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Biomedical subjects

Y Shigeta

Publications and source records attributed to Y Shigeta.

At least 217 records · Page 12Linked to original sources

Focal hyperplasia of intracytoplasmic filaments in the canine parathyroid gland treated with nalidixic acid.

Focal hyperplasia of intracytoplasmic filaments of 100A in diameter was observed within chief cells of the parathyroid gland in dogs treated with nalidixic acid. The structure, as a rule, was located in the neighborhood of the nucleus and no other cell organelles were detected within it. Its size had a wide spectrum from a small part of the cytoplasm to as large as half a cell. Golgi apparatus and rough endoplasmic reticulum in the involved cells had a tendency to atrophy. These cells occasionally contained less secretory granules. Lipid droplets are diffusely increased. The pathogenesis and significance of the present intracytoplasmic filaments remain to be determined. However, as lipid deposition, atrophy of Golgi apparatus, poorly developed rough endoplasmic reticulum occur in a hypofunctional or degenerative state, it might be possible that filamentous hyperplasia is closely associated with that state.

Animals↗

Hypokalemia and sodium retention in patients with diabetes and chronic hepatitis receiving insulin and glycyrrhizin.

Of 9 patients with chronic hepatitis treated with intravenous administration of 40 to 200 mg/day of glycyrrhizin, 3 diabetic patients receiving concomitant insulin developed hypokalemia, sodium retention and suppression of both plasma aldosterone concentration and plasma renin activity after the administration for 3 to 6 days. In the remaining 6 patients (5 nondiabetic and 1 diabetic) receiving no insulin, the administration over the long term (18 to 266 days) never caused these abnormalities. The development of hypokalemia and sodium retention in the patients was not associated with increased urinary excretion of potassium, indicating a different condition from pseudoaldosteronism caused by the desoxycorticosterone-like action of glycyrrhizin. These findings suggest that insulin which is known to have hypokalemic, antinatriuretic and antikaliuretic activity, as well as glycyrrhizin plays an important pathogenetic role in the observed electrolyte disturbance, and suppression of both renin and aldosterone.

Adult↗

Evidence of the lack of receptor-mediated insulin degradation in human cultured lymphocytes (RPMI-1788 line).

We studied insulin degradation in human cultured lymphocytes (RPMI-1788 line) with a small but significant number of lysosomes under the electron microscope. Insulin degradation determined by the TCA solubility method was 64.6 +/- 1.2% (mean +/- SEM) at a trace concentration after the incubation with 2.0 x 10(7) cells (4.0 x 10(7) cells/ml) for 60 min at 37 degrees C. Because insulin degradation was 54.6 +/- 7.0% in the cell-free buffer in which 2.0 x 10(7) cells were previously incubated, most of the insulin was degraded outside of the cells. Gel filtration of the radioactive materials also revealed that most of the labeled insulin in the medium was degraded, and the main peak of the cell-associated radioactivities was intact labeled insulin. Chloroquine, a lysosomotropic agent, failed not only to increase insulin binding but also to decrease the insulin degradation. Other lysosomal protease inhibitors, antipain and leupeptin had also no effect on insulin degradation. In contrast, bacitracin (500 micrograms/ml) significantly decreased the insulin degradation analyzed by TCA solubility, receptor-rebinding, and the gel filtration method. These results suggest that insulin molecules are degraded by the enzymes leaked from the cells. The non-receptor mediated process, which is the bacitracin sensitive pathway, might be a general mechanism of insulin degradation in human cultured lymphocytes in vitro.

Bacitracin↗

A community study of diabetes in a population with a high diabetes mortality rate.

Among the 47 prefectures of Japan, the prefecture of Shiga stands out due to its remarkably high death rate from diabetes, especially in female diabetics. In an attempt to clarify the causes, a diabetes detection study was carried out in the inhabitants aged 40 or over of five communities. The prevalence rate of diabetes was 1.7%; male 2.5% and female 1.3%. However, the study could include only 14% of the inhabitants (3253 out of 23,249 inhabitants). In a community named Aito, where the diabetic death rate was the highest among communities of the prefecture and the study covered 95% of the 1849 inhabitants, the prevalence of diabetes was 3.0% in males and 1.2% in females (2.2% in total). Obesity, hypertension and ischemic change in electrocardiogram were more frequent in female diabetics than in male diabetics in this community. These results suggest that the high death rate from diabetes in the female population is not caused by a high prevalence rate of diabetes and female diabetics may be affected by several risk factors which influence their prognosis more often than that of male diabetics.

Adult↗

Acceleration of ethanol metabolism by administration of uridine diphosphate(UDP) in rat.

