IRI responses to successive pulses of arginine and glucose or glucose and arginine given at an interval of 30 minutes were investigated in healthy male volunteers under constant intravenous infusion of 5% glucose, 20% glucose or 10% arginine soultion for 2.5 hours.
The results were as follows:
1) On the infusion of 5% glucose solution during which the basal blood sugar remained within fasting levels, IRI increments (ΔIRI) induced by either arginine or glucose pulse were significantly enhanced by prior heterogenous pulses given 30 minutes before the pulse.
2) On the infusion of 20% glucose solution during which the basal blood sugar reached a level near 200 mg/100ml, IRI responses to arginine pulses were significantly increased compared withthose in the group with 5% glucose solution, irrespective of administration of a prior glucose pulse.
Synergism between arginine and glucose pulses in the induction of insulin secretion, however, was no longer observed in this group: neither glucose nor arginine as a prior heterogenous pulse significantly affected the IRI response to the second pulse.
3) During the infusion of 10% arginine solution, IRI response to glucose was significantly enhanced by a prior arginine pulse. 4) IRI increments induced by arginine pulses showed a significant correlation to the blood sugar levels at the time of arginine load.

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Rat epididymal adipose tissue was incubated in sera from diabetics and patients with cirrhosis of the liver in conditions with 60 and 600μU/ml of added insulin as well as without added insulin, and the incorporation of ¹⁴C from I-¹⁴C acetate into both whole and individual fatty acids was compared with those found in normal human serum and Krebs-Ringer bicarbonate buffer.
The results were as follows:
1) The incorporation of ¹⁴C from I-¹⁴C acetate into whole fatty acids of adipose tissue in each serum was inhibited as compared with that in buffer; moreover, the synthesis of fatty acids was low in the sera from diabetics and particularly in the patients with cirrhosis of the liver in conditions with less than 60μU/ml of added insulin as compared with those found in the normal human serum. On the other hand, the synthesis of whole fatty acids in every serum was inhibited by more than 20% as compared with that found in buffer in cases with 600μU/ml of added insulin.
2) The percentage of recovered cpm incorporated into discrete fatty acids showed some differences in these sera as compared to the values in buffer. The percentages of recovered cpm in 14: 0 and 16: 1 in every serum were lower than those found in buffer independently of added insulin concentration, however, the percentage in both sera from diabetics and patients with cirrhosis of the liver showed some inhibition as compared to values found in normal serum under conditions with added insulin.
The percentage of recovered cpm in 16: 0 in every serum showed increase of more than 20%, and about 10% in conditions without added insulin and with 60μU/ml of added insulin, as compared to the values in buffer, respectively. However, the percentage of 16: 0 in each serum decreased to the nearly same value as in the buffer in the presence of 600μU/ml of added insulin. Besides, the percentage distribution of 16: 0 in the sera from diabetics and patients with cirrhosis of the liver was lower than those found in the normal human serum under conditions with less than 60μU/ml of added insulin. Therefore, it is possible to conclude that the change in the synthesis of 16: 0 quantitatively reflects most strikingly the change found in the formation of whole fatty acids, because ¹⁴C in this fatty acid accounts for 50-64% of total labeled fatty acids.
Tne percentage of recovered cpm in 18: 0 in each serum increased by 20-45% independently of added insulin concentration compared with the value in buffer, and in addition, no special differences were found among sera.
The percentage of recovered cpm in 18: 1 in every serum increased by 10-20% as compared to the value in buffer in conditions with less than 60μU/ml of added insulin, but remarkable inhibition was found in the presence of 600μU/ml of added insulin, and the inhibition was stronger in the sera from diabetics and patients with cirrhosis of the liver than in the sera from normal subjects.
On the other hand, the synthesis of fatty acids with retention time corresponding. to 20: 0 or longer showed a compensatory relative increase for the depressed formation of 16: 0 or 18: 1 in every serum with 600μU/ml of added insulin.
From these results, the depressed synthesis of 16: 0 and 18: 1 in each serum, particularly in the sera from patients with diabetes and cirrhosis of the liver, was considered to be responsible for the inhibition of insulin effect by these sera.

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Fifty five consecutive autopsy cases of primary diabetes at Saiseikai Central Hospital and sixteen cases of typical myocardial infarction in primary diabetes who were not autopsied or survived myocardial infarction were divided into 3 groups to study their differences.
I: Myocardial infarction (MI) group (22 patients who developed MI)
II: Latent MI group (6 patients who had scattered small necrosis in myocardium at autopsy, although they had no evidence of MI clinically)
III: Non MI group (43 patients with no muscle necrosis at autopsy)
Patients with fasting blood sugar of 201mg/dl or more at initial examination, patients whose fasting blood sugar could not be controlled mostly under 201mg/dl, patients with weight less than the ideal weight at initial examination, and the patients treated predominantly with insulin, were noticed less frequently with statistical significance (p<0.05) in the MI group than in the non-MI group. Patients with fasting blood sugar controlled mostly under 130mg/dl, patients treated predominantly by oral hypoglycemic agents, patients who were obese at initial examination, patients whose weight was not controlled under ideal weight, patients with hypercholesterolemia, and patients with cardiomegaly, were noticed more frequently with statistical significance in the MI group than in the non-MI group. Patients with glomerulosclerosis and patients with diabetic retinopathy were noticed more frequently with statistical significance in the latent MI group than in the non-MI group. We then studied the “risk factor” of MI and latent MI using 55 autopsy cases only, which we considered as randomised primary diabetics. MI was found to have developed more frequently with statistical significance in patients treated with oral hypoglycemic agents than in patients treated with insulin. MI tended to have developed more frequently in the poor weight control group than in the good control group (p<0.1). The development of MI did not have any significant correlation with fasting blood sugar on initial examination, fasting blood sugar control, the level of serum cholesterol, or the presence or absence of glomerulosclerosis and diabetic retinopathy. Latent MI (scattered type necrosis) was found more frequently with statistical significance in patients with glomerulosclerosis or diabetic retinopathy than in patients without them.

