.3.G411.


The pathophysiological mechanisms responsible for diabetic gastroparesis remain unclear. Diabetes mellitus occurs spontaneously in 90% of a partially inbred colony of BB/W rats. This animal model resembles human insulin-dependent diabetes and is suitable for investigating the mechanism of diabetic gastroparesis. Diabetic BB/W rats were killed 6 mo after the onset of diabetes. Muscle contraction experiments and [3H]acetylcholine release studies were performed with muscle strips of the gastric body. Biochemical measurements of inositol trisphosphate (IP3) and protein kinase C (PKC) in gastric muscle were performed to characterize abnormalities of the intracellular signal transduction system in gastric myocytes. Circular muscle contractions in response to direct myogenic stimulants, carbachol (10(-7) - 10 (-3)M) or substance P (10(-7) - 10(-5)M), were significantly impaired in diabetic BB/W rats compared with controls. Similarly, muscle contractions in response to NaF (10 mM), a direct stimulant of G proteins, were also impaired in diabetic BB/W rats. In contrast, muscle contractions in response to KCl (25-75 mM) were similar between control and diabetic BB/W rats, indicating normal voltage-dependent Ca2+ entry in muscle strips obtained from diabetics BB/W rats. [3H]acetylcholine release from gastric myenteric plexus in response to electrical transmural stimulation remained intact in diabetic BB/W rats. In separate studies, we demonstrated that carbachol (10(-6) - 10(-4)M) -induced IP3 responses were significantly reduced in diabetic rats compared with control. In addition, there was also impairment of translocation of PKC in diabetic BB/W rats. These observations indicate that myogenic impairment occurred in diabetic BB/W rats. This resulted from altered intracellular signal transduction involving abnormal IP3 production and PKC translocation.

Publication types

  • Comparative Study

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Calcium / metabolism
  • Carbachol / pharmacology
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cytosol / metabolism
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Electric Stimulation
  • Humans
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Inositol Phosphates / metabolism*
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Muscle, Smooth / physiopathology*
  • Potassium Chloride / pharmacology
  • Protein Kinase C / metabolism
  • Rats
  • Rats, Inbred BB
  • Reference Values
  • Signal Transduction*
  • Sodium Fluoride / pharmacology
  • Stomach / drug effects
  • Stomach / physiology
  • Stomach / physiopathology*
  • Substance P / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology


  • Inositol Phosphates
  • Substance P
  • Potassium Chloride
  • Inositol 1,4,5-Trisphosphate
  • Carbachol
  • Sodium Fluoride
  • Protein Kinase C
  • Acetylcholine
  • Tetradecanoylphorbol Acetate
  • Calcium