糖尿病治療剤Phenethyldiguanideの作用機序に関する研究
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I studied the mechanism of Phenethyldiguanide (PEDG) with the following results : <BR>1) PEDG showed the hypoglycemic effect in the normal rat, alloxan rat and adrenalectomized rat. PEDG also showed the inhibition of hyperglycemia after glucose loading in the alloxan rat.<BR>2) The glycogen content in the liver of normal rat on fasting and glucose loading was less in the PEDG group than in the control group. The decrease of glycogen in the liver, as mentioned above, was restored slightly with pantothenic acid.<BR>3) PEDG enhanced the glucose uptake of diaphragm in the normal rat.<BR>4) In the normal rat PEDG inhibited acetylation, which was restored with pantothenic acid and Vitamin B<SUB>6</SUB>, but not with Vitamin B1. Also the decrease of CoA in the liver was noted on this occasion.<BR>5) PEDG had no effect on the activity of hexokinase and glucose-6-phosphatase in the liver homogenate of the normal rat.<BR>6) PEDG inhibited the activity of various enzymes which are related to TCA cycle.<BR>7) PEDG inhibited oxydative phosphorylation in the mitochondria of liver in the normal rat. The inhibition of oxygen consumption was also noted, but this inhibition was restored slightly with the excess addition of ATP or cytochrome C.<BR>8) PEDG had no effect on ATPase and d-amino acid oxydase in the liver of the normal rat.<BR>9) In diabetic patients, PEDG had no effects on the basal metabolic rate and urinary 17-Keto-steroids. Serum cholesterol decreased slightly. No definite changes were found in plasma non-esterified fatty acid 6 hours after the oral administration of PEDG.
- 日本内分泌学会の論文
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