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Biomedical subjects

Y Shigeta

Publications and source records attributed to Y Shigeta.

At least 145 records · Page 8Linked to original sources
PubMed1989

[A new treatment of hyperkalemia in renal failure with selective beta 2-adrenergic stimulant, terbutaline sulfate].

Plasma potassium lowering effect of a selective beta-2 adrenergic stimulant, terbutaline sulfate (TRB) was investigated in fourteen patients with chronic renal failure (CRF) receiving maintenance hemodialysis. Fourteen CRF patients with chronic glomerulonephritis (CGN) (5 male, 2 female) and diabetes mellitus (DM) (3 male, 4 female) were infused with 0.4 mg TRB dissolved in 100 ml of 10% maltose solution. Serum potassium level in the CGN group significantly (p less than 0.01) decreased after 20 minutes infusion and maximum lowering effect (1.1 mEq/l) was obtained 40 minutes after the start. On the other hand, the maximum lowering effect of serum potassium level in the DM group (0.77 mEq/l) was obtained 60 minutes after the start. No serious metabolic and hemodynamic side effect was observed except only slight transient tachycardia in 2 CGN patients and 3 DM patients. Thus, a beta-2 selective adrenergic stimulant, terbutaline sulfate may be useful for acute treatment of hyperkalemia in CRF patients by way of the stimulation of potassium uptake in the cells.

Adult↗
PubMed1988

Insulin resistance by unprocessed insulin proreceptors point mutation at the cleavage site.

Failure to cleave the interconnecting site between alpha- and beta-subunit produced insulin proreceptors in the plasma membranes which had markedly low affinity to insulin, leading to extreme insulin resistance in a patient. We performed cDNA sequence analysis of the cleavage site of the insulin proreceptor from the patient. Polymerase chain reaction was used to obtain large amount of cDNA coding for the region including the interconnecting site. A thermostable DNA polymerase, Taq polymerase, successfully produced enough amount of cDNA of the region to be sequenced. The results showed AGG (Arg) to AGT (Ser) point mutation, resulting in the change of interconnecting sequence of the two subunits from -Arg-Lys-Arg-Arg- to -Arg-Lys-Arg-Ser-. These results suggest that the tertial structure change of the cleavage site leads to production of unprocessed insulin proreceptors.

Base Sequence↗
PubMed1988

A new prostaglandin E1 analogue (TFC-612) prevents a decrease in motor nerve conduction velocity in streptozocin-diabetic rats.

A new prostaglandin E1 analogue (TFC-612) was orally given to streptozocin-diabetic rats for 4 weeks after the induction of diabetes and its effects on motor nerve conduction velocity were studied. The compound significantly prevented a decrease of the velocity but did not reverse abnormal sorbitol and myo-inositol contents of the sciatic nerve. The results suggest that TFC-612 has a potent effect on diabetic nerve dysfunction via other mechanism than the correction of sorbitol and myo-inositol metabolisms and could be a potential compound for therapy of diabetic polyneuropathy.

Alprostadil↗
PubMed1988

Alcohol-induced enhancement of intestinal gamma-glutamyl transpeptidase activity in rats and humans: a possible role in increased serum gamma-glutamyl transpeptidase activity in alcoholics.

It is a well-known phenomenon that serum gamma-glutamyltranspeptidase (gamma-GTP, EC 2.3.2.2.) activity is increased after chronic consumption of ethanol, and gamma-GTP has been, therefore, widely used as a sensitive marker for detection of alcoholism and its related liver disease. However, the precise mechanisms whereby the chronic ethanol consumption leads to an increase in serum gamma-GTP activity are not fully understood. In the present study, we investigated the relationship between the intestinal and serum gamma-GTP activities after chronic ethanol consumption both in rats and humans. Chronic ethanol feeding to rats resulted in a significant increase in serum gamma-GTP activity associated with a significant increment of the intestinal gamma-GTP activity. The histochemical staining of gamma-GTP in the mucosa of the small intestine of these animals demonstrated enhanced gamma-GTP activity at the microvilli of the brush border membrane, lamina propria of the mucosa, and endoplasmic reticulum of the intestinal epithelial cell. The augmented activity in the lamina propria was mainly localized at the submucosal lymphatics. Histology of the small intestine of human alcoholics was, more or less, similar to those observed in alcoholic rats. We further investigated the gamma-GTP activity in the mesenteric lymph using the animal model of lymphorrhea, and found that the gamma-GTP activity was increased by 83% when expressed per unit of lymph in the ethanol-fed rat, accompanied by a marked decrease of serum gamma-GTP activity, suggesting a close relationship between the serum and the intestinal gamma-GTP via the lymphatic channel.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗
PubMed1988

Fluctuation of insulin resistance in a leprechaun with a primary defect in insulin binding.

