Folia Endocrinologica Japonica
Online ISSN : 2186-506X
Print ISSN : 0029-0661
ISSN-L : 0029-0661
Volume 37, Issue 8
Displaying 1-4 of 4 articles from this issue
  • 1961 Volume 37 Issue 8 Pages 807-848
    Published: November 20, 1961
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
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  • Yasumasa ISHIKAWA
    1961 Volume 37 Issue 8 Pages 849-868_6,803
    Published: November 20, 1961
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
    Experimental studies were made on the changes of blood sugar value of alloxan diabetes rabbits during a peroid of one month, after performing pancreas resection of 30%, 60% and 80% excision of body and tail of the organ respectively. And further histological examinations were conducted on the remaining pancreas and the other endocrine organs.
    The hyperglycemia of alloxan diabetes recoverd to normal value about 48 hours after a 30% excision of pancreas, and the blood sugar contents were kept to normal value for the following 2 weeks. At the end of the 2nd week, it indicated a slight elevation but after 5 days it returned back to normal value.
    In the 60% and 80% excised cases, the high blood sugar value was kept for 3 weeks after the operation, and then gradually went down to normal value.
    On the other hand, the results of histological examination of several endocrine glands, demonstrated active regeneration of B cells in the remaining pancreas of the 30% excised cases. It was observed that the regeneration of B cells in the 60% and 80% excises cases was half as compared to the 30% excised case.
    In the same pictures, hypofunction was observed in pituitary glands, adrenal glands, and thyroid glands, but no changes in ovaries and testicles.
    From the above mentioned results, the regeneration of B cells in the remaining pancreas, and the hypofunction of the pituitary glands, adrenal glands, and thyroid glands, which was brought about by the resection of pancreas, are considered as a means of recovery of blood sugar contents of alloxan diabetes to normal value. These results suggest the possibility of surgical treatment of diabetes in clinical cases.
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  • Takesi OHNO
    1961 Volume 37 Issue 8 Pages 869-895,803
    Published: November 20, 1961
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
    The exact mechanism of therapeutic effect of antidiabetic sulfonylurea has been a disputed subject.
    The author has attempted to clarify the situation by means of in vitro and in vivo experiments.
    For in vitro experiments, Wistar strain of rats were used, while for in vivo experiments, dogs were used.
    As sulfonylurea products, IBTD, BZ55 and B860 were employed, though for later experiments D860 was used exclusively. For the experimental technique in vitro, the diaphragm and liver slices of normal and alloxan diabetic rats were incubated with Warburg's apparatus.
    The sulfonylurea was added to the incubation medium but it was also administered to the rat prior to excision of tissues. In vivo experiments, insulin-like activity (after Shimazu's method) and glucagon-like activity (after Shinko's method) of blood were examined with simultaneous foollow-ups of arterial and venous blood sugar levels.
    The drug was injected intravenously in the carotid or portal vein. In one type of experiment, the injection was made into the arteria pancreaticoduodenale.
    In the latter case, endocrine activity of pancreas was determined with blood drawn from the vena pancreaticus.
    The results are summarized as follows :
    1) In vitro experiments with the diaphragm, a marked inhibition of glycogenolysis and output of glucose were observed in the incubation medium, containing 10μg/ml D860. With Krebs-Ringer-glucose medium glucose uptake and glycogen synthesis showed a 30 per cent increase.
    2) With the liver slices, a similar phenomenon was observed within 10 to 100μg/ml concentration of sulfonylurea. D860 was most effective and IBTD with concentration of 10 to 100μgml also showed strong inhibition of glycogenolysis. With Buchanan-Hastings-Nesbett solution, the author observed acceleration of glucose uptake and glucogensynthesis with sulfonyl-urea concentration of 10μg/ml.
    3) Sulfonylurea in concentration over 300μg/dl caused increased glycogenolysis and glucose output of the diaphragm and liver slices, particularly of the latter.
    4) Experiments with the liver slices under glycogenetic conditions, i.e. Buchanan-Hastings-Nesbett solution with 1000mg/dl glucose showed no apparent change in glycogen synthesis but in the environment without glucose D860 showed inhibition of glycogenolysis, thus indicating the glycostatic effect.
