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Volume 22, Issue 3
Displaying 1-9 of 9 articles from this issue
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Michimaro Amano1979 Volume 22 Issue 3 Pages 425-433
Published: March 30, 1979
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSStudies were undertaken to clarify the action of L-Asparaginase (L-ASP) on insulin release from isolated islets of rats.
Adult rats were pretreated with 2, 000 U/kg of L-ASP at 6, 24, or 48 hr before isolation of the islets. The insulin release caused by glucose stimulation increased significantly in the islets of 6-and 24-hr rats, being approximately 1.4 to 1.7 times that at 120 min of incubation.
The insulin content of the islets increased significantly from 6 to 48 hr after the L-ASP treatment.
The insulin-releasing ratio of the islets (released IRI/islet IRI) did not change in the 6-and 24-hr groups, but decreased in the 48-hr group.
In vitro studies revealed only a slight decrease in insulin release (27.9±2.7 μU/islet/30 min) in the presence of medium containing 25 U/m/ of L-ASP. A significant decrease in insulin release was observed in the presence of medium containing 50 U/m/ of L-ASP (18.9±3.4 μU/islet/30 min), when compared to the values in control rats (34.3±8.8 μU/islet/30 min), by stimulation with 300 mg/d/ of glucose.
On the basis of these results, it is suggested that L-ASP may induce inhibition of insulin secretion in rat pancreatic islets by a mechanism different from that of cytotoxic agents such as streptozotocin and alloxan.View full abstractDownload PDF (1733K) -
Tadasumi Nakano, Hideki Ito, Hajime Orimo, Akio Noma1979 Volume 22 Issue 3 Pages 435-443
Published: March 30, 1979
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSIn order to elucidate the mechanism of hypertriglyceridemia in streptozotocin-induced (80 mg/kg, i.v.) diabetic rats, the total postheparin plasma triglyceride lipase activity (PHTGLA) was measured. Furthermore, selective measurement of PHTGLA was performed by preincubating postheparin plasma with protamine sulfate. The following results were obtained.
1) Plasma triglyceride, free fatty acid and total cholesterol levels were significantly higher inthe diabetic than in the control rats. Administration of insulin significantly decreased these parameters in the diabetic rats.
2) Total PHTGLA and protamine-inhibited PHTGLA were significantly lower in the diabetic than in the control rats. These changes were normalized by administration of insulin. Protamineresistant PHTGLA was not significantly different between the two groups.
3) Significant correlations between plasma glucose levels and triglyceride levels (r=0.76, p<0.001) and between plasma glucose levels and protamine-inhibited PHTGLA (r=-0.61, p<0.001) as well as total PHTGLA (r=-O.68, p<0.001) were observed.
These results suggest that the hypertriglyceridemia in the streptozotocin-induced diabetic rats was caused partially by decreased PHTGLA, mainly of extrahepatic origin, and that extrahepatic PHTGLA was regulated by insulin.View full abstractDownload PDF (2772K) -
2. Exocrine Insulin in Human SalivaKunihiro Doi, Akira Kawara, Masaaki Matsuura, Shigeki Fujii, Yasuaki Y ...1979 Volume 22 Issue 3 Pages 445-451
Published: March 30, 1979
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSIn addition to glucagon-like immunoreactive material, an immunoreactive insulin-like material (RI) has been found in extracts of salivary glands. This suggests that RI might be present in human saliva.
Sixteen normal controls, 10 chemical diabetics, and 30 overt diabetics were used for the presnt studies. Sera and saliva specimens were obtained before and during 50 g. oral glucose tolerance tests (OGTT) and arginine infusion tests (AIT).
OGTT: In all subjects, salivary immunoreactive insulin (IRI) rose later than serum IRI during OGTT. In normal and chemical diabetics, the mean peak levels of salivary IRI were lower than those of serum IRI. The mean fasting IRI in the saliva of normal subjects was 9 μU/m/ and the mean peak IRI was 32 μU/m/. On the other hand, in the diabetics, the mean peak level of salivary IRI did not differ from that of the serum. In all subjects, the levels of immunoreactive C-peptide in the saliva were very low.
AIT: During AIT, despite high levels of serum IRI, the salivary IRI showed little or no response to arginine in all subjects.
he dilution curve for salivary IRI was found to parallel the standard pork insulin dilutioncurve.
Gel filtration of human saliva or canine parotid gland in 3 M acetic acid on a Bio-Gel P-30 column (1.6 × 100 cm) revealed an IRI peak which eluted with a radioactive insulin marker.