A 3-month-old female leprechaun demonstrated extreme insulin resistance with hyperinsulinemia (330 mumol/L) and resistance to exogenous insulin. Insulin binding to erythrocytes, cultured lymphocytes, and fibroblasts from the patient were decreased to less than 20% of normal, whereas insulin-like growth factor I binding to fibroblasts was normal. Antiinsulin receptor antibody binding to cultured lymphocytes was also decreased to 20% of normal, indicating a decreased concentration of insulin receptors on the cell surface. The ability of insulin to stimulate D-[14C]glucose uptake was decreased to 35% of normal in the patient's fibroblasts, and the dose-response curve was shifted to the right. With time, the insulin resistance fluctuated from near normal (fasting insulin, 244.0 pmol/L) to severe resistance (fasting insulin, 5740-9328 pmol/L), and an insulin tolerance test revealed amelioration of insulin resistance during remission. However, insulin binding to erythrocytes and adipocytes was decreased persistently to 20% of normal. These results indicate that the patient had a primary defect in her insulin receptors, i.e. decreased insulin receptor concentration. The variable degree of insulin resistance was possibly due to variable receptor function in the signal transmission process.

Adipose Tissue↗
PubMed1988

Alteration of insulin-receptor kinase activity by high-fat feeding.

It has been demonstrated in in vivo and in vitro experiments that high-fat (HF) feeding causes insulin resistance. To elucidate the mechanism for this effect, we have measured the kinase activity of the insulin receptor purified from livers of HF-fed rats that showed impaired insulin action in isolated rat adipocytes. In adipocyte experiments, HF feeding led to a 65% decrease in the maximal response stimulated by insulin in a 2-deoxyglucose uptake study. Although insulin binding to adipocytes of HF-fed rats also decreased to 50% of control due to decreased binding affinity, the postbinding defect should be accounted for by decreased insulin action in view of the presence of spare receptor. In contrast to adipocytes, insulin binding to the lectin-purified insulin receptor from livers showed no difference in receptor-binding affinity between HF-fed and control rats. Insulin-stimulated phosphorylation of the beta-subunit of the insulin receptor was decreased to almost 50% throughout the entire dose-response curve. The study of glutamine-tyrosine (4:1) phosphorylation by the insulin-receptor kinase showed results similar to those of the autophosphorylation study. These results suggest that an HF diet causes insulin resistance by affecting insulin-receptor kinase, which plays an important role in transmembrane signaling between insulin binding and insulin action.

Adipose Tissue↗
PubMed1988

Clarification of signaling pathways mediated by insulin and insulin-like growth factor I receptors in fibroblasts from patients with specific defect in insulin receptor.

Receptor binding and biological action of insulin and insulin-like growth factor I (IGF-I) were studied in fibroblasts from a patient with leprechaunism and a patient with type A syndrome of insulin resistance. Insulin binding was reduced to 18.8 and 27.7% of control value, respectively. In contrast, IGF-I binding was normal in both patients. In competitive binding studies, IGF-I had 0.2% of the ability of insulin to compete with 125I-labeled insulin binding, and insulin had 0.1% of the ability of IGF-I to compete with 125I-labeled IGF-I binding in control subjects and patient fibroblasts. The dose-response curves of insulin stimulation assessed by glucose incorporation and alpha-aminoisobutyric acid uptake showed normal responsiveness, and ED50 was significantly shifted to the right in fibroblasts from both patients. However, normal responsiveness and sensitivity were observed in thymidine incorporation studies. For IGF-I, dose-response curves of glucose incorporation, alpha-aminoisobutyric acid uptake, and thymidine incorporation were all normal in both patients. These results indicate that 1) the defect is specific to the insulin-receptor binding in these patients, 2) insulin and IGF-I activate glucose incorporation and alpha-aminoisobutyric acid uptake mainly through their own specific receptors, but 3) the IGF-I receptor appears to have a more important role in stimulating thymidine incorporation than the insulin receptor in physiological condition or, alternatively, an unknown postreceptor process with cascade signal transmission may overcome the decreased insulin-receptor binding to produce a normal dose-response curve.

Aminoisobutyric Acids↗
PubMed1988

Insulin resistance by uncleaved insulin proreceptor. Emergence of binding site by trypsin.

Two sisters presented with severe insulin resistance and markedly decreased insulin binding to erythrocytes, cultured fibroblasts, and transformed lymphocytes. The dose-response curve of insulin-stimulated amino acid uptake in the fibroblasts was shifted to the right. The molecular weight of the insulin receptor on the transformed lymphocytes from the patients was 210,000 and could not be dissociated to alpha- and beta-subunits by dithiothreitol treatment. However, the proreceptor was cleaved by trypsin, and this led to production of a 135,000-Mr alpha-subunit. Insulin binding to the trypsin-treated cells increased to the normal level, and insulin action was normalized. These results suggest that the failure of proreceptor cleavage produces hormone-resistant states and that a proreceptor syndrome may be a unique disease entity for hormone resistance.

Adult↗
PubMed1988

Deficiency of cardiac beta-adrenergic receptor in streptozocin-induced diabetic rats.

