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Volume 23, Issue 1
Displaying 1-10 of 10 articles from this issue
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Yasue Omori, Gaston Zahnd1980 Volume 23 Issue 1 Pages 1-9
Published: January 30, 1980
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSAlthough insulin degradation by insulin degrading enzymes in various tissues has been well studied, no report is yet available about insulin degradation by the rat pituitary.
Insulin degradation by the adenopituitary of male and female rats was observed using their hemipituitaries and homogenates. A medium containing 50μU/m/ or 25μU/m/ pork insulin was incubated with Krebs-Ringer bicarbonate buffer containing 2.5% BSA and 0.1% glucose.
The hemipituitaries were incubated in this medium and the IRI in the medium was measured before and after the incubation. Insulin degradation by the hemipituitaries increased in proportion to the incubation time. No degradation was observed on incubation at 4°C, but about 35% of the insulin in the medium was degraded with the hemipituitary during 60 min at 37°C. When the hemipituitary was heated for 10 min at 70°C before incubation, insulin degradation was apparently suppressed.
Comparisons were made on hemipituitaries of rats in the following groups; male and female rats fed and fasted for 48 hr, pregnant rats fed and fasted for 48 hr, and streptozotocine diabetic pregnant rats and streptozotocine diabetic non-pregnant rats. Insulin was degraded to the greatest degree (about 66%) by hemipituitaries of pregnant fed and fasted rats. Insulin degradation was more suppressed by hemipituitaries of rats in a fasting state than by those which had been fed.
The insulin degradation rate was lessened to the greatest degree (about 30%) in the case of hemipituitaries of streptozotocine diabetic non-pregnant rats.
The degradation of insulin in the hemipituitaries of male rats was less than that in female rats, although the difference was not significant.
The grade of insulin degradation in adenopituitary homogenates was intermediate between that of the liver and diaphragm muscle. Homogenates of these tissues showed a higher insulin degradation rate than the hemipituitary.View full abstractDownload PDF (2946K) -
[in Japanese]1980 Volume 23 Issue 1 Pages 11-21
Published: January 30, 1980
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSGlucose loading was carried out to study the metabolism of prostaglandin (PG) in patients with maturity-onset diabetics. Forty ml of 0.9% saline followed at 60 min later by 40 ml of glucose solution (glucose load), were given intravenously to normal individuals and diabetics. The effects on the plasma PG concentration and urine PG excretion rate were studied in 7 normal individuals and 24 diabetics, among which 7 were treated with anti-inflammatory drugs. The iPGE levels were significantly higher in diabetics than in normal individuals after the glucose load (p<0.05). The levels were higher in patients with fasting blood sugar levels in excess of 120 mg/dl than in those with levels below 120 mg/dl. Lower levels of blood glucose and plasma iPGE were always observed in diabetics treated with anti-inflammatory drugs than in those without. On the other hand, the urinary PGF1α excretion rate was significantly lower in diabetics than in normal individuals (p<0.025). These findings suggest that abnormal PG metabolism exists in diabetics.View full abstractDownload PDF (1704K) -
Masato Tominaga, Yoshihiro Ando, Hiroto Mashiba1980 Volume 23 Issue 1 Pages 23-28
Published: January 30, 1980
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSIt is impossible to measure insulin in the sera of insulin-treated patients by radioimmunoassay due to the presence of insulin antibodies in the sera. The same limitation appears to hold for enzyme immunoassay. However, the principle of the procedure in the Insulin Enzyme Immunoassay Kit (Mochida) is a sandwich method, although the radioimmunoassay depends on the competitive method. The binding capacity of insulin antibody in this enzyme immunoassay system thus appears to be still higher than that in the sera of insulin-treated patients. For this reason, the insulin antibodies in the sera of insulin-treated patients may be negligible compared to those in the assay system, and values obtained from the assay system for the sera of insulin-treated patients may be considered to express the total insulin values in the sera.
Measurements of insulin were carried out with this assay system for both sera and extracts of 18 insulin-treated subjects. Extraction of insulin was performed by the acid ethanol method. The values obtained for sera were compared with those for extracts, and were found to correspond closely. When the values for extracts were plotted on the X axis and those for sera on the Y axis, the following correlation between them was derived: Y=0.95X+ 42.12 (r= 0.951, p<0.001).
