The problem as to what is stained by the beta granule stainings seems to be one of the most important problems to be elucidated in the field of pancreatic islet at the level of light microscopy. The two main stainings, aldehyde fuchsin (AF) and pseudoisocyanin (PIC) were thus analysed with special reference to the relation of stained substance to insulin.
First experiment. Adult guinea pigs (unfed for 24 hrs) were given an intraperitoneal injection of glucose (2g/kg) and killed every hour until 6 hrs after that. The histological sections of the pancreas revealed that most of AF stained as well as PIC metachromatic granules in the B cells which filled the cytoplasm in the control animals disappeared in 2 hrs after glucose administration. A bio-assay of the insulin content of the same pancreases indicated that 50% of insulin had been lost from the pancreas of the 2 hr cases.
Second experiment. Adult rabbits (unfed for 24 hrs) received an intravenous injection of alloxan (200 mg/kg) and were killed at various time lapses, mainly 30 min and 24 hrs after the injection. The B cell granules as stained by AF and PIC did not, until 24 hrs, show any decrease in their amount within the cell and in their stainability, although conspicuous damages of the B cell were recognized already 30 min after alloxan treatment. A bio-assay study on each of the animals revealed a 26% and 40% decrease in insulin content of the pancreas in the 30 min and 24 hr cases respectively. As some islets were found to survive under the effect of alloxan, it is supposed that the insulin in the alloxanized pancreas may be gathered in those islets; the insulin content in the damaged islets may thus be lower than indicated by the above figures. This suggestion is supported by that the zinc content (dithizon staining) of the damaged islet, especially in 24 hr cases, is extremly low whereas it is at a considerable level in the surviving islets.
The first experiment of glucose administration indicates that the distribution of the substance demonstrated by AF and PIC well reflect the dynamics of insulin whereas the second with alloxan treatment shows that the amount of the stained element may by far deviate from that of insulin within the cell.
What is then the substance shown by these so to called insulin stainings? It moves and is released together with insulin in the normally functioning B cell as shown in the case of glucose administration. It is, however, left in the cell when insulin is lost from it by an acute cell damage as in the case of alloxan intoxication. A reference to the electron microscopic findings suggests that an element fulfilling this condition may be the membrane sac of the beta granules. The fact that the AF positive and PIC metachromatic substance is not recognized in the pancreas fixed either in ethanol or in aceton may suggest that it would contain lipid.
Although PIC is generally believed to be a special dye causing metachromatic reaction of B cell granules, the present study revealed that more routine basic dyes such as toluidin blue cause a weak metachromasia which is conspicuously intensified when the sections are previously oxidized with KMnO₄.
In the present communication, a consideration was also made on the above mentioned early decrease in the insulin content of the pancreas in alloxan treatment. The blood glucose level (by glucose oxidase method) showed a sharp drop two to five min after the injection. This initial hypoglycemea which continues only one min well corresponds to that of the early decrease in the insulin content of the alloxanized pancreas and suggests that a considerable amount of insulin may be released as early as a few minutes after the alloxan administration.