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The serum carboxypeptidase A activity (CPase) was measured in various types of patients with glucose intolerance using Okuda's colorimetric method. The relationship among CPase and the duration of diabetes mellitus, control of glucose intolerance and fasting serum IRI levels were also studied. The following results were obtained.
(1). The mean CPase in 21 normal subjects was 289.2±3.8 unit (U). (mean±SE), and no correlation was found between CPase and the age of the patients. CPase in 25 cases of adultsonset type and 14 cases of juvenile type diabetes mellitus were 257.6±6.5 U and 248.0±22.8 U respectively. CPase in 8 cases of pancreatic cancer with glucose intolerance whose diagnosis was verified by laparotomy and that in 12 cases of diabetes mellitus with liver cirrhosis were 182.9 ±6.0U and 210.8±11.6 U, respectively.
(2). No significant correlation was observed between CPase and the duration of diabetes mellitus. However, CPase levels were markedly low in cases of diabetes mellitus of long duration.
(3). Marked decrease in the level of CPase was not observed in patients with diabetes mellitus who were under good control. On the other hand, markedly low levels of CPase were often observed in patients with pancreatic cancer also having glucose intolerance and in diabetics with liver cirrhosis who were well controlled.
(4). In patients with diabetes mellitus, No significant correlation was observed between CPase and fasting serum IRI levels.
The determination of CPase seems to be a useful screening method for pancreatic damage in diabetics, and it also seems to be a useful test for diabetics in relation to clinical history and the degree of diabetic control.

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The isolated perfused rat liver preparation has been used to study the effects of fasting and liberal feeding against the action of sulfonylureas on hepatic metabolism.
Livers were taken from male rats of the Wistar strain weighing 200 to 300g. They were fed ad libitum or fasted for 18 hours prior to perfusion. The initial recirculating solution used was 250 ml with Krebs-Ringer bicarbonate buffer containing 2.5% bovine albumin, 10 mM glucose and 25% bovine erythrocytes prepared as reported previously. Tolbutamide was added in the medium after 30 minutes pre-perfusion. However, exogenous lactate was perfused without pre-perfusion.
1) It was found that tolbutamide directly suppressed glucose production and ketone body formation by the isolated fasted rat liver, but that it failed to reduce these metabolites in the fed rat liver.
2) Glucose production was minimally increased in livers from fasted or fed rats perfused with lactate. It was found that lactate markedly suppressed ketogenesis in livers from fasted rats, but that it increased ketogenesis in livers from fed rats.
3) The degree of utilization by the livers of added lactate was immediately and markedly increased after the start of perfusion in livers from fasted rats. However, there was a lag time before the utilization of added lactate started in livers from fed rats as compared with those from fasted rats. No differences were found as regards changes in LIP ratio between fasted and fed rat livers.

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The effect of glucose on arginine-stimulated glucagon and insulin secretion was studied in perfused rat pancreas prepared by the modified method of Grodsky. The isolated rat pancreas was perfused with 4.5% dextran KRBB containing glucose over 60 minutes. Twenty minutes after the start of glucose perfusion, 5% arginine solution was injected during twenty minutes via a side arm at the rate of 0.2ml per minute. The increases of insulin and of glucagon in the effluent at the two minute period of arginine injection were 43.2±3.5 to 86.4±6.2ng/m/ and 40±3 to 510±21pg/ml, respectively, when the perfusate contained 300mg/d/ of glucose. They were 21.3±2.4 to 39.0±3.3ng/ml and 126±8 to 3433±127pg/ml, if the perfusate contained 150mg/dl of glucose, and 2.0±0.3 to 32.4±3.2ng/m/ and 525±18 to 2062±106pg/ml if the perfusate contained 50mg/dl of glucose, respectively. The perfusion of glucose free solution containing arginine provoked a slight increase in insulin (2.1±0.2 to 10.7±1.6ng/ml) and glucagon (625±23 to 745±46pg/ml). These results showed that glucose might be necessary for arginine stimulated glucagon and insulin secretion in the perfused rat pancreas.

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A 64-year-old female was admitted because of right upper abdominal pain. She had complained of a bout of colic pain at the right hypochondrium three years prior to admission and a diagnosis of gall stone was made. Glucosuria was found nine years before admission and since then, she had been treated irregularly with oral anti-diabetic drugs or insulin.
On the 21st day of admission, insulin in amount of 0.1 U per kg of body weight (5.1 U) was injected intravenously in order to investigate responsiveness to insulin. Immediately after the insulin injection, the patient showed nausea, vomiting, a fall of blood pressure, a loss of consciousness and shock, which continued for 20 minutes and were relievee by the administration of epinephrine and prednisolone.
Skin tests performed one month after the anaphylactic episode showed strong positive reaction for beef and pork insulin but very weak reaction for bonito insulin.
During and after the operation for gall stone, her diabetic state was successfully controlled by bonito insulin.
Insulin binding antibodies were demonstrated in her plasma after the operation, and showed reaction to beef insulin but little reaction to bonito insulin.
The occurrence of reaginic antibody to insulin and diabetic control with bonito insulin were discussed.

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