1. In this paper, two cases of hyperinsulinism were discribed.
2. Disturbance of consciousness and abnormality of EEG showing slow wave and high voltage appeared frequently particularly in fasting state. The lowest blood sugar level examined in the first case was 29mg% and in the second 44mg%.
3. No hypofunction of anterior pituitary, thyroid gland, adrenal cortex and medulla, and no disturbance of liver function were observed in these cases. Increased insulin like activity of serum was observed in both cases by rat diaphragm method. From these findings both cases were clinically diagnosed as organic hyperinsulinism. Therefore, the surgical treatment for pancreas was performed in both cases.
4. In the first case, a capsulated tumor (3.2×3.4×2.2cm, 14, 29) was found in the tail of pancreas, and after removal of this tumor hypoglycemic attack disappeared. The tumor was islet cell adenoma and contained 421.4units of insulin (29.6u/g of this tumor). Five months after the removal, the glucose tolerance test showed diabetic curve.
In the second case, tumor was not found, but hypoglycemia was improved by partial resection of pancreas (three fifth of pancreas). Extractable insulin concentration of the resected pancreas of the second case was higher than that of the normal pancreas.
In addition, histologic examination of this tissue proved hyperplasia of islet cells. These findings might show the hyperfunction of islet cells in the second case.
5Urine catecholamine level elevated in both cases, but after surgery catecholamine level falled into within normal value in the first case. In addition, eosinopenia, unstable state of autonomic nervous system, and hyperglycemic effect of patient's serum in the adrenalectomized mice were all disappeared in the first case after the removal of the tumor.
6. Skin test with insulin, extracted from the islet cell adenoma of the first case, was negative in both cases. Precipitation test with the same insulin and insulin bindlng test with insulin I¹³¹ were negative in the first case. Moreover, skin test and precipitation test with the bovine regular insulin were negative in both cases. Antibody to human and bovine regular insulin was not proved in both cases.

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In this report insulin neutralizing activities of antisera of guinea pigs and rabbits, and change of serum ILA before and after glucose loading in several diseases with metabolic abnormality of glucose were studied. Serum ILA was measured with technique by Renold et al. and indicated as glucose uptake mg/g of epididymal adipose wet tissue weight.
Insulin standard curve; In following concentration, from 15 to 1000 microunits/ml, response curve was linear (λ=0.35). Guinea pigs were immunized with insulin Freund's adjuvant, and rabbits with insulin bis-diazo-benzidine (BDB) sheep erythrocytes.
It had shown that all of antisera of guinea pigs had high neutralizing activities, max. 1000 microunits/ml, in vitro with this method, but of rabbits showed less neutralizing activities, however high BDB hemaggultination titres. Peritoneal injection of antisera of guinea pigs caused markedly hyperglycemic reactions in Wister rats.
Studies on change of serum ILA in several diseases;
i) In diabetes, after glucose loading, bloodsugar curve was hyperglycemic and the time of peak of serum ILA was late and/or showhd low responsiveness, especially in juvenile types and some cases with ketosis.
ii) In acromegaly, showing normal bloodsugar levels, serum ILA in both fasting and after glucose loading were high.
iii) In steroid diabetes, serum ILA was low and/or peak was so late as diabetes mellitus.
iv) In hyperthyroidism, no clear change of serum ILA or correlation between bloodsugar and serum ILA was shown.
v) In addison disease and hypophyseal insufficiency relative hypoglycemia and low serum ILA were observed.
vi) Langerhans islet cell adenoma showed high value of fasting serum ILA with hypoglycemia and hypoglycemic coma after intravenous Tolbutamide test, then bloodsugar level fell down markedly to 18mg/dl