The above observations indicate that (1) RI is present in saliva, (2) it is excreted on glucose stimulus, and (3) it is indistinguishable from and probably indentical to pancreatic insulin.View full abstractDownload PDF (984K) -
Kazuo Katsumata, Yoshinao Katsumata1979 Volume 22 Issue 3 Pages 453-459
Published: March 30, 1979
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSIt is well known that 100 mg % tolbutamide uncouples the oxidative phosphorylation of isolated rat liver mitochondria in vitro. However, this drug is considered to have little such effect in vivo, since a concentration of 100-150 mg % is apparently higher than the blood concentration of the drug attained after oral administration of the drug. We suspected that the uncoupling action of tolbutamide might be potentiated by the addition of fat-soluble substances which could influence the mitochondrial function, since tolbutamide is known to be a fat-soluble uncoupler. In the present study, we investigated the effects of palmitate and ethyl alcohol on the uncoupling action of tolbutamide on the oxidative phosphorylation of rat liver mitochondria in vitro. The respiration of the mitochondria was measured with an oxygen electrode and 10 mM sodium succinate was used as the substrate. It was found that ethyl alcohol potentiated the uncoupling action of tolbutamide more strongly than DMSO or NaOH. Ten mg % tolbutamide was capable of decreasing the ADP/O and respiratory control index (RCI) of mitochondria in the presence of both 0.1 mM palmitate and 0.4% ethyl alcohol. In the presence of both 0.8% alcohol and 0.1 mM palmitate, 30 mg tolbutamide decreased the RCI to 1 and ADP/0 to 0. Using an electron paramagnetic resonance technique, it has been reported that ethyl alcohol increases the fluidity of the mitochondrial membrane, and palmitate represents a well known uncoupler acting on the mitochondrial membrane. It was considered therefore that the uncoupling action of tolbutamide could be increased by ethyl alcohol and palmitate.
Since a small dose of tolbutamide such as 10-30 mg % is capable of causing some impairment of mitochondrial oxidative phosphorylation, tolbutamide is presumed to exert an influence on the mitochondrial oxidative phosphorylation of the liver in vivo.View full abstractDownload PDF (965K) -
Teiko Amemiya, Reiko Saito, Tadasu Kasahara, Yukimasa Hirata1979 Volume 22 Issue 3 Pages 461-470
Published: March 30, 1979
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSAlcoholic drinking, level of fasting serum triglyceride (TG) and sugar level (FBS) were assessed in 492 diabetic males in relation to differences in therapy, degree of obesity and diabetic conditions.
Higher TG levels were found in the group of drinking patients (drinkers) compared with patients who did not drink (non-drinkers). Especially significant differences were observed between drinkers (N=79, TG=228.7± 32.6 mg/dl) and non-drinkers (N=125, TG=131.7 ± 7.7 mg/dl) treated with sulfonylurea (SU)(p<0.001).
Higher TG levels were found in SU-treated patients less than 60 yr old whose condition was poorly controlled. These results suggest that alcohol potentiates an elevation of TG levels in patients with poorly-controlled diabetes who have been treated with SU.
There were no significant differences in FBS levels between drinkers and non-drinkers.
No significant differences were observed in levels of serum cholesterol (TC) among the patients grouped by types of therapy or between drinkers and non-drinkers.View full abstractDownload PDF (1342K) -
(Part 2) Clinical Evaluation of the Intravenous Administration of Tolbutamide in Normal, Hyperthyroid and Diabetic SubjectsNagao Heki, Hiroyuki Hosojima1979 Volume 22 Issue 3 Pages 471-477
Published: March 30, 1979
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSIn our previous report, a quantitative method based on GC-MS (gas chromatography-mass spectrometry) was described for the simultaneous analysis of tolbutamide and its metabolites from human plasma. We now report the plasm levels of tolbutamide (T) and two of its metabolites known to be formed in man i.e. the 1-p-hydroxymethylbenzensulfony1-3-butylurea (OHT) and 1-p-carboxypheny1-3-butylurea (COOHT) obtained by the mass fragmentographic method following intravenous administration of tolbutamide to normal, hyperthyroid and diabetic subjects. All three compounds are extracted from acidified plasma into ether and are converted to the corresponding N-1 methyl derivatives by reaction with diazomethane. The mode of action of the sulfonylureas as hypoglycemic agents is not yet fully clarified. However, they have been said in general to act by increasing the secretion of insulin from beta cells, although some workers believe that their effect is independent of insulin secretion. Explanation of the mode of action of the sulfonylureas is reviewed briefly, and studies on their action in groups of stable or unstable diabetics are reported. The following results were obtained. 1) Some dissociation was found between the hypoglycemic activity and insulin releasing ability of the three compounds. 2) A beta cell receptor site for tolbutamide exists which will also respond to hydroxymethyltolbutamide and, to a lesser extent, to carboxytolbutamide. 3) Tolbutamide, however, also acts on an extrapancreatic site and the hypoglycemia resulting from its administration is a summation of these two actions. Further studies are thus required to determine whether this represents a universal phenomenon. 4) Insulin release is not the only factor involved in the acute hypoglycemic action of sulfonylureas and indeed, may not even be the major factor.View full abstractDownload PDF (805K) -
Toshihiko Mihara, Yukimasa Hirata1979 Volume 22 Issue 3 Pages 479-484
Published: March 30, 1979
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSDiabetic neuropathy, retinopathy and nephropathy are representative diabetic complications. Even so, while one diabetic patient may display none of these complications, another may have them all since the pattern of diabetic complications in patients is so varied. This report concerns the classification of diabetic complications from the combination of neuropathy, retinopathy and nephropathy in 1191 diabetic patients who visited our diabetes center during the 12-month period from January through December, 1976. The classification of complications and their distribution were as follows: Type I (no complications), 17.8%; Type II (neuropathy only), 16.4%; Type III (neuropathy and retinopathy), 18.5%; Type IV (neuropathy, retinopathy and proteinuria), 15.7 %; Type V (proteinuria only), 9.5%; Type VI (neuropathy and proteinuria), 8.1%; Type VII (retinopathy only), 10.0%; and Type VIII (retinopathy and proteinuria), 4.0%. Diagnosis of neuropathy was based on diabetes-caused sensory disturbances or on diminished or lost knee jerk or Achilles jerk. Diagnosis of retinopathy was based on Ia and more advanced findings for Scott's classification. Diagnosis of nephropathy was based on proteinuria at examinaton.
