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Biomedical subjects

T Toyota

Publications and source records attributed to T Toyota.

At least 379 records · Page 21Linked to original sources

The endocrine pancreas in pyridoxine deficient rats.

Because the supplementation of pyridoxine (vitamin B6) improves the glucose tolerance in gestational diabetes and adult onset diabetes, pyridoxine deficiency has been considered to be one of the factors that cause diabetes mellitus. We produced pyridoxine deficient rats by giving pyridoxine-free food with deoxypyridoxine which competitively the activity of pyridoxal phosphate. In these pyridoxine deficient rats plasma insulin during the glucose tolerance test was significantly low as compared with controls. In vitro experiments of pancreas perfusion showed that secretion of insulin and glucagon was impaired in the pyridoxine deficiency. Since the restriction of diet-calorie caused a decrease in arginine-induced secretion of insulin and glucagon from the isolated pancreas, the impairment of the endocrine pancreas may depend on malnutrition. Pyridoxine deficiency is surely one of the factors that impair the endocrine pancreas by multifactorial derangement of metabolism besides the tryptophan-nicotinic acid pathway.

Animals↗

Stimulatory effect of secretin on pancreatic polypeptide in diabetic patients.

In diabetic patients plasma levels of pancreatic polypeptide (PP) increased four fold after intramuscular injection of secretin (50 CHRU, Eisai Co.) in spite of the lack of response of plasma insulin, plasma glucagon and blood glucose levels. In control subjects, PP levels did not change significantly after secretin injection. Since pancreatic polypeptide has is known to have an inhibitory effect on the exocrine pancreas, the present study suggests the possibility that disturbed function of the exocrine pancreas in diabetic patients could be related to the remarkable response of PP to secretin-stimulation.

Adult↗

Effects of islet-activating protein (IAP) on blood glucose and plasma insulin in healthy volunteers (phase 1 studies).

Islet-activating protein (IAP) is a new active substance purified from the culture medium of Bordetella pertussis. The active protein possesses a molecular weight of 77,000 and an isoelectric point of pH 7.8. The nature of IAP-action is characterized by enhancement of insulin secretory response to glucose and other stimulants. A single injection of IAP into spontaneous diabetes rats resulted in normalization of their glucose intolerance over a period of a month. Acute and chronic animal toxicity tests showed that LD50 of IAP was 127 micrograms/kg in mice and 144 micrograms/kg in rats. After these animal experiments, phase 1 studies were designed and undertaken to establish dosage, duration of action and other factors. IAP of 0.5 micrograms/kg or 1.0 micrograms/kg did not bring about any serious toxic or adverse effects in five volunteers. On the 4th day of a single injection of IAP, insulin secretory response was proved to be enhanced. Follow-up studies showed that the IAP-action continued over a month or at most two months. Two features of IAP, i.e., the enhancement of insulin secretory response and the long duration of the action, was confirmed in healthy persons as well as in animals. As expected, IAP has a strong antigenic reaction resulting in formation of IgG antibody and possibly IgE antibody. The antigenicity of IAP causes some hindrance to clinical usefulness. For avoidance of anaphylactic reaction, IAP should be given repeatedly with care. The problem concerning antigen-antibody reaction should be overcome as soon as possible before the clinical use of IAP as a medicament.

Adult↗

HLA antigens in juvenile onset diabetes.

To study association between juvenile onset diabetes (JOD) and major histocompatibility gene complex, 40 patients with childhood onset diabetes and 120 healthy subjects were typed for HLA. Bw54 was present in 33 percent of the patients with JOD, while it appeared in 8 percent of the controls. Expressed as a relative risk, the antigen Bw54 confers a susceptibility to the development of JOD which is 5.3 times that in the controls. JOD shows a little high degree of association with A9 (78%). However, the A9-antigen is common in the Japanese and appears in 58 percent. Though less striking, the decreased frequency of B12 was 3 percent of JOD, less than 15 percent of the controls (p less than 0.05). There was no association between Bw54 and JOD with family history of diabetes.

Adolescent↗

Islet activating protein (IAP) derived from the culture supernatant fluid of Bordetella pertussis: effect on spontaneous diabetic rats.

The early phase of insulin secretion to an oral glucose load was blunted in spontaneous diabetic rats. The blunted insulin secretion was associated with markedly impaired glucose tolerance. A single injection of the islet activating protein (IAP), a protein derived from the culture medium of Bordetella pertussis, into the spontaneous diabetic rats normalised glucose tolerance. The increase in insulin response to glucose was an important contributing factor to the improvement of glucose tolerance. This curative effect of the IAP on the diabetic state was of long duration; glucose tolerance remained virtually normal over a period of one month in the diabetic rats. Perfusion of the isolated pancreas of the diabetic rats pretreated with IAP showed an increase in insulin response to glucose and loss of suppression of glucagon secretion by noradrenaline.

Animals↗

Effects of hexapeptide, a compound analogous to insulin B chain fragment B-21-26(DP-432) on the glucose uptake into the perfused hind limb of rats.