    5) Investigation of insulin-like activity and glucagon-like activity of blood drawn from the vena pancreaticus revealed a pattern of response upon injection of D860, which was quite similar to that observed following glucose injection, i.e. there was an increase of insulin-like activity 2-3 hours after injection of glucose or D860.
    6) From the investigations above mentioned the author reached the conclusion, that sulfonyl-urea exerts it's first phase effect through the accelerated consumption of endogenous insulin thus inviting initial hypoglycemia and initial decrease of insulin-like activity of plasma. The second phase effect observed, was the increase of insulin secretion, inhibition of glucose output from liver, increase of glucose uptake in the peripheral tissues and consequent retardation of restoration of hypoglycemic blood sugar level.
    7) The present day concepts upon the mechanism of antidiabetic sulfonylurea was discussed from the results of our own experiments and references.
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  • Toshihiko HASHIMOTO
    1961 Volume 37 Issue 8 Pages 896-906,804
    Published: November 20, 1961
    Released on J-STAGE: September 24, 2012
    JOURNAL FREE ACCESS
    The role of glucagon in carbohydrate metabolism seems to be better understood nowadays. But since there is no reliable bioassay method for the estimation of glucagon-like activity (Abbr. as glucagon activity) in blood, no detailed studies on the role of glucagon in the carbohydrate metabolism could be carried out.
    In our clinic, a new bioassay method of blood glucagon activity was developed by Shinko, basing the glucagon activity on the liver slices.
    By using this method, the author tried to analyse the physiologic role of blood glucagon.
    The results are summarized as follows :
    (A) Studies with in vitro technique.
    Wistar strain rats were used, weighing 100-120gm. They were fed for 3 to 5 days with a carbo-hydrate rich diet and then made to fast for 48 hours. This experimental condition was necessary to standardize the glycogen content of the rat liver. Liver slices were taken and then incubated in Warburg's apparatus. As incubation medium, modified Buchanan-Hasting's Solution with 1000mg./dl. glucose, was used. Novo-semilente insulin or Glucagon-Lilly was added to the medium in various concentrations. Δ-glucose in the medium and Δ-glycogen of the liver were examined and these values were observed.
    The values are summarized as follows ;
    (1) Increasing doses of insulin added to incubation medium usually increase Δ-glycogen and glucose uptake
    (2) When glucagon was added to the Insulin free (incubation) medium, in which liver slices were incubated, no particular change of glucose uptake was observed with low concentration of glucagon. If the doses of glucagon is elevated to 1μg./ml. or more it causes only a slight decrease of glucose uptake and Δ-glycogen.
    (3) When insulin was added to the medium, which contained 10-4μg./ml. of glucagon, glucose uptake from the medium increased but this increase of glucose uptake was lower than that in the experiment, in which no glucagon was added to the medium. Δ-glycogen of the liver slices decreases under insulin addition. These results indicate the possible co-action of glucagon and insulin in some instances.
    (4) When insulin was added to an incubation medium, of which glucagon concentration was 10-2μg./ml., there was an increase of glucose uptake under insulin action. On the other hand, action of glucagon is potentiated by insulin and this leads to increased glycogenolysis. These two reactions act antagonistically to each other, the result of which is expressed as a mild fluctuation of glucose uptake.
    (5) When insulin is added to a medium, which contains glucagon to 1μg/.ml. or 10μg./ml. concentration, a progressive glycogenolytic action of glucagon is observed with the addition of increasing doses of insulin.
    (6) Glycogenolytic effect of added glucagon on the liver glycogen was detectable for about 30 minutes in case of simple glucagon action. In 120 minutes, glycogenolitic effect of added glucagon is over and there is an enhanced glucose uptake from the medium as compared with liver slices incubated in simple Buchanan-glucose medium.
    Thus glucagon effect is suppressed by coexisting insulin in the first phase of time, but on the whole, this glucagon effect has a tendency to remain active for a long time.
    Glycogenolytic effect of epinephrine and glucagon on the liver slices was compared in a medium, to which 1 u./ml. insulin was added. In the first phase of epinephrine action, slight glycogenolysis was seen but in the course of 120 minutes, the glycogenolytic effect of epinephrine was over and even the glucose uptake from the medium was observed. In the same kind of experiment where glucagon was used instead of epinephrine, there was an enhancement of glycogenolysis. These results point to quite a different mode of action of glucagon and epinephrine.
    (B) Experiments in vivo
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