Clinical and experimental studies on the insulin-like activity and glucagon-like activity of blood were carried out from the view point of metabolic and neurogenic controls of the endocrine activity of pancratic islets.
Insulin-like activity of blood was determined by Shimazu's rat diaphragm method and glucogon-like activity by Shinko's liver slice method. As the metabolic factors, the following three hexose, i.e., glucose, levulose and galoctose were employed by means of intravenous infusion and by oral administration.
In clinical investigations, normal and diabetic subjects were examined with simultaneous follow-up of blood sugar level. In animal experiments, both normal and alloxan dogs of 7-10kg. body weight were used.
Blood was drawn from V. pancreaticoduodenalis sup., A. femoralis and V. femoralis and blood sugar level was determined by Hagedorn Jensen's method.
The results are summarized as follows ;
1) In normal and diabetic subjects per oral administration of glucose induced an increase of insulinlike activity of blood. The one hour percent increase of this activity in normal subjects was more pronounced than that of diabetics.
The diabetics who do not require insulin showed higher percent increase of insulin-like activity than the diabetics under insulin treatment.
2) Following intravenous infusion of glucose solution insulin-like activity of blood showed transient decrease and then turned to increase in normal subjects. The author has assumed, that this indicates a possible acceleration of insulin secretion by an initial consumption of blood insulin by infused glucose. In diabetics this transient decrease of insulin-like activity disappered with increasing severity of the disease, showing direct increase immediately following glucose infusion.
The glucagon-like activity of blood of normal subjects showed a transient increase in 30 minutes after infusion of glucose solution but returned to preinjection level in 60minutes.
In diabetics, however, with the increasing severity of the disease, this normal pattern of glucagon was lost. It decreased transiently at first and then increased upon glucose infusion.
3) Investigations on normal and alloxan dogs in case of intravenous infusion of glucose solution revealed almost the same pattern as normal subjects and diabetics as regard to the insulin-like activity of blood. The pattern of blood insulin-like activity showed slight modification following the insulin consumption in the blood.
Glucagon-like activity of blood showed no particular change both in normal and alloxan dogs. In general, one can say that alloxan dogs tend to secrete glucagon rather slowly than normal dogs.
After infusion of glucose solution an increase of A-V ratio was observed, resulting most plausibly from the increased glucose uptake in the peripheral tissue under the co-influence of insulin and glucagon.
4) In case of infusion of galactose solution blood glucose decreased parallel to the increasing value of the total blood hexose.
There was a similar patten of insulin-like activity and glucagon-like activity of blood as in the case of glucose infusion.
Thus, galactose seems to promote glucagon secretion, insulin consumption and subsequent insulin secretion. A-V ratio also showed increase on galactose infusion.
5) No paticular change of insulin-like activity or glucagon-like activity of blood was observed on levulose infusion. This seems to indicate that insulin is not necessarily required for metabolism of levulose.
Total hexose of blood showed no corresponding increase after levulose infusion. This seems to indicate the relatively quick break down of levulose after infusion. A-V ratio showed no increase on levulose infusion.
6) Electrical stimulation of Vagal Nerve brought about no regular increase or decrease of insulinlike activity of blood drawn from V. pancreaticoduodenalis sup..

