A traditional herbal medicine, rikkunshi-to (TJ-43), prevents intracellular signaling disorders in gastric smooth muscle of diabetic rats.
Prevention of diabetic gastrointestinal dysfunction is of utmost importance. The present study demonstrated that diacylglycerol kinase (DGK) activity in diabetic gastric smooth muscle in the resting state was approximately 3.5-fold greater than that in controls. However, oral administration of TJ-43 (1% of food intake) or subcutaneous insulin injection (12 units/kg/day) in streptozotocin-induced diabetic rats (DM) for 2 weeks prevented DGK abnormalities based on the control level. Increased DGK activity in the resting state of DM was inhibited significantly by R59022, neomycin or staurosporine; in contrast, these drugs did not affect DGK activity in controls, insulin-treated DM or TJ-43-treated DM. In controls, the endogenous phosphatidic acid (PA) level was inhibited significantly by R59022 or neomycin but not affected by staurosporine. On the other hand, these three drugs significantly inhibited endogenous PA levels in DM, and neomycin significantly inhibited endogenous PA levels in insulin-treated and TJ-43-treated DM. This suggests that TJ-43 could prevent alteration of DGK activity and PA formation without reduction of blood glucose levels. Moreover, these effects were greater than those of insulin treatment. Results suggested that TJ-43 treatment influenced the hyperreactivity of DGK and DAG formation via phospholipase C activity. In conclusion, TJ-43 can be recommended with respect to enhancement of the quality of life in patients displaying diabetic gastrointestinal complications.
Division of Physiology, Department of Occupational Therapy, School of Nursing and Rehabilitation Sciences, Showa University, Yokohama 226, Japan. ysakai@nr.showa-u.ac.jp
Yasushi
Y
Sakai
Koji
K
Nobe
Yoshiaki
Y
Maruyama
Kazutaka
K
Momose
Ikuo
I
Homma
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D048909:Diabetes Complications; D019852:Diacylglycerol Kinase / Q000187:drug effects* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013270:Stomach / Q000502:physiology*; D013311:Streptozocin / Q000008:administration & dosage
D000903:Antibiotics, Antineoplastic; D004365:Drugs, Chinese Herbal; C084136:liu-jun-zi-tang; D013311:Streptozocin; D019852:Diacylglycerol Kinase