In patients with a short duration of diabetes, Types I and II were common, whereas in patients with a long duration of diabetes, Types III and IV were increased. No significant relationships were apparent between sex, age at examination, fasting blood sugar level at first visit, and classification of diabetic complications. On the other hand, the frequency of hypertension was higher in Types IV and VIII than in the other types.View full abstractDownload PDF (944K) -
Takeshi Kobayashi, Kohei Yoshimitsu, Masao Kishitani, Noriomi Usukura, ...1979 Volume 22 Issue 3 Pages 485-493
Published: March 30, 1979
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSA possible link between viral infections such as mumps, Coxsackie B4 virus and congenital rubella and juvenile diabetes mellitus has been suggested. However, juvenile diabetes mellitus following acquired rubella infection has not been reported. A case of juvenile diabetes mellitus with myocarditis following rubella infection is reported. A 17-yr-old male patient whose father had suffered from diabetes mellitus, was admitted to Kanazawa University Hospital. He complained of weight loss (3 kg/2 months) and thirst, with accompanying hyperglycemia (fasting blood glucose level was 260 mg/100 ml), glycosuria and ketonuria, 2 months after rubella infection. Rubella infection was diagnosed from the typical skin rash, low grade fever and epidemic occurrence of similar symptoms among students at the Senior High School. It was confirmed by a rubella HI titer reduction from 562 to 256 in 4 months. On diet treatment alone, the ketonuria disappeared and urinary g lucose excretion decreased from 147 g/day to 2 g/day. Diurnal variations in blood glucoselevels, 50 g oral glucose tolerance test pattern and the responses of plasma C-peptide immunoreactivity to 100g glucose-glucagon-tolbutamide improved. The diabetic state of the patient was controlled by diet and 6 units of NPH insulin/day. Two weeks after admission, his ECG showed negative T waves in H, III and aVF, which were normalized in 6 months, suggesting viral myocarditis. It is conceivable that the diabetic state of the present patient was attributable to reversible insulitis following rubella infection.View full abstractDownload PDF (1313K) -
Junichi Yokoyama, Haruo Yamada, Naoko Tajima, Yoichi Sakamoto, Yoshio ...1979 Volume 22 Issue 3 Pages 495-499
Published: March 30, 1979
Released on J-STAGE: August 10, 2011
JOURNAL FREE ACCESSMeasurements of amylase activity and its isoenzyme pattern in the serum and urine were made in 53 cases of various diabetic type. The transition before and after treatment was investiga ted in some diabetics. The following results were obtained.
1) The serum amylase activity and its isoenzyme pattern were very similar between juvenile onset diabetes (JOD) and secondary diabetes mellitus due to chronic pancreatitis.
2) Pancreatic amylase in JOD was significantly lower than that in maturity onset diabetes (MOD)(p<0.O01).
3) The serum amylase activity was significantly increased after treatment of diabetes mellitus (p<0.001), but amylase clearance remained unchanged. The study on serum amylase isoenzyme indicated that pancreas-originating amylase was not increased in JOD, although both salivary and pancreas-originating amylase were increased in parallel in MOD.
4) In the case of diabetic ketoacidosis, the serum amylase activity was low before treatment. In some patients, the amylase activity was markedly raised during treatment with small intravenous insulin boluses. The increased amylase activity was due mainly to salivary type.
These results suggest that the production of amylase may be strongly dependent on the control of the diabetic state.View full abstractDownload PDF (462K)
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