View full abstract

As to the fine structure of the pancreatic islets, numerous papers have been published. However, there are still some unsolved problems concerning the production and extrusion mechanisms of the secretory granules of islet cells.
In this sudy, the fine structural changes of islet cells especially insulinsecreting B-cells were observed under some experimental conditions such as the artificial hibernation of bats, Myotis lucifugus lucifgus, and administrations of alloxan, pilocarpine and dehydroascorbic acid (DHA) to dogs. Some other animals including the monkey, guinea pig, dove and snake were also used to study nervous elements in the pancreatic islets.
The islets of the bat contain A, B, C. D, and W-cells. The glucagon-secreting A-cells are a few in number and characterized by containing phloxine-staind red granules by light microscopy. These granules are electron dense spherical ones enveloped with a smooth membrane as observed by electron microscopy. The B-cells secreting insulin, which are numerous in number, are characterized by thioninestained blue secretory granules. These granules are amorphous masses or crystalloids enveloped by a smooth membrane, when observed with the electron microscope. The C-cells are rare and possess the clear cytoplasm without any granules, while D-cells which are also few in number, contain some ghostlike granules. Scarcely occurring W-cells are characterized by electron dense granules, which are similar in morphology to the A-cell granules, and contain a filamentous whorl.
The pancreas of bast and monkeys contained ganglion cells in the interlobular connective tissue or between acinar cells. The nerve endings within the pancreatic islets could be divided into two types : 1) Type 1 contained agranular synaptic vesicles (500 Å in diameter) along with a few large cored vesicles (1,000 Å), and were thought to be the cholinergic (parasympathetic). 2) Type 2 was characterized by containing vesicles of the same size as those of agranular synaptic vesicles, but a majority of these vesicles contained electron dense cores. These endings also contained a few large cored vesicles, and might be the adrenergic (sympathetic). In the pancreatic islet of the monkey, bat, guinea pig and dove, the nerve endings frequently occurred and loosely contacted with the islet cells, but in the case of the snake pancreatic islets, there were no such nerve endings.
By the artificial hibernation the pancreatic islets of bats morphologically changed as follows : 1) Islet cells diminished their volumes and contained the dark cytoplasm and pyknotic niclei. 2) Most of the secretory granules in the B-cell changed into bar-shaped granules which might contain more concentrated insulin, as compared with those of amorphous granules. These alterations of islet cells gradually recovered to normal condition by 24 hours by the refeeding.
The dog pancreas usually has A, B and D-cells. The B-cell contained bar-shaped secretory granules, while the A-cell contained electron dense round granules.
After the administration of alloxan, the B-cells changed remarkably as follows : Most bar-shaped granules became low in density or empty 4.5-6 hours after the injection of alloxan. This might suggest the increased release of insulin via diacrine secretion mechanism. The B-cell contained enlarged endoplasmic reticulum and sometimes possessed an area of the hydropic degeneration which was characterized by containing some amorphous masses. In some cases, the B-cells were severely destructed, containing some autophagic vacuoles with a large number of secretory granules. Some B-cells contained a well developed Golgi apparatus containing some immature granules. These cells also contained parallel-arranged endoplasmic reticulum.
Most B-cells were destructed 24 hours after alloxan treatment and the islets were composed of a large number of A-cells.
After the administration of pilocarpine or DHA,

View full abstract

The mechanism of insulin synthesis and release from pancreatic beta cells was investigated in rabbits. Islets of Langerhans were observed by light and electron microscopy. Serum insulin levels and extractable insulin content of pancreas were measured by dextran coated charcoal immunoassay.
Results a) Rabbits being starved for 10 days : Blood sugar levels and serum immunoreactive insulin (IRI) showed the decreasing tendency during starvation. Extractable insulin from pancreas gradually fell toward a half of pre-starved levels on the 10th day. On the same day of starvation, beta cell nuclei became smaller and beta granules almost disappeared in aldehyde thionin staining. In electron microscopy, striking characteristic of these beta cells was the appearane of a large number of empty sacs almost same sized as limiting membranes of beta granules. Golgi complex was lacking in dilatation and vacuolation of its membranes and premature granules were absent.
b) Rabbits injected intramuscularly with lente insulin of 2U/kg for 3 months : Remarkable degranulation of beta cells in light microscopy, and constriction of Golgi complexes accompanying with disappearance of premature granules, appearance of a large number of empty sacs with significant decrease of beta granules in electron microscopy, were observed.
c) Rabbits administered with glycodiazin at a dose of 100mg/kg/day for 2-9 months : Maximal rise in serum IRI levels was observed within 3 months and then gradual decrease continued until 9th month. Extractable insulin from pancreas decreased to about a half of the levels prior to administration. In electron microscopy, significant decline of beta granules were recognized but accumulation of empty sacs in cytoplasm were not observed. Golgi complexes were more extensive, showed a higher incidence of dilatation of their lammelle and a larger number of premature granules.
d) Rabbits fed with high carbohydrate diet for 3 days or droppingwise injected with 10% glucose solution for 6-8 hours both after 10 days starvation : Regranulation of beta cells in light microscopy, reappearance of cored beta granules, prominent endoplasmic reticulum and well developed Golgi complexes accompanying with many premature granules in electron microscopy were observed in the pancreatic islets of high carbohydrate diet feeding rabbits. But the pancreatic beta cells from glucose injected animals after starvation did not show any reactivation by glucose injection.
Summary and Conclusion
The data are summarized as follows. The lack of insulin demand such as starvation or insulin administration bring on the significant decline in insulin synthesis despite the slow releas of insulin from beta cells. On the other hand, glycodiazin administration or high carbohydrate diet feeding after starvation accelerate both synthesis and release of insulin in beta cells. On the basis of these findings, the following hypothesis about insulin secretion is proposed. Insulin or insulin precursor synthesized at the site of endoplasmic reticulum might be condensed to mature beta granules through the form of premature granules in close connection with Golgi complexes. Responding to insulin demand, beta granules would become soluble and oozeout into the cell sap through the limiting membranes of granules. Insulin excluded in cytoplasm might be released into capillary (diacrine type of secretion, not emiocytosis). Then limiting membranes of granules would remain in cytoplasm as empty sacs. They would be utilized rapidly for insulin synthesis in active beta cells, but in inactive beta cells they would remain longer in cytoplasm.