The number of beta-adrenergic receptors in cardiac myocytes isolated from rats made diabetic with streptozocin (STZ) for 10 wk was measured by use of a hydrophilic nonselective antagonist [3H]CGP 12177 and was found to decrease to 59% of the number in control rats (P less than .05), without any change in affinity. Similarly, using [125I]iodocyanopindolol as a ligand, we found a decrease in the beta-adrenergic-receptor number on cardiac plasma membrane isolated from the diabetic rats [29% decrease (P less than .05) at 1 wk, 50% (P less than .01) at 3 wk, and 49% (P less than .01) at 10 wk compared with control rats]. However, the serum triiodothyronine level that had been known to modulate the beta-adrenergic-receptor-adenylate cyclase system was decreased in the 1-wk-diabetic rats but not in the 10-wk-diabetic rats compared with each control group. Furthermore, there was no difference in urinary catecholamine excretion between diabetic and control groups. In the 10-wk-diabetic rats, the response of adenylate cyclase to isoproterenol was significantly defective (56% decrease compared with control rats; P less than .05), although both the basal and the forskolin-stimulated maximum adenylate cyclase activities and a half-maximum concentration of isoproterenol for the stimulation of adenylate cyclase were similar in control and diabetic rats. On the other hand, both cholera toxin-dependent and islet-activating protein-dependent [32P]NAD incorporations into cardiac plasma membrane were markedly increased in the diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1988

Improvement of glucose tolerance in NIDDM by clofibrate. Randomized double-blind study.

A randomized double-blind study was performed to examine the effect of clofibrate on glucose tolerance in subjects with non-insulin-dependent diabetes mellitus (NIDDM). Clofibrate (1.5 g/day) or placebo was administered to 70 patients and an oral glucose tolerance test (OGTT) was performed before and 12 wk after treatment. Blood glucose levels were significantly improved in clofibrate-treated groups at all time points during OGTT, whereas there was no change in insulin levels. Improvement of fasting glucose levels required 8 wk of clofibrate treatment. Insulin binding to erythrocytes demonstrated no significant change in the clofibrate-treated subjects. These results suggest that clofibrate improves glucose tolerance in NIDDM subjects without a change in insulin receptors and that clofibrate increases insulin sensitivity through an unknown postreceptor mechanism.

Blood Glucose↗
PubMed1987

Transport and post-transport abnormalities of glucose metabolism in cardiocytes isolated from streptozotocin-induced diabetic rats.

The altered glucose utilization in cardiocytes isolated from streptozotocin (STZ)-induced diabetic rats and its reversibility to normal following 2-week insulin treatment were studied. 3-O-Methylglucose (3-O-MG) transport in cardiocytes isolated from normal rats was stimulated to 150% (P less than 0.01) above the basal level in the presence of 80 nM insulin. The basal 3-O-MG transport in diabetic rats was decreased to 41% of that in normal rats, and further an increase in 3-O-MG transport was not observed even in the presence of 80 nM insulin. Similar significant decreases in glucose uptake in the presence of both trace (0.8 microM) and 5.5 mM glucose were also found in diabetic rats. However, in normal rats, lactate release into the media was stimulated by only 16% (P less than 0.05), and glucose oxidation was not stimulated in the presence of insulin, there being no significant difference between normal and diabetic rats. On 2-week insulin treatment of diabetic rats, both the basal 3-O-MG transport and glucose uptake in the presence of trace and 5.5 mM glucose returned to normal levels, with significant improvement of the blunted acute insulin action. In addition, both lactate release and glucose oxidation were also significantly (P less than 0.05) increased by in vivo insulin treatment. The maximum insulin-stimulated 3-O-MG transport (r = -0.79, P less than 0.01) and glucose uptake in cells in the presence of 5.5 mM glucose (r = -0.74, P less than 0.01) both showed a negative correlation with the plasma glucose concentration, but not with the plasma free fatty acid level or the plasma triglyceride level.(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗
PubMed1987

Study of insulin response to oral glucose load after acute and chronic glycemic control in type 2 diabetic subjects.

To investigate whether correction of fasting hyperglycemia per se improves the insulin secretion in type 2 diabetic subjects, plasma insulin response to 75 g oral glucose load has been studied after acute and chronic normalization of fasting plasma glucose levels in 7 overt type 2 diabetic subjects. For the acute normalization of elevated fasting plasma glucose levels, an artificial endocrine pancreas was employed. Although fasting plasma glucose concentrations were normalized before the oral glucose challenge, insulin response to oral glucose was not improved compared to those without normalization of fasting plasma glucose levels. After 1-3 month control of hyperglycemia, the insulin response to glucose in the subjects was significantly improved compared to those without treatments. Results indicate that chronic metabolic control is essential for the improvement of insulin response to glucose in type 2 diabetic subjects, and also suggest that the impaired insulin secretion in type 2 diabetes is not due to hyperglycemia per se, but due to the metabolic derangements which lead to chronic hyperglycemia.

Adult↗