To see if UDP accelerates the metabolism of ethanol, Wistar female rats were given UDP(100 mg/kg b.w.) intra-gastrically prior to a single dose of ethanol (3 g/kg b.w.) ingestion. UDP pretreatment accelerated blood ethanol disappearance rate by 50% (mg/kg animal/hr) by Widmark formula. Increases of the hepatic triglyceride concentration 6 hours and 20 hours after ethanol administration were significantly low in UDP pretreated animals suggesting the lipotropic effect of UDP. Neither the activity of alcohol dehydrogenase nor microsomal ethanol oxidizing system was affected by UDP pretreatment. The ratio of lactate to pyruvate in liver 6 hours after ethanol was not changed as compared with that of the control whether the rats were pretreated with UDP or not. There were significant increases in hepatic ATP content and the size of the adenylate pool in UDP pretreated group, whereas the energy charge was unchanged as compared with ethanol-alone group. These data suggest that UDP enhances ethanol metabolism possibly by causing a change in ATP metabolism.

Adenosine Triphosphate↗

Characterization of [LeuB-24]- and [LeuB-25]-insulin analogues. Receptor binding and biological activity.

Human [LeuB-24]- and [LeuB-25]-insulins were semi-synthesized from porcine insulin by an enzyme-assisted coupling method. The receptor-binding ability of [LeuB-24]- and [LeuB-25]-insulins was 30--48% and 2--5% respectively of that of human insulin. There was no significant difference in degradation between human insulin and these analogues on incubation with isolated adipocytes. The decreased affinity of these analogues was due to an increased dissociation rate rather than a change in the association rate of their binding to human cultured lymphocytes. The negative co-operative effect of [LeuB-24]- and [LeuB-25]-insulin was decreased to 50 and 1% respectively of that of human insulin at a concentration of 100 ng/ml. The ability of [LeuB-24]- and [LeuB-25]-insulin to stimulate 2-deoxyglucose uptake in isolated rat adipocytes was 35 and 4% respectively of that of human insulin. These analogues did not have an antagonistic effect on the biological activity of human insulin. The immunoreactivity of [LeuB-25]insulin was similar to that of porcine or human insulin, whereas [LeuB-24]insulin demonstrated decreased binding to anti-(porcine insulin) antibodies. These findings suggest that B-chain phenylalanine-25 residue is more crucial for receptor binding and negative co-operativity, whereas the B-chain phenylalanine-24 residue may play a more important role in binding to anti-insulin antibody.

Adipose Tissue↗

Effect of L-dopa administration on insulin binding: possible role of growth hormone in regulation of insulin receptor affinity.

We have investigated changes in insulin binding to erythrocytes in response to the oral administration of 500 mg of L-Dopa in ten healthy subjects. L-Dopa administration increases insulin binding from 5.18 +/- 0.14% (mean +/- SEM) to 6.18 +/- 0.34% (P less than 0.05) with concomitant increase in basal plasma growth hormone from 1.3 +/- 0.1 ng/ml to 14.4 +/- 4.8 ng/ml (P less than 0.05). The increase in insulin binding is due to increase in affinity of insulin receptor without changes in the number of insulin receptors. The plasma insulin and glucose did not show significant changes after L-Dopa administration. Direct incubation of L-Dopa with erythrocytes did not affect insulin binding to the cells. These results suggest that growth hormone may directly or indirectly induce acute alteration in affinity of insulin receptors on erythrocytes.

Adult↗

Light and electron microscopic changes of the exocrine pancreas in diabetic dogs induced by streptozotocin.

Light and electron microscopic studies on exocrine pancreas of diabetic dogs with duration of diabetes up to a year induced by streptozotocin were performed. In the pancreatic acinar cells of the long-term diabetic dogs, atrophy, hyperplastic nodules, and interacinar and interlobular fibrosis were exclusively observed by light microscopy and autophagic vacuoles, lipid droplets, fragmentation of rough endoplasmic reticulum, and decrease or varying size of zymogen granules were much more frequently found by electron microscopy compared with the control. The results might indicate the possibility that insulinopenia causes the injurious effect on exocrine pancreas to produce interacinar fibrosis.

Animals↗

Effect of acute exercise on insulin binding to erythrocytes in type II diabetes.

We studied the effect of acute short-term exercise on insulin binding to erythrocytes in plasma with non-insulin dependent diabetes mellitus and normal controls. In the normal controls, insulin binding was increased immediately after the exercise and returned to the basal level at 30 min after the exercise. This increase was due to an affinity change without any change in the insulin receptor number. In contrast, insulin binding tended to decrease in the diabetics after the exercise, and this change was due to a decreased affinity without any change in the number of insulin receptors. These results indicate that the control mechanism of insulin receptor affinity in response to exercise is different in non-insulin dependent diabetics and normals.

Adult↗

Semisynthesis and biological properties of the [B24-leucine]-, [B25-leucine[- and [B24-leucine, B25-leucine]-analogues of human insulin.

Trypsin-catalyzed coupling of porcine desoctapeptide-insulin with synthetic octapeptides produced the [LeuB24]- (I), [LeuB25]- (II) and [LeuB24, LeuB25]- (III)analogues of human insulin. I, II and III displayed respectively 20--30%, 1--2% and 0.5% of the receptor binding activity of the normal hormone. Biological activities of these analogues seemed to be proportional to their binding potencies when assayed in vitro, while in an in vivo assay analogue I was fully active and II exhibited 10--20% of normal activity. III was less active than II in all assays tested.

Adipose Tissue↗