View full abstract

Insulinoma, as a typical case of hyperinsulinism, has engendered interest in mechanism and regulation of insulin release. In two patients with insulinoma, plasma insulin responses after administration of various insulin releasers and inhibitors were studied. Ultrastructure of beta cells in tumors were also observed electronmicroscopically.
In both cases, the fasting insulin levels in plasma were greater than that observed in any other normal subjects. Excessive rises of plasma insulin were found after administration of glucose orally, and of glucose or glucagon intravenously. The rise of insulin level during glucose loading was depressed completely by pulse administration of epinephrine, and propanolol, a beta receptor blocking agent, while not during glucagon loading. The plasma insulin levels in both cases were consistenly high during intravenous administration of glucose for five hours. Under the condition studied here, it seems likely that insulinoma, as a benign tumor, has no automatism in insulin release, but has more exaggerated insulin level in plasma than normal control.
Electronmicroscopically, it was shown that in insulinoma β-granules of β-cells were generally scanty. With a little variation, the cores of granules were generally round, while there were mixed forms in normal ones; being round, rectangle and triangle.
The cell organella such as endoplasmic reticulum, Golgi apparatus ribosome seemed more prominent, indicating an increased protein synthesis.
These findings would suggest that in insulinoma, the major part of insulin synthetized in β-cells can be secreted to the blood stream without being stored as β-granules.

View full abstract

In this experiment the mechanism involved in the phenomenon of hypoglycemia induced by the administration of sulfonylurea, and by the administration of leucine in leucine sensitive cases was studied by using sulfonylurea, 1-leucine, and α-ketocarboxylic acids in vivo and in vitro.
1. Sulfonylurea, which has a hypoglycemic effect, is coordinated to zinc ions in vitro and forms an insoluable complex. In an experiment in vivo using ³⁵S-Rastinon, results of autoradiography indicate the complex-formation of sulfonylurea and zinc ions in islets of pancreas. These results suggest, that the release of insulin from islets induced by the disintegration of three dimensional structured complex of zinc ions and insulin in B cells into two dimensional or lineal structured form. It is induced by the chelating of zinc ions with sulfonylurea. Namely, the block of biological activity of stainable zinc in B cells by administered sulfonylurea causes the disintegration of zinc-insulin complex and facilitates the release of insulin from islets.
2. On the basis of results of morphological studies on the pancreas in 2 cases of infantile leucin sensitive hypoglycemia and on insuloma in 3 cases with the leucine sensitivity, it was concluded that, although the normal B cells of islets contain a large quantity of stainable zinc, the insulin producing cells in leucine sensitive cases contain a very small quantity of stainable zinc. And this is one and the only common finding through all cases. It is speculated, that in leucine sensitive cases these small quantities of zinc ions combine with S atoms of S-S bond of insulin, because these S atoms have severaly two electron lone pairs, and the coordinate bond of zinc ions and S atoms is stronger than that of zinc ions and amino acid. Therefore in leucine sensitive cases, zinc ions and insulin barely form the three dimensional structured complex. 1-leucine disintegrates easily into a-ketoisocaproic acid by existence of zinc ions. Therefore the administered leucine cannot remain intact in islets; and a-ketoisocaproic acid (a metobolite of leucine) or its metabolite, reacts in islets. Although the essential amino acids (except leucine) cannot decompose the three dimensional structured complex of zinc-insulin, α-ketoisocaproic acid can decompose the complex. Results of an experiment in vitro support the above mentioned speculation. Namely, the white precipitate, which was deposited by adding an aqueous solution containing zinc chloride into the standard insulin solution, was dissolved by adding an aqueous solution of α-ketoisocaproic acid. Results of an optical rotatory examination in this experiment system also support this specutaion. The same fact occurred in an experiment of α-ketobutyric acid system.
3. Based on this speculation on the mechanism of leucine sensitivity, the hypoglycemic effect of α-ketobutyric acid was studied in leucine sensitive cases. α-ketobutyric acid shows a hypoglycemic effect in cases with leucine sensitivity of human and rat, and this effect is caused by the stimulation of insulin-release from islet induced by the administration of this substance.
From results of these experiments, it is concluded that the release of insulin from islets is strongly influenced by the stainable zinc in B cells. These zinc ions form the three dimensional structured complex with insulin, and the decomposure of this complex induced by the chelating of zinc ions facilitates the release of insulin from islets.
For revealing leucine sensitivity, it may be a very important factor that the quantity of stainable zinc in insulin producing cells is very small, and based upon this factor the mechanism of sensitivity to leucine was discussed.

