Although studies on the relationship between hormones and VB₂ have been chiefly made regarding by sexual-hormones, however there are only a few of them who treated the activities of hormones such as pituitary glands, thyroidal gland, suprarenal gland and testis.
Hence, author studied the riboflavin metabolism in liver of rats.
The results obtained were as follows.
1. In the case of hypophysectomized rats, a significant increase of riboflavin in liver was found in all cases.
2. In the thyradin injected group or the merkazole injected group (hypothyroidism) did not show any difference in the change of VB₂.
3. In the adrenalectomized group, the change of VB₂ in liver always decreased but after the administration of cortisone, it did not show remarkable change, it was just the same as those in the normal case.
4. In the case of cortisone administration to normal rats, this did not produce any noticeable change.
5. After the intramuscular injection of ACTH to the adrenalectomized rats, a slight increase of VB₂ in liver was detected.
6. In testisectomized group there appeared a remarkable decrease of VB₂ in liver, but it recovered by the administration of testosterone, estrogen and bothermon (testosterone + estradiol). And furthermore investigated testosterone showed the maximum value of increase.
7. The administration of testosterone to the normal rat, showed a tendency of slight increase of VB₂ in liver.
8. VB₂ concentration in liver by the administration of VB₂ into testisectomized rats was always more than in the VB₂ injected normal group.

View full abstract

For pathophysiologic studies on diabetics with special reference to the functional activities of pancreatic islets, the most reliable method of studies is the routine followups of blood levels of pancreatic hormones, i.e., insulin and glucagon. Owing to the technical difficulties, no direct estimation of both hormonal activities in the blood could be obtained until quite recently.
In the 2nd Medical Department of Kobe Medical College, members of the research staff investigated the Insulin-like activity and Glucagon-like activity of blood (hereafter abbreviated as Insulin-value and Glucagon-value) with the rat diaphragm method and with the rat liver slice method. (Shimazu : The Japanese Journal of Gastro-Enterology, 57 827, 1960., Shinko : reported before the first ASIA and Oceania Regional Congress of Endocrinology in 1959.).
The author has tried to clarify the mode of hormonal and nutritional control of endocrine activity of pancreatic islets by using these methods.
As nutritional extra factors, the infusion of Amino-acid preparations and Fat emulsions were used.
The results of various clinical and experimental observations are summarized as follows :
1. Intramuscular injection of 15 to 30 units Growth hormone to kittens, induced an elevation of Glucagon-value and a decrease of Insulin-value in 30 minutes. This phenomenon was more conspicuous with higher Growth hormone doses.
2. An injection of 30 to 50 units Growth hormone to normal dogs brought about an increase of Glucagon-value as the first step, followed by an increase of Insulin-value This was more conspicuous with higher Growth hormone doses. The blood sugar rate showed no regular increase or decrease as compared to the hormonal hypersecretion or hyposecretion.
3. Continuous intravenous drip of 5 to 15 units ACTH to dogs for 60 minutes induced no regular hormonal response from the pancreatic islets and effected no change of blood sugar level. Thus the single injection of ACTH seems to influence no regular response.
4. Intramuscular injection of 25 units ACTH to normal subjects induced an elevation of Glucagon-value and a lowering of Insulin-value in 2 hours, but in 3 hours these values returned to the pre-injection level.
5. Growth hormone, ACTH and Hydrocortisone were administered by in ramuscular injections for 6 to 8 days in dogs and then they were treated with continuous drip of 250c.c. 5% glucose solution. The responses of Insulin-value and Glucagon-value were determined simultaneously with the blood sugar response. Insulin-value showed a slight increase or almost no response, whereas Glucagon-value showed the high starting level from which no further distinct increase or decrease was observed.
ACTH-treated dogs showed an elevation of Glucagon-value and blood glucose level following the drip and they nearly returned to the pretreatment level. Simultaneous observations of Insulin-value revealed no regular increase or decrease.
Hydrocortisone-treated dogs showed an elevation of Glucagon-value in parallel with the elevation of blood sugar level, whereas Insulin-value showed a decrease. The reverse change wasobserved in Glucagon-value and Insulin-value as the blood sugar level went down.
6. Diabetogenicity of Growth hormone, ACTH and Hydrocortisone were compared with cach other from the aspect of Insulin Mobilizing Index formulated as follows :
Insulin Mobilizing Index=_ (A-V one hour after glucose loading) - (A-V before glucose loading) Median blood glucose value× 100 where A-V means arterial blood glucose value-venous blood glucose value.
Lowest Insulin Mobilizing Index was observed with Growth hormone, ACTH came next and with Hydrocortisone, an almost normal value was observed.
7. From the observation of Insulin-value and Glucagon-value in case of various endocrine disorders and in dogs treated with Growth hormone, ACTH and Hydrocortisone respectively,