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Incidence and progression of diabetic retinopathy with special reference to the degree of control of diabetes were investigated in patients attending our diabetes clinic.
All the necessary data concerning history, physical and laboratory examinations were obtained in 624 untreated cases at the begining of the visit. Diabetic retinopathy was found in about 10 per cent of the patients when the duration of diabetes was estimated to be under 1 year.
This incidence, however, became greater as the duration of the disease was prolonged, without regard to the age of the patients, thus exceeding 50 per cent when the duration was more than 10 years. Incidence of retinopathy was lower among patients whose fasting blood sugar before the treatment was under 140mg/dl, irrespective of the duration of the disease.
Remarkable increase in the incidence was observed, however, not only with the prolongation in duration of the disease, but also with the increment in pre-treatment fasting blood sugar level.
Careful follow-up of fundi, examined exclusively by specialists, were performed in 227 patients who had been under constant medical observation including necessary laboratory examinations.
It is to be emphasized that control of diabetes was determined in our study entirely on the basis of fasting blood sugar which was repeatedly determined whenever patients visited our clinic at intervals ranging in almost all the cases between one and 4 weeks. Control of diabetes was judged “good” when 80 per cent or more of the fasting blood sugar remained below 139mg/dl with Hagedorn-Jensen method.
On the other hand, judgement of “poor” control was made when more than 50 per cent of the fasting blood sugar was higher than 170mg/dl. So-called labile type was included in this group. “Fair” control was defined as the intermediate between these categories.
Incidence of patients with appearnce of retinopathy during the period of observation or with progress of diabetic retinopathy based on Wagener's classification were studied.
Significant difference was already noted after the first 2 years. Incidence of progression of diabetic retinopathy became gradually higher when control became worse in the order of good, fair and poor.
It is also to be stressed that the progression of retinopathy was minimized even in patients with higher fasting blood sugar level before treatment, so long as good control was obtained.
This difference in progression of retinopathy became even more marked when the period of observation was increased to 4 and 6 years.
The incidence of progression. was also significantly higher in patients over 50 years of age compared with those under 49 years of age at the time of first visit.
Blood pressure, arteriosclerosis of the retina and levels of serum total lipid were found to have no significant correlation to the progression of retinopathy.
In order to inhibit or to prevent progression of diabetic retinopathy, importance of strict control especially in younger patients with diabetes was emphasized.

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The autopsied fifty-five diabetic patients and fifty-nine non-diabetic controls were studied from the point of view of circulatory disturbance of the nutrient vessels and pathologic change of the nerves.
None of the controls had any malignant hypertension, peripheral nervous disease, and heart disease.
In all, 41 plexus brachialis (pars subscapularis), 45 vagal, 19 sciatic, and 21 femoral nerves of the diabetics were studied microscopically in cross section and and partly in longitudinal section.
The author investigated the arteriosclerotic changes of the large arteries (subclavicular artery, abdominal main artery, carotid artery & iliacal artery), observed microscopically the arteries (50-500μ in diameter) & arterioles (50μ in diameter) of the peri and intraneural vessels, according to the criteria of Blumenthal, counted the number of intraneural capillary blood vessel/mm2 and considered the relation between diabetic complications.
The results were as follows:
1) In the arterioles of the peripheral intraepineural nerves, the narrowing of the lumen of the arterioles of diabetics is marked in comparison with those of non-diabetics.
2) The number of capillary blood vessel/mm2 in diabetic nerves is decreased. And this change was seen in plexus brachialis, vagal and sciatic nerves.
3) Among diabetics, the above-mentioned observations are remarkable in the cases with diabetic complications.
4) The myelin sheath degeneration and the diffuse fibrosis of the peripheral nerves are more frequent in those of diabetics. Especially the changes of marked diffuse fibrosis or fatty degeneration are seen for the most part in the diabetic cases.
5) These histologic changes are mostly seen in the cases with clinically manifest symptoms of nervous disturbance, but sometimes seen in the cases with clinically latent symptoms, not only in the nerves which corresponds to the symptoms but also in those of upper extremities and lower extremities which do not always correspond to the symptoms, including autonomic nerves.

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I¹³¹ labelled-insulin has been administered in tracer doses to rats and rabbits, intravenously or intraperitoneally.
Firstly, the localization of insulin-I¹³¹ into organs was investigated. Injecting intravenously, the kidneys, liver and also muscles were found to be the major regulator of the fate of injected insulin-I¹³¹, whereas there was no affinity to the brain. Injecting intraperitoneally, in the experiment, it was clearly revealed that affinity of insulin-I¹³¹ to the muscles was increased rather than that of administered insulin-I131 by intravenous injection.
Secondly, it was found that the major portion of the intracellular insulin-I131 was bound to mitochondria and microsome fraction, but not to nuclear fraction.
In conclusion, the significance of these investigations was discussed on the role of administered insulin-I131 in reference to insulin action or to its metabolism.
The posibility that the mechanism of insulin action, as a whole, will be connected with intracellular particles, particularly with mitochondria, will remain to be solved in the future.

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