View full abstract

Since more knowledge indispensable to determine whether the lesion is in the hypothalamo-pituitary axis or in the gonads in management of ovulatory defects in the human, a new test for the purpose of examining the LH-releasing function of pituitary was devised and its clinical significance was evaluated.
20 mg. of conjugated estrogen (Premarin) was injected into 51 patients suffering from various types of ovrian insufficiency : 11 cases of occasional anovulatory cycle (O.A.C.), 11 cases of persistent anovulatory cycle (P.A.C.), 18 cases of amenorrhea 1st grade (Am. I) and 11 cases of amenorrhea 2nd grade (Am. II).
Urine specimens were collected just before the injection, 2 and 4 hours, 4 and 7 days after that. Each specimen was concentrated by the modified method reported by Wide et al. (1962), LH like substance was measured immunologically using with advantage the cross-reaction of LH with HCG.
Fifty three tests have been performed up to the date of Feb. 29 1968 (2 patients were tested twice, and the same results were obtained). Various patterns of LH excretion were obtained; however, they might be classified into 5 types (type I to type V).
Some correlations were observed between the patterns of LH excretion and the clinical types of ovarian insufficiency : 7 out of 11 cases of O.A.C. showed pattern I, the rest of them showed type II. i, e, no types of III-V were observed in the group with anovulatory cycles. Patterns of type III were only seen in the group of Am. I., and type IV were only in Am. II. While 5 out of 7 cases with type V were in Am. II, 2 of them were in Am. I.
Fourteen out of 51 cases were laparotomized and wedge resections of ovaries were performed. Ovaries were examined grossly and histologically. Eight out of 10 cases of anovulatory cycles or Am.I showed type I, the other 2 cases showed type III (Case 3 of O.A.C. who showed type III was tested at the period of Am. I), the cases of Am. II. showed type IV or V. In all patients who showed type I the polystic ovaries were observed more or less in grade, and in 8 of 10, spontaneous ovulatory cycles were obtained following the wedgresection. However, in 4 cases of Am.II. atrophic, hypolastic or dysgenetic ovaries were seen and no ovulations were obtained after the operation.
From these results the following speculations can be mentioned :
Type I. Comparatively high level in normal range of LH and polycystic ovaries were observed in this group. In the patients of this type LH releasing function in hypothalamopituitary axis is slightly disturbed (hyper function), but the main factor for the ovulatory defects is in the ovary.
Type II. Since no case of this type was laprotomized, it is quite difficult to interpret.It might be speculated, however, that this type indicates hypogonadotrophic hypogonadism caused by slightly disturbed LH releasing function which is able to react to the positive feed-back of estrogen promptly.
Type III. This type is often seen in the group of Am. I and well reacts to the gonadotropic therapy, moderately disturbed hypogonadotropic hypogonadism, i, e, moderate pituitary insufficiency is suspected.
Type IV. Customarily used hypergonadotropic hypogonadism, that originates in such intrinsic gonadal failure as gonadal dysgenesis, menopause or the like, is presumed.
Type V. This type suggests so-called hypogonadotropic hypogonadism caused by intrinsic pituitary or hypohtalamic failure such as panhypopituitarism, etc.
Applying this test, ovarian dysfunction which has been traditionally summarized as hypogonadotrophic or hyper-gonadotrophic hypogonadism can be classified or diagnosed more in detail. Furthermore, it might be mentioned that this test is useful in the diagnosis for the polycystic ovary syndrome.