Fundamental examinations on the reproducibility, dilution test and recovery test, were performed with this assay system for sera containing insulin antibodies. The results were generally satisfactory.
It is concluded therefore that values obtained with this assay system for the sera of insulintreated patients, express the total serum insulin levels, even though insulin antibodies are present in the sera.View full abstractDownload PDF (707K) -
[in Japanese], [in Japanese], [in Japanese], [in Japanese]1980 Volume 23 Issue 1 Pages 29-38
Published: January 30, 1980
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSIn insulin-dependent diabetics, both the pancreatic A-cell response to hypoglycemia and B-cell response to hyperglycemia are markedly impaired. This suggests total destruction in the islets of Langerhans in such patients. If this is the case, an impaired response of human pancreatic polypeptide (HPP) producing cells (F-cells) to hypoglycemia might be expected.
Hyperglycemia followed by hypoglycemia was induced by successive intravenous administration of glucose (0.5 g/kg body weight) and MC-Actrapid insulin (0.2 U/kg body weight in controls; 0.2-0.4U/kg body weight in diabetics) at an interval of 30 min in 8 controls and 22 diabetics (12 insulin-independent and 10 insulin-dependent diabetics). The plasma concentration of HPP was measured by a radioimmunoassay established by us using the double antibody method.
In controls, the plasma level of HPP declined from a basal level of 54±17 (mean±SEM) pg/ml to a minimum of 34±5 pg/ml at 10 min after the glucose injection. In response to hypoglycemia (the minimum level of glucose was 25±2 mg/dl at 60 min), the HPP in controls increased steeply to a peak of 1, 320±200 pg/ml at 75 min, and then decreased gradually. In diabetics, the plasma concentration of HPP was suppressed to a level as low as in controls during the hyperglycemic stage. However, the response of HPP to hypoglycemia was significantly more impaired in insulin-dependent diabetics than in both the controls and insulin-independent diabetics, although there were no differences in the plasma glucose decrement, minimum level of glucose, or manifestation of hypoglycemic symptoms between these three groups. To estimate the real response of HPP to hypoglycemia, we introduced the index “HPP-area”, which is defined as the area under the curve for plasma HPP from the blood sampling time when the plasma glucose first fell to below 40 mg/dl to the time 30 min later. In insulin-dependent diabetics, the “HPP-area” was 7, 860±3, 040 pg·min/ml, which was significantly lower than both the 28, 490±4, 630 pg·min/ml in controls (p<0.005) and 21, 630±4, 720 pg·min/ml in insulin-independent diabteics (p<0.025).View full abstractDownload PDF (2629K) -
Y. Tasaka, S. Inoue, M. Takei, Y. Hirata1980 Volume 23 Issue 1 Pages 39-45
Published: January 30, 1980
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSIn the unstable type of diabetes, it has been reported that the secretion of insulin as judged from serum CPR determinations is characteristically low in both 100 g OGTT and arginine infusion tests. In order to study the relationship between the insulin and C-peptide contents diabetic pancreas and the stability of fasting blood sugar (FBS) levels before death, a diabetic pancreases were analysed for insulin and C-peptide by a gel filtration technique using acid alcohol extracts of pancreas. As the inbex of the degree of instability of the FBS levels, during 6 months prior to death was adopted. The results obtained may be summarized as follows.
1) The mean contents of diabetic pancreatic insulin and C-peptide were 0.72±0.21 U/g and 7.39±1.91 μg/g, respectively. These values were significantly low compared to those of nondiabetics.
2) In 6 well or fairly well controlled diabetics whose standard deviations for FBS were less than 59 mg/dl, the pancreatic insulin and C-peptide contents were 1.07±0.19 U/g and 10.90±1.12 μg/g, respectively.
3) In 3 unstable diabetics whose standard deviations for FBS exceeded 98 mg/dl, the contents of pancreatic insulin and C-peptide were very low (insulin content, 0.02±0 U/g, C-peptide content, 0.34±0.33μg/g).
