Effects of Kampo medicine, keishi-ka shakuyaku-to (TJ-60) on alteration of diacylglycerol metabolism in gastrointestinal smooth muscle of diabetic rats.
OBJECTIVE
To examine the effects of Kampo medicine, keishi-ka-shakuyaku-to (TJ-60) on the signal transduction in diabetic gastrointestinal dysfunction.


METHODS
Experimental diabetic models were prepared using streptozotocin (STZ)-treated Wistar rats. Randomly selected STZ rats were treated with insulin (12 U/kg/d) or TJ-60 (1% of food intake). Diacylglycerol (DG) and DG kinase activities were quantified in isolated aortic smooth muscle tissue.


RESULTS
One of the key element of the PI-turnover, DG kinase activity in resting state in gastric smooth muscle was significantly increased compared to the control value, and carbachol (CCh)-induced response was not detectable, but it was detected in the control rats. On the other hand resting activity in ileum did not differ from the control, but the CCh-induced responses were suppressed. Treatment with TJ-60 indicated resistant effects for the alteration of DG kinase activities in diabetic intestinal tissues. In order to reveal the mechanism of the effects, total content of DG was measured, because the DG plays important role in the PI-turnover and the DG converted from not only PI but also incorporated glucose under high glucose condition. Patterns of the change in DG levels were similar to those in DG kinase. These results indicate that the effect of TJ-60 occurs at the cellular level of DG.


CONCLUSIONS
Dysfunction of gastrointestinal smooth muscle in diabetes is mediated by an alternation of DG and DG kinase. TJ-60 influences the alteration and relief the dysfunction.
Nobe
Koji
K
Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku Tokyo, 142-8555 Japan.
Momose
Kazutaka
K
Sakai
Yasushi
Y
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D019852:Diacylglycerol Kinase / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D007082:Ileum / Q000473:pathology; D008297:Male; D020835:Medicine, Kampo; D009130:Muscle, Smooth / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000473:pathology
D004075:Diglycerides; D004365:Drugs, Chinese Herbal; C117960:gui-zhi-jia-shao-yao-tang; D019852:Diacylglycerol Kinase