DP-432 is a synthetic new peptide analogous to insulin B-chain fragment B21-26. It has been reported that this hexapeptide shows insulin potentiating action besides insulin-like activities in adipose tissue and diaphragm of rats. The perfusion of the hind limb of rats was performed according to the procedure of Ruderman with some modifications. The medium was Krebs-Ringer bicarbonate buffer containing 0.5% bovine albumin and 8.3 mM glucose. The erythrocytes were omitted from the medium. In this experimental procedure it was shown that the glucose uptake into the hind limb of rats increased by infusion of DP-432 (100 microgram/ml). The amount of glucose uptake into the hind limb responded to insulin doses (50, 100, 1000 muU/ml). DP-432 had insulin-like activity of 100 muU/ml. However, DP-432 itself did not have any potentiation of insulin activity on the muscle.

Animals↗

Activities of hepatic enzymes in spontaneous diabetes rats produced by selective breeding of normal Wistar rats.

Acitivites of the hepatic enzymes were determined in spontaneous diabetes rats. The activities of the enzymes were compared with those in normal rats and in streptozotocin diabetic rats. In the spontaneous diabetes rats, glycogen phosphorylase and glycogen synthase were 14.6 +/- 0.6 and 1.73 +/- 0.15 U respectively. The activities of both the enzymes were significantly increased. In the spontaneous diabetes rats glucokinase was 3.82 +/- 0.5 U showing a significant increase. On the contrary, the activity of the enzyme was decreased in the streptozotocin diabetic rats. Glucose-6-phosphatase was increased both in the spontaneous diabetes rats and in the streptozotocin diabetic rats. Fructose-1,6-diphosphatase was increased in the spontaneous diabetes rats. Glucose-6-phosphate dehydrogenase was increased in the spontaneous diabetes rats and decreased in the streptozotocin diabetic rats. In the spontaneous diabetes rats phosphofructokinase showed a reduction of the activity and glucose-6-phosphate dehydrogenase was elevated. These findings are consistent with the results of activities of the hepatic enzymes in adult-onset diabetic patients. These patterns of the hepatic enzymes in the spontaneous diabetes rats were different from those in the streptozotocin diabetic rats. From these patterns of activities of the hepatic enzymes, the spontaneous diabetes rats produced by repetition of selective breeding according to Goto et al. (1975,1976) are an excellent model of human adult-onset diabetes.

Animals↗

Oral administration of chymotrypsin labile peptide for a new test of exocrine pancreatic function (PET) in comparison and pancreozymin-secretin test.

A new test using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (N-BT-PABA) for an evaluation of exocrine pancreatic function was compared with a pancreozymin-secretin test in 38 subjects. Urinary recovery of PABA, which is absorbed from the intestine and conjugated in the liver after an oral administration of N-BT-PABA, depends mainly on chymotrypsin activity. The recovery rate of PABA in urine decreases in chronic pancreatitis, in which chymotrypsin activity in the duodenal juice is disturbed. The recovery rate of PABA in calcifying chronic pancreatitis was 40.2 +/- 15% and significantly less than 81.2 +/- 7.4% in normal subjects (P less than 0.01). The amount of PABA in urine during eight hours was correlated with parameters of volume output- bicarbonate concentration and amylase output stimulated by injections of pancreozymin and secretin (P-S test). The new test using N-BT-PABA is useful for the evaluation of exocrine pancreatic function in general practice.

4-Aminobenzoic Acid↗

Plasma C-peptide response to oral glucose in low insulin responders, subdiabetic, and diabetic subjects.

It is one of the characteristic features in diabetes mellitus that insulin response to glucose is low. Nine low insulin responders with normal glucose tolerance in whom prediabetes mellitus should be suspected were found to be included in 104 apparently healthy subjects (9%). A 100 g glucose tolerance test (GTT) was performed in nine apparently healthy subjects with a low insulin response and 11 healthy subjects with a normal insulin response. A 50 g GTT was performed in 15 normal subjects, 20 subdiabetics, 38 chemical diabetics and 17 mild diabetics. In all subjects C-peptide during GTT was estimated by the double antibody systems using a synthetic human C-peptide. Though C-peptide secretion from the beta cell of the pancreas seems to keep pace with insulin secretion, the peak of C-peptide was delayed in its appearance in the circulating blood, as compared with that of insulin. The pattern of plasma C-peptide during GTT in diabetics was identical with that of insulin. In the low insulin responders C-peptide response to glucose was observed to be lower like that of insulin than in the normal insulin responders. However, a molar ratio of C-peptide to insulin at 30 min during GTT in the former was higher than that in the latter.

C-Peptide↗

Insulin and growth hormone secretion stimulated by intravenous administration of arginine in the low insulin responders (prediabetes?).

Twelve apparently healthy subjects who showed a low insulin response to glucose were selected from two different age groups, 6 from youngers aged 19 to 22 and 6 from olders above 65 years old, and responses of insulin and growth hormone secretion to an intravenous administration of arginine were investigated. Incidence of low insulin responders, who showed the peak value of plasma insulin during GTT below 45 muU/ml, was 9% among the young subjects and 24% among the old ones. Insulin secretion stimulated by arginine in 6 young low responders was not different from that in the control group matched with regard to age and body weight, and the values of growth hormone during arginine infusion were higher than those of the control group. In the old low insulin responders, insulin secretion stimulated by arginine was significantly lower than that in the control group, but the growth hormone secretion was not different from that in control. The present study showed that insulin and growth hormone secretion stimulated by arginine in young low-insulin-responders were different from those in the old ones. The low insulin responders are discussed in regard to prediabetes.

Adult↗