4) In 3 unstable diabetics, the fasting CPR values were below the assay limit. These findings suggest that the main reason for instability of blood sugar levels in diabetes may be related to the devastation of pancreatic B cells.View full abstractDownload PDF (1050K) -
Motoaki Shichiri, Yoshimitsu Yamasaki, Ryuzo Kawamori, Toyohiko Morish ...1980 Volume 23 Issue 1 Pages 47-55
Published: January 30, 1980
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSAn artificial endocrine pancreas has been developed by combining a glucose infusion system with the artificial beta cell system. In this system, glucose was infused on the basis of the proportional and derivative actions to blood glucose concentration with a time delay constant. The glucose infusion algorithm so prepared was as follows:
G.I.R. (t) =Cp·BGp-BG (t-τ) +Cd·-ΔBG (t-τ)
where G. I. R. (mg/kg·min) represents the glucose infusion rate, BGp the projected value of the blood glucose concentration, ΔBG the rate of change in blood glucose concentration, Cp and Cd are coefficients for the proportional and derivative actions, and τ(min) is the time delay constant between blood withdrawal and the initiation of glucose infusion. Cp is calculated from the equation: Cp=GS/100·T, where GS is the glucose space per body weight (g/kg) and T is the time to be set for supply of the glucose deficient amount. In the present series of experiments, T was selected as either 10 or 4.
1) When glucose was infused on the basis of the proportional action with a 20-min time delay, the insulin-induced hypoglycemia in depancreatized dogs could be restored to normoglycemia in the same manner as seen in normal dogs.
2) A speedier and less fluctuating restoration to normoglycemia could be obtained when the glucose was infused on the basis of the proportional plus derivative action with a 4-min time delay.
These results indicate that the artificial endocrine pancreas so developed constitutes not only a useful device, for the safety control of blood glucose, but also an elegant research tool for analyzing the blood glucose regulatory mechanism.View full abstractDownload PDF (2186K) -
Akihiro Funakoshi, Tetsuro Sakimoto, Etsuo Yuno, Hiromasa Amagase, Ken ...1980 Volume 23 Issue 1 Pages 57-64
Published: January 30, 1980
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSTwo cases of hypoglycemia due to hepatocellular carcinoma are reported. The first was a 55-yr-old woman who was admitted to Kyushu University Hospital in February 1975, due to episodes of unconsciousness. Her blood sugar level at the time of attack was 25 mg/dl, and the level of serum AFP was high (26.5 mg/dl). Autopsy revealed hepatocellular carcinoma, without cirrhosis, and the liver tumor weighed 2040g. There were wide peritoneal disseminated metastases which weighed about 3kg. The levels of serum IRI and CPR were within normal limits, and serum ILA was undetectable. Overconsumption of blood glucose by the tumor tissue thus appeared to represent one of the most probable mechanisms for the hypoglycemia observed in the present case.
The second case was a 52-yr-old man who was admitted in May 1976, due to obstructive jaundice. His blood sugar level was 16 mg/dl at the time of an hypoglycemic attack after admission. The level of serum AFP was 12 mg/dl. Autopsy revealed hepatocellular carcinoma with cirrhosis, and no apparent metastasis. The weight of the liver tumor was 2780g. The levels of serum IRI and CPR were low, but the levels of ILA in acid-ethanol extracts of the tumor tissue and serum were high. High density encapsulated granules were revealed in the tumor tissue by electron microscopic examinations. The possibility of hypoglycemia resulting from increasing levels of ILA in the tumor tissue. was therefore suspected.
On reviewing 83 cases of hypoglycemia due to hepatocellular carcinoma which were reported in Japan from 1936 to 1976, a high incidence in 40-to 50-yr-old men was observed. Many cases had accompanying cirrhosis of the liver, and large tumors weighing on average 3942g (1590-8200g). Increasing levels of glycogen granules in the tumor cells were noted with interest.View full abstractDownload PDF (2901K) -
Katsuhito Ogawa, Nobuo Matsui, Takeharu Itatsu, Haruo Hirayama, Kozo S ...1980 Volume 23 Issue 1 Pages 65-73
Published: January 30, 1980
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSA case of insulin autoimmune syndrome accompanied by hyperthyroidism is reported here.
The patient was a 43-yr-old woman diagnosed as having hyperthyroidism in 1971, and treated with methimazole for 60 days in 1976. She had never received insulin injections previously.