View full abstract

It has not yet been confirmed whether pituitary synthesis of ACTH is actually accelerated under conditions of acute stimuli, or not.
In order to clarify this problem, adenohypophysial RNA, which seems to reflect the intensity of protein synthetic activity, plasma ACTH activity and plasma corticosterone were simultaneously determined after various acute stimuli in rats.
Adenohypophysial RNA was determined by Schmidt-Thaunhauser-Schneider's method based on the spectrophotometric measurement of liberated pentose by orcinol reaction.
Plasma ACTH activity was measured by an in Vitro bioassay using beef adrenocortical slices which was developed in our clinic.
DeMoor's fluorophotometric method was employed for measurement of plasma corticosterone.
The results were summarized as follows :
1). Adenohypophysial RNA content in female rat was slightly higher than in male, but this difference was not statistically significant, : the value was 5.26±0.23 μg/mg of tissue and 4.39±0.18 pg/mg in male, respectively.
2). Plasma ACTH activity reached to the highest level at 5min. after ether-vapour exposure and thereafter declined to control level, but plasma corticosterone reached its highest level at 30 min. after ether. Adenohypophysial RNA content increased significantly at 60 and 120 min. after ether-exposure, their value before the ether and at 60 and 120 min.after were 4.68μg/mg, 6.24μg/mg (P<0.01) and 7.17μg/mg (P<0.02), respectively.
3). Pituitary RNA, plasma ACTH activity and plasma corticosterone were determined at intervals of 2.5 to 120 min. following laparotomy. Plasma ACTH began to increase at 2.5 min. following incision and continued to stay on its high level up to 120 min.
Adenohypophysial RNA did not increase rapidly after laparotomy, but it increased significantly at 60 and 120 min. following incision. Pituitary RNA content before incision, at 2.5, 60 and 120 min. after incision were 4.29μg/mg, 5.68μg/mg (n.s.), 7.15μg/mg (P<0.01) and 5.80μg/mg (P<0.05), respectively.
4). The changes of adenohypophysial RNA content, plasma ACTH activity and plasma corticosterone were observed at intervals of 2.5 to 60 min. following intra-venous administration of Lysine-8-Vasopression (100mU/100gm) into tail vein. Plasma ACTH activity was significantly increased at 2.5 min. after injection, but 15 min. later it returned to control level.
Changes of adenohypophysial RNA following L-8-V administration were not so re-markable as compared with changes following ether or laparotomy as above mentioned. Actual adenohypophysial RNA content before L-8-V injection, at 2.5 and 60 min. after injection were 3.75μg/mg, 4.55μg/mg (n.s.), and 5.22μg/mg (P<0.5), respectively.
5). The effect of intermittent bell-ringing continued for 30 min. on adenohypophysial RNA, plasma ACTH activity and plasma corticosterone was investigated. All of these indices were significantly increased after bell-ringing. RNA content changed from 4.69μ/mg of control value to 6.13μg/mg (P<0.05) after bell-ringing.
6). As summary, following conclusion could be drawn. Various kinds of stimuli applicated in this report seems to mobilize the endogenous hypothalamic CRF (Corticotrophin Releasing Factor).
The next response is the rapid increase of plasma ACTH activity within 2.5 to 5.0 min., which is to be correlated to the release of ACTH from pituitary, for extended periods of certain time interval.
The increase of adenohypophysial RNA, which is postulated as to reflect the increase of ACTH synthesis, appeared relatively in later period as compared with the increase of plasma ACTH.

View full abstract

Studies on glucose-6-phosphatase (G6Pase) have been so far mainly confined to the one found in liver and no detailed research was ever performed on the similar enzyme in kidney. In the present work, existence of a specific G6Pase in rat kidney with the properties and activity level similar to those of the liver enzyme is confirmed from the results of comparative studies on some foundamental properties of such phosphatases as reported below.

View full abstract

Variation of glucose-6-phosphatase (G6Pase) activity in rat liver and kidney under thyroidal dysfunctioning was investigated on the groups of experimental animals treated as follows :
a) Potassium iodide administration; 10γ per day for a week b) 3, 3', 5'-Triiodothyronine administration; 5γ per day for a week c) L-Thyroxine administration; 30γ per day for a week d) Mercazole administration; 10 mg per day for a week e) Thyroidectomy; more than 4/5 of the thyroid gland removed f) Thyroxine administration (30γ per day for a week) after thyroidectomy

