The effect of lipid metabolism, especially catabolism of triglyceride on carbohydrate metabolism, has been studied in rabbits. The results were as follows; 1) A high fat diet did not increase the fasting blood sugar but this level was significantly elevated by the addition of orally adminitered Δ' 17α-methyltestosterone. 2) The oral administration of lipid or Δ' 17α-methyltesterone increased the urinary excretion of the ketone bodies. The urinary excretion of ketone bodies was higher than when either alone was given. The serum ketone bodies increased after the treatment with Δ' 17α-methyltestosterone but was not affected by high-fat diet. 3) Administration of propionic acid resulted in an elevation of the fasting blood glucose and impaired the glucose tolerance. These effects were found more evident in the former than the latter. Lactic acid did not have these effects. Addition of beef tallow made these effects more prominent. 4) Oral administration of 17 a-methyltestosterone or short-chain fatty acids (propionate, butyrate and lactate) caused a reduction in liver glycogen. 5) Adminirtration of beef tallow increased the lipid deposition of hepatic cells. This finding was also found in the group where Δ' 17α-methyltestosterone was added to the standard diet. 6) Fasting for 5 days caused an elevation of blood sugar and an impairment of glucose tolerance. An injection of purified human depot fat made these changes more remarkable. 7) On the basis of these observations, a discussion was made whether the acceleration of lipid metabolism might play an important role in diabetogenesis or not.
Lipid and carbohydrate metabolism in diabetics were compared with those in obese subjects, patients with hyperlipemia and aged normal persons and an etiological relationship between the development of the diabetic state and an abnormal lipid metabolism was studied. The experiments gave the following results. 1) The levels of the fasting non-esterified fatty acids in the serum was significantly elevated with degree of obesity but there was not such a correlation in β-lipoprotein, total cholersterol, triglyceride or phospholipids. 2) The NEFA in the serum was measured in the fasting state, at 30 min.and at hourly intervals for 3 hours after the intravenous injection of 0.5g of glucose per kg body weight (Glucose-NEFA Test).The NEFA in the serum was transiently decreased by this glucose loading. a) The fasting NEFA in the serum of obese subjects and those having coronary disease with hyperlipemia were significantly higher than normal and emaciated groups. b) In the diabetic group, the fasting NEFA in the serum was highest and the NEFA response after glucose loading was most delayed. c) The NEFA response of the aged group above 65 years of age was similar to that of diabetics. 3) When 9 mg of Δ'17α-methyltestosterone per kg body weight was administered orally to twenty patients with hyperlipemia, following changes were observed. a) Among serum lipids, triglyceride prominently decreased.The fasting blood sugar was elevated and glucose tolerance was impaired. b) In 7 of the 20 cases a diabetic state was caused.The values for serum triglyceride of this group before treatment with Δ'17α-methyltesterone were significantly higher than those of the group whose glucose tolerance remained normal.The reduction of serum triglyceride in the former was also significantl yhigher than that of the latter. There was no significant different in the periods of administration. c) The Glucose-NEFA Test showed a significantly delayed NEFA response. d) The concentration of serum ketone bodies was elevated and urinary excretion of these was increased.These two values almost reached to those observed in diabetic patients. 4) Based on these results, it was suggested that abnormality of lipid metabolism, especially accelerated catabolism of fatty acids, played an important role as a precipitating factor in some of the diabetic patients.
Plasma insulin responses to intravenous injection of glucose (0.4g/kg) and xylitol (0.4g/kg) were compared in five anesthetized dogs.After glucose injection plasma glucose increased immediately up to 237±14mg/dl, which returned to the fasting level in about 45 minutes, and plasma insulin rose promptly from the fasting level of 19±9μU/ml to the peak value of 68μ11μU/ml, which was observed between 0 and 10 minutes. Injection of xylitol caused a slight temporary increase in plasma glucose, then in four dogs a decrease below the fasting level.Plasma insulin concentration increased quickly to a very high peak of 188±27 μU/ml, which occurred between 10 and 20 minutes after xylitol injection. The mechanism and physiological significance of this effect of xylitol are unknown, however it is suggested that xylitol may be a useful tool for the study of mechanism of insulin secretion.
The total number of children of all employees of Yawata Iron and Steel Works was 44, 144 in 1964. All protocols of the children treated by physicians in this year were picked up by us, and four overt diabetics were found in the protocols.These 4 diabetics were reexamined and diagnosis of them were confirmed by us.The prevalence of diabetics in the total children was 1: 10, 000.
Angiopathy such as retinopatey and/or nephropathy as sequelea of peripheral arteriolosclerosis is one of the most important problems for prognosis of diabetes mellitus.The pathogenesis of the development of these vascular complications in diabetics, however, has not yetbeen fully defined. Recently, the metabolic disorder of glycoprotein is emphasized in diabetic states with special reference to the vascular complications.Retinal microaneurysm and/or intercapillary glomerulosclerosis were found to possess marked deposition of PAS-positive and metachromasy negative substance supposed to be glycoprotein by histochemical examination. Several authors reported that the levels of hexosamine, hexose and sialic acid, which were contained in protein bound carbohydrates, rised in the serum of diabetics, particularly with angiopathy, In the present study the authors intended to analyse serum protein bound carbohydrates and electrophoretic fractions of glycoprotein using cellulose acetate membrane in patient with diabetes mellitus and simple obesity. 1.Serum protein bound hexosamine and sialic acid of 43 diabetics increased compared with those in 38 non diabetics.Among non diabetic subjects, obese subjects showed almost the same to that of diabetics and were higher than that of subjects keeping ideal body weight. 2.There were no correlations between protein bound carbohydrates and fasting blood sugar level, duration of diabetes or vascular complications which were checked by funduscopic examination, renal function test and others in diabetics. 3.The electrophoretic pattern of protein bound carbohydrates in diabetics was not different significantly to that in non diabetics in percentage, therefore the elevated amount in each fraction was seen in diabetics.
The 50 g oral glucose tolerance test, electroretinographic and fluorescein-potographic examinations were carried out in twenty subjects whose father and mother were both diabetic. The glucose tolerance test was normal in ten, borderline in five, and diabetic in five of the cases. If the glucose tolerance test was not diabetic, we defined the cases as prediabetic.The oscillatory potential decreased in eight of the fifteen prediabetic cases who had normal a- and b-waves in electroretinogram and a normal fluorescein fundus photograph. These findings suggest that unknown retinal (metabolic) changes occur in prediabetic state in which any abnormality can be detected by other methods used today.