In August 1977, she was admitted due to hypoglycemic attacks. On admission, a 100g o-GTT revealed a diabetic tolerance curve. Her serum immunoreactive insulin (IRI) and C-peptide reactivity (CPR) showed extremely high levels such as 11, 600 μU/m/ and 19.5 ng/mi, respectively. Serum T3 and T4 showed thyrotoxic levels and autoantibodies to thyroid microsomes were positive. Anti-insulin antibodies in the IgG fraction were detected by gel filtration and radioimmunoelectrophoresis, and the light chain of the antibodies was predominantly of the kappa type. The percent 125I-insulin binding as an index of the antibody titer determined by the ethanol-precipitation method was significantly higher (64.4%) than in a control (12.6%), and a large amount of IRI (4, 980μU/ml) could be extracted from the serum obtained on the day of hypoglycemic attack.
The patient had frequently suffered from hypoglycemic attacks, from which she was thereafter relieved spontaneously coincident with a remarkable decrease in IRI and CPR.
One year later, when the hyperthyroidism was controlled with propylthiouracil, a glucose tolerance test revealed a borderline glucose curve. An insulin tolerance test (0.15 U/kg I. V.) showed high sensitivity to exogenous insulin (hypoglycemia at 35 min) and normal responses of serum cortisol, h-GH and plasma glucagon with a decrease in CPR of 38% of the initial value. On the other hand, antithyroid and anti-insulin antibody titers remained elevated, suggesting that the autoimmunity of the two diseases had continued during this time.
The pathogenesis of the insulin autoimmune syndrome in relation to hyperthyroidism is discussed.View full abstractDownload PDF (2111K) -
Hisako Fushimi, Sukenori Tsukuda, Toshiaki Hanafusa, Mitsuo Nishikawa1980 Volume 23 Issue 1 Pages 75-82
Published: January 30, 1980
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSA case of insulin autoimmune syndrome with insulinoma and active rheumatoid arthritis is reported. This 56-yr-old housewife was admitted due to recent hypoglycemic attacks. The patient, with Whipple tcias, had been treated for chronic active rheumatoid arthritis with occasional steroid injections into the joints for 6 yr prior to admission. One hundred grams OGTT was diabetic. The fasting IRI determined by the the double antibody method was 120-900 μU/ml. Insulinbinding antibody was found by the ethanol precipitation method, dextran charcoal method and separax electrophoresis. Both the levels of insulin-binding antibody (0.39 mU/ml) and total extractable IRI of the serum (557μU/ml) were markedly high. The light chain of antibody type was kappa and lambda. Tumor staining was recognized in the body of the pancreas, and pancreatectomy was performed leaving the pancreas head. Every 1 cm slice of the resected pancreas was studied histologically and two small adenomas were found. Gomori's trichrome or aldehyde fuchsin staining revealed that the tumors were consisted mainly of B cells. Over 1, 000 cases of insulinomas and 19 cases of insulin autoimmune syndrome have been reported previously but no combinations were noted. The present case of insulin autoimmune syndrome is thus interesting since it developed during the course of active rheumatoid arthritis and was associated with insulinomas.View full abstractDownload PDF (4400K) -
Hikaru Fujii, Akira Kawa, Yasuko Kono, Takami Matsuyama, Haruto Ohe, N ...1980 Volume 23 Issue 1 Pages 83-86
Published: January 30, 1980
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSThe present study was undertaken to evaluate the possible roles of suppressor T cells in the pathogenesis of juvenileonset and insulin-dependent diabetes mellitus (JOD). The numbers of subjects examined were as follows: 32 healthy controls, 19 JOD patients, 14 MOD patients and 14 insulindependent diabetes with late onset (IDD).
IgG FcR-positive T cells (TγA cells) were detected by the method of Nibo et al. The percentage of TγA cells was 8.1±1.6%(mean±SD) in the healthy controls. The percentage of T-A cells in the JOD patients was significantly low compared to those in the healthy controls, MOD patients, and IDD patients. There was no difference in FBS levels between the JOD and IDD patients. IDD patients received daily injections of insulin. It seems unlikely therefore that the decrease in TγA in the JOD patients was related to the levels of FBS or injection of insulin.
The relationship between the above results and possible autoimmune mechanism in the pathogenesis of JOD is briefly discussed.View full abstractDownload PDF (490K)
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