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The correlation between female gonads and pituitary-thyroid system has been discussed very often in the realm of endocrinology and gynecology. As regard to the influence of male gonads upon pituitary-thyroid system there are still many discrepancies of opinion about the result of experimental studies. One of the reasons of such diverse opinions consists in the lack of an appropriate method for the direct measurement of thyrotropin (hereafter abbrev. as TSH) activity in blood. Ogura et al. of our clinic developed a new method for the direct measurement of plasma TSH activity using I¹³¹-release method of calf thyroid slices with Warburg apparatus.
The author therefore tried to study the influence of castration and male hormone administration, i.e., testosterone propionate (abbrev. as T.P.) and Methylandrostendiol (abbrev. as MAD) upon the plasma TSH activity of normal and thyroidectomized dogs with Ogura's method. The serum PBI level was also determined on normal and castrated dogs, further more on castrated dogs treated with T.P. successively using Barker's method.
The results are summarized as follows :
1) The castrated male adult dogs showed a transient elevation of plasma-TSH activity up to the 9th day after castration. A rather sharp decrease of plasma-TSH activity was observed thereafter, reaching it's lowest limit in postoperative 30-60days. The plasma-TSH level then turned to increase but it remained still in subnormal level even 120 days after castration.
2) The plasma-TSH level of thyroidectomized dogs showed marked increase after the operation. If these thyroidectomized dogs are castrated, the elevated plasma-TSH volue turns directly to decrease, showing no transient increase, which was observed on nonthyroidectomized dogs. The plasma-TSH value reached the lowest level in between 8-14 days after castration, then it began to increase gradually but even 100 days after castration it remained still in a lower level than preoperative niveau.
3) Injection of T.P. to the male castrated dogs produced elevation of plasma-TSH value. Simultaneous observation of serum PBI showed also an 'elevated value. The most marked increase of plasma-TSH was observed with single injection of testostererone heptanoate in doses of 5.0mg/kg of body weight, then T.P. 1.0mg/kg/day and 0.5mg/kg/day for three successive days followed the former. Single injection of T.P. in doses of 1.0mg/kg, 5.0mg/kg and 0.1mg/kg brought about also a slight increase of plasma-TSH value in order.
4) The castrated dogs responded with greater percent inerease of plasma-TSH upon the injection of T.P. as compared with the castrated-thyroidectomized dogs. A Plausible explanation of this phenomenon was sought in the lowered reactivity of elevated plasma-TSH of the thyroidectomized dogs.
5) The decrease of plasma-TSH value on the castrated dogs and the increase of the value upon injection of T.P. are most plausibly explained from the antagonism of TSH-producing activity and gonadotropin-producing activity of anterior pituitary.
6) Injection of MAD showed no apparent influence upon the plasma-TSH level of male castrated dogs and castrated-thyroidectomized dogs. MAD seems to have no effect upon pituitary-thyroid system.
Following the report I, the behavior of thyroid gland under castration or male hormone administration was observed. Normal and castrated adult male dogs under thyroid-constant feeding were used in the following experiment to observe the behavior of the thyroid gland. The thyroid gland was totally resected under Isozol-anesthesia and the following examinations were carried out on them.
1) Papar radiochromatography of the iodinized amino acid fractions of the thyroid gland.
The gland was homogenized with NH₄OH-NH₄C1 buffer, then digested with trypsin and urea.' The butanol extract of trypsin digest was examined on paper-radiochromatography.

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We prepared β₁-lipoprotein from human diabetic serum and studied its diabetogenic action. The Following results were obtained.
1) Intravenously injected insulin I¹³¹ was retained in the blood of diabetic patients with and without insulin treatment.
Therefore, it was suggested that diabetics had common unknown extracellular factors in their serum which impeded the distribution of insulin I¹³¹ to the tissue. At the same time, the blood sugar reduction by insulin was lower in diabetics than in normals.
2) Diabetic β₁-lipoprotein inhibited the glucose output of rat liver-slices and the glucose uptake of rat diaphragms, but in normal ones it accelerated both.
3) Diabetic β₁-lipoprotein inhibited the binding of insulin I¹³¹ to liver, kidney and muscle slices of rats. Consequently it was suggested that the retardative factors of insulin I¹³¹ in blood might be diabetic β₁-lipoprotein.
4) Diabetic β₁-lipoprotein intravenously injected, was more distributed than normal to target organs, and the blood concentration of the former was lower than that of the latter. These findings were in contrast with the concentration curve of insulin I¹³¹ (mentioned in 1).
At this experiment, after an injection of diabetic β₁-lipoprotein the blood sugar increased but decreased after normal.
5) The greatest amount of injected diabetic β₁-lipoprotein I¹³¹ distributed to cell membrane and was not washed out by diffusion.
Therefore, chemical binding of lipoprotein with cell membrane was thought to be the reason.
6) According to the above mentioned findings, it was thought that, Diabetic β₁-lipoprotein intravenously injected, rapidly bound with cell membranes of target organs of insulin and thus inhibited the active transport of glucose of insulin and elevated the blood sugar level.
7) By an intravenous injection of diabetic β₁-lipoprotein blood sugar was slowly increased and reached its maximum after 4 hours of injection and after 6 hours hyperglycemia still continued. By daily injection, continuous hyperglycemia was obtained.
The mechanism of hyperglycemia was thought due to the inhibition of peripheral glucose utilization.
8) An intravenous injection of diabetic β₁-lipoprotein inhibited the action of insulin and elevated the blood sugar level.
9) By the use of infrared-spectrophotometry, it was observed that diabetic β₁-lipoprotein did not contain any unknown substance and the proportion of chemical composition of its fraction was not abnormal.
10) As the result of chemical analysis of diabetic β₁-lipoprotein, cholesterol, phospholipid, neutral fat and protein were slightly larger in quantity than normal.
11) By the use of metachromasy of methylorange it was made clear, that the protein fraction of diabetic β₁-lipoprotein was different from normal.
Therefore the structure of protein of diabetic β₁-lipoprotein seemed to be abnormal.

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