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KMID : 0376219790160010043
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Chonnam Medical Journal
1979 Volume.16 No. 1 p.43 ~ p.54
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Hormonal and Enzymic Studies on Diabetes Mellitus Induced by Rodenticide N-3-Pyridylmethyl-N´-p-nitrophenylurea(RH-787)
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Abstract
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Since 1976, when Lee first reported RH-787-induced diabetes mellitus, over 250 cases have been reported in Korea and about 20 cases in America. To clarify its pathogenesis, immunoreactive insulin and C-peptide responses to oral glucose tolerance test were studied in 7 acute RH-787-poisoned patients, 5 maturity-on set diabetics and normal controls. Glucose intolerance with delayed but higher levels of insulin and C-peptide at 120 and 180 minutes were observed in the RH-787 group. The assay of portal plasma insulin in rats 2 hours after RH-787 ingestion showed that the insulin response to oral glucose load was higher than normal while marked glucose intolerance developed.
Glucose consumption and lactate productions from both glucose and inosine by rabbit erythrocytes were depressed to 55%, 60% and 80% of the controls, respectively, by 0. 1 mM RH-787 added in vitro. The inhibitory effect of RH-787 on the red cell glycolysis was apparent even at the concentration of 10-5 M and reached maximum at 10-3 M. In contrast, the production of 2, 3-diphosphoglycerate from inosine by red blood cells was not affected by RH-787.
RH-787 (10-3M) significantly depressed the hexokinase activity in normal human erythrocytes, while phosphofructokinase, phosphoglycerate kinase, pyruvate kinase and glucose-6-phosphate dehydrogenase activities were not altered. However, the hexokinase activity of red blood cells from 8 chronic RH-787 patients with 3 to 6 months´ treatment did not differ from 8 normal controls.
These results suggest that RH-787-induced diabetes mellitus may primarily have extrapancreatic factor (s) such as derangement of glucose metabolism at peripheral tissues rather than insulin secretory failure.
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