View full abstract

A case of goiter proved to show impaired iodine organification and iodotyrosine coupling is presented.
A 24 year-old housewife was admitted to the hospital because of swelling of the anterior neck. She had been well until 6 months prior to the admission, when she noted swelling of the anterior neck without any symptoms suggestive of thyroid disfunction. She had had no treatment for this and found that the swelling had been growing. There was no family history of goiter. Physical examination disclosed a well developed female with normal body proportions and no hearing loss. The thyroid gland was diffusely enlarged (Grade 3). There was no stigmata suggestive of thyroid dysfunction. Laboratory tests including liver function tests, renal function tests, serum electrolytes and serum protein fractionation were within normal limits. BMR was -7% and +15%, PBI was 4.7 μg/dl and 5.4 μg/dl and ¹³¹I-T₃ Resin Sponge uptake test was 28.9% and 32.0%. Thyroid up-take of ¹³¹I was high, showing 40% at 3 hr., and 80% at 24 hr., after oral administration of isotope tracer.
Following the administration of potassium thiocyanate, marked discharge of the radioiodine which was once transported into the thyroid occurred. Thyroidal ¹³¹I, which was calculated 40% at 3 hr., after ¹³¹I administration, decreased to 19% at 30 min. and 9% at 60 min., after thiocyanate administration. Thyroidal ¹³¹I uptake test and the discharge test with thiocyanate were investigated in other members of her family and failed to show high uptake or discharge phenomenon of radioiodine.
A part of the thyroid gland was removed seven days after radioiodine injection. Histological study revealed Struma colloides macrofollicularis. There was no sign of chronic inflammation. After a part of the thyroid tissue was homogenized and was hydrolysed with trypsin and pancreatin in Krebs Ringer phosphate buffer (pH 7.4), paperchromatographic analysis of the tissue was performed by the ascending system in butanol acetic acid solvent. Iodoaminoacid fractions were calculated from the radioactivities on the chormatogram. The fractions of inorganic iodide, monoiodotyrosine (MIT), diiodotyrosine (DIT) and thyronine (T₄+ T₃) were calculated 16.4%, 44.8%, 32.8% and 2.2%, respectively. It was demonstrated that there was an increase in MIT/DIT ratio (1.36) and a decrease in T₄ + T₃fraction.
The results may suggest a partial defect of the process of thyroidal iodide organification and iodotyrosine coupling as a cause of the goiter.

View full abstract

Recently, steroidhormones are used for the treatment of various diseases in large doses and for a long period.
The problem of suppression of adrenocortical function in these cases required increasing attention to it as an iatrogenic disorder.
Investigation of the mechanism of adrenocortical suppression under the long term steroid treatment was contemplated with the expectation that this study will be beneficial to devise the clinical methods of prevention of adrenocortical suppression in these clinical cases.

View full abstract

Altogether, 60 patients were selected for the comparative studies on the clinical effectiveness following SU preparations or biguanide (abb. BG) therapy and the clinical results were compared with each other.
Out of 60 patients, 34 hospitalized patients were almost severe diabetics (except SU true resistant, insulin dependent diabetics) and the remaining were mild or moderate diabetic outpatients of our hospital.
Attempts were made to be able to select those types fit for the BG therapy under a thorough study of the clinical characteristics manifested by those BG-good responders.
The degree of responsiveness to SU or BG was evaluated from the reduction of blood sugar levels, viz. the fasting and postprandial blood sugar levels (abb. FBS and PPBS), and the urine sugar value within a given time due to SU or BG treatment.
In all the patients, who were treated with SU or BG separately (some cases with both combined) from 2 to 3 months, levels of sugar in the blood (both FBS and PPBS) weekly, and urine sugar daily were determined, in outpatients were measured postprandial urine sugar.
The practical evaluations of the therapeutic effects finally were compared with the mean of those values in blood and urine after each therapy.
On the other hand, there are some groups of patients who show not so infrequently the complaints of gastric troubles by those given BGs. Therefore, in order to decide this question of complaints the gastric juices of those who complained and those who did not complain, were tested. The BG preparations used were chiefly “Phenphormin”, sometimes “Silubin”.
The results and certain comments are summarized below.
1. BG preparations were more effective in nearly half of the 60 patients on the evaluation of blood and urine glucose value within a given time due to SU or BGs therapy.
2. On the three components of evaluation, in general, the PPBS and the urine sugar levels were favorable among those who responded well to the BGs, and FBS levels were favorable to SU-good responders.
3. Half of the BG-good responders included those poor responders to insulin but all of them were better responders to the SU, compared with insulin.
4. Out of 15 BG-good responders, on whom the insulin sensitivity test was performed, roughly half of them showed abnormal sensitivity.
5. High thresholds of the urine sugar excretion were seen comparatively in a large number of the BG-good responders.
6. Complaints of gastric troubles were made not infrequently by those given the BGs. The gastric juices of those who complained were found to.be nonacidic.
7. The above clinical investigations provide a guide for the applicability of the BGs, according to the types of diabetes.
To sum it up, one is inclined to assume the presence of more or less extra-pancreatic factor or factors in those BG-applicable cases.

View full abstract