View full abstract

It was reported by K. Okamoto and his coworkers that disorders in the development of β-cells in Langerhans' islets are seen in offsprings obtained by mating rats of Wistar strain which had alloxan-diabetes for a long period. T. Tanaka reported on the duration of diabetization required in Wistar male rats to bring about damage of β-cells in their offsprings. To investigate the duration of diabetization required in female rats to cause a decrease in the number of β-cells in their offsprings and to investigate something further in male or female rats, the following experiments were done.
a) Wistar female rats with diabetic state induced by application of alloxan were mated with normal male rats after various durations of diabetization.
b) Females which, after having diabetes for over 40 days, were treated with insulin for varying lengths of time and were mated with normal males.
c) Males manifesting glycosuria for a period of 23 days, during which one-or two-day insulin treatment was given at various times were mated with normal females.
d) Females with glycosuria lasting for 24 days, which received insulin treatment either on the 1st or on the 14th day, were mated with normal males.
e) Normal males and females, whose Langerhans' islets were ascertained to be normal by an exploratory partial resection of the pancreas, were mated with each other. Thereafter the males were made alloxan-diabetic for over 40 days, and then mated with the same females that they had been mated with earlier.
The offsprings thus obtained, weighing over 150 g at the 90th day after birth, were sacrificed by ether. The Gomori's staining was applied on the pancreas, and histometrical examination was done on the number of β-cells in Langerhans' islets. The results obtained are summarised as follows :
1) In 30 normal rats (15 males, 15 females) the number of β-cells in one islet was found to be 65.4-70.4 (67.7±1.5 in average), the number of α-cells 14.0-19.6 (15.6±1.8 in average). There was no difference between males and females.
2) In experiment a), all of the young rats obtained by mating normal males and females, which had been in a diabetic state for 22 days (6 cases) or 23 days (10 cases), had the normal number of β-cells. The number of β-cells in all of the young, obtained from females with diabetes lasting for 24 days (6 cases), 25 days (6 cases), 26 days (5 cases), 27 days (5 cases) or over 40 days (10 cases), was decreased, the average number of β-cells being 58.3±0.78, 57.8±0.79, 58.3±1.1, 58.7± 0.75, 58.5±0.81, respectively. It might be concluded, therefore, that the diabetic state lasting for a period of the last 24 days of oogenesis, has an effect on female sexual cells that brings about a decrease in the number of β-cells in their offsprings.
3) In experiment b), the number of β-cells in all of the young obtained from females which showed no glycosuria for 3 days after 40 day diabetization (10 cases), was decreased (59.0±0.94 in average). In all of the young, obtained from females aglycosuric for 4 days (8 cases), 5 days (10 cases), 6 days (8 cases) or 7 days (9 cases), the number of β-cells was normal.
It is indicated that certain changes in oocytes, responsible for the decrease in the number of β-cells in the offsprings, disappear when the non-diabetic state lasts for the period of the last 4 or more days of oogenesis.
4) In expersment c), in all of the young obtained by mating normal females with males showing glycosuria for a period of 23 days, during which insulin treatment was given either on the 1st or on the 14th day (10 cases and 19 cases, respectively), the number of β-cells was normal. When the males were treated on the 2nd day, 9 of their 18 young were normal, the average number of β-cells being 67.1±1.4,

View full abstract

Recently it has been reported by K. Okamoto and his coworkers that disorders in the development of β-cells in Langerhans' islets are observed in the ofispring of Wistar strain rats with long-continued alloxan diabetes (both parents). It has also been reported that abnormalities are seen in the off-spring of normal females and males which have been diabetic for at least 23 days, or of normal males and females which have been diabetic for at least 24 days.
To investigate the duration of diabetes reqired to bring about disorders in the β-cells in offspring of both diabetic parents, the following experiment was performed.
Male and female rats of the Wistar strain with alloxan diabetes of varying durations were mated.
The offspring which weighed over 150 g on the 90th day after birth were sacrificed by ether. Gomori's stain was applied to pancreatic tissues, and the number of, and the area of β-or α-cells in Langerhans' islets were determined.
1) In 30 normal rats (15 males, 15 females) the number of β-cells in one islet was found to be 65.4-70.4 (average 67.7 ± 1.5), the area of β-cell was 108.9-118.3, μ² (average 113.1 ± 2.8μ²), the number of α-cells was 14.0-49.6 (average 15.6 ± 1.8) and the area of α-cell was 58.9-67.4μ² (average 62.6 ±2.3 μ²). There was no difference between males and females.
2) In all of the offspring of males and females which had both diabetes for 7 days (4 cases), 14 days (6 cases) or 22 days (4 cases), the number and the area of β- or α-cells were normal.
3) In all of the offspring of rats, diabetic for over 40 days, the number of β-cells was marked by decreased (46.6-50.4, average 48.4±1.2), and the area of β-cell was reduced (average 107.2±1.9μ²). The number of α-cells showed a slight decrease (average 13.8 ± 0.6), and the area of α-cell showed a slight reduction (average 57.2 ± 1.6μ²).
4) The number of β-cells in 3 of the 7 offspring of rats, diabetic for 23 days, was normal, and in the other 4 it was decreased (57.4-61.6, average 59.9 ± 1.6). The amount of decrease was half that seen in the offspring of rats with diabetes for over 40 days. The area of β-cell showed a slight reduction (average 108.7 ± 1.3μ²). The number and the area of α-cells were normal.
5) The number of β-cells in the 5 offspring of rats with diabetes for 24 days was decreased, in 2 to an average of 50.5, which is as low as in the offspring of rats with diabetes for over 40 days, and in 3 to an average of 58.4, of which the amount of decrease was half of that seen in the off-spring of rats with diabetes for over 40 days. The area of β-cell was slightly reduced (average 108.3 ± 1.2μ²). The number of α-cells was normal in some and somewhat decreased in others (average 13.4). The area of α-cell was reduced a little (average 58.6 ± 2.0μ²).
6) The number of β-cells in all of the offspring of rats with diabetes for 27 days, was decreased (46.3-51.8, average 49.5 ± 2.2) to the same degree as in rats with diabetes for over 40 days. The area of β-cell was reduced (average 106.8 ± 2.4μ²). The number of α-cells showed a slight decrease (average 13.7 ± 0.63), and the area of α-cell was also slightly reduced (average 56.8 ± 1.472).
7) These findings indicate that a period of at least 23 days of diabetes in both male and female rats is necessary to bring about disorders in the development of β-cells in Langerhans' islets in some of their offspring ; more than 24 days of diabetes is necessary to cause some disorder in the whole litter,

View full abstract