As to the abnormalities of carbohydrate metabolism in diabetes mellitus, manifest depression in Embden-Myerhof cycle and Warburg Dickens pathway was pointed out. In addition, an attention was retently drawn to the hyperactivity of glucuronic acid (G. A.) pathway in diabetes mellitus, especially in relation to abnormalities of mucopolysaccharide metabolism.
In order to make the above remarks clear, several metabolic factors: in G. A. pathway were studied in alloxan diabetic (A. D.) rats.
Determinations of uridine diphosphoglucose dehy-drogenase (UDPG-DH) activity, glucuronyl transferase (Trf.) activity, and of uridine diphosphate glucuronic acid (UDPGA) level in the liver were performed as the factors related to the glucuronidation. And determinations of β-Glucuronidase (β-Gase) activities both in the liver and serum, and of glucuronolactone dehydrogenase (GAL-DH) activity in the liver were also carried out as the factors related to hydrolysis of glucuronides.
The results obtained were as follows;
1) Mean value of fasting blood sugar level was 131±12 mg/dl in control rats, and 483±43 mg/dl in A. D. rats, showing a significant elevation comparing to the control. Urine sugar level in A. D. rats ranged from 0.1g/dl to 0.25 g/dl.
2) A significant depression in UDPG-DH was observed in A. D. rats.
3) UDPGA level was slightly elevated in A. D. rats compared with the control, however no significant difference was observed between the two groups.
4) Trf. activity was slightly depressed also without significant difference.
5)β-Gase activities both in the liver and serum were significantly increased in A. D. rats.
The increase was, however, scarcely related to the other factors of G. A. pathway. The increase of the enzyme may be caused by the elevation of its production.
6) No significant change was observed in GAL. DH activities between control and A. D. rats.
In short, it was concluded that the metabolism in G. A. pathway was not elevated, but rather depressed in the diabetic state.

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For the purpose of elucidating the pathogenesis of human diabetic glomerulosclerosis (DGS), glomerular structures were examined by light and electron microscopy in eighteen alloxan-diabetic rats and eleven age-matched controls. According to the duration of diabetes, these diabetic rats were divided into four groups; group 0 with less than three months' duration, group I with three months, group II with six months and group III with nine months.
Following results were obtained:
1) The main alterations in the glomeruli of diabetic rats were thickening of the capillary basement membrane and increase in the mesangial matrix, both of which were evident after three months of diabetes.
2) In group I, II and II, the measurements of capillary basement membrane width revealed that the thickening of basement membrane was statistically significant as compared with controls and that the mean width increased with the lapse of disease apart from aging process.
3) Furthermore, the grading of increase in mesangial matrix demonstrated that it had tendency to augment with the duration of diabetes.
4) In addition to these changes, thickening of the basement membrane was found in Bowman's capsules and renal tubules in some diabetic cases, and also the cytoplasm of epithelium as well as mesangial cells contained prominent cell organelles and inclusions.
5) Although no arteriolar sclerosis nor typical nodular lesions were recognized in the present experiment, the glomerular lesion was very similar to that of the diffuse type in human DGS.
From this experiment it is inferred that the main alterations in the glomeruli of diabetic rats results from the metabolic abnormality consequent upon insulin deficiency and that at least one of the primary causes of human DGS is also such mechanism

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