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Biomedical subjects

Y Shigeta

Publications and source records attributed to Y Shigeta.

At least 73 records · Page 4Linked to original sources
PubMed1993

Atrial natriuretic peptide inhibits endothelin-1-induced activation of mitogen-activated protein kinase in cultured rat mesangial cells.

In cultured rat glomerular mesangial cells, endothelin-1 (ET-1) activated both pp 44 and pp 42 mitogen-activated protein (MAP) kinases. Atrial natriuretic peptide (ANP) inhibited ET-1-induced activation of both pp 44 and pp 42 MAP kinases. ANP also inhibited ET-1-induced translocation of protein kinase C (PKC) and TPA-induced activation of MAP kinase. These results indicate that ANP modulates the functions of mesangial cells, including proliferation and contraction through the inhibition of ET-1-induced activation of MAP kinase in various steps proximal to MAP kinase.

Animals↗
PubMed1993

Src homology 2 domains of protein tyrosine phosphatase are phosphorylated by insulin receptor kinase and bind to the COOH-terminus of insulin receptors in vitro.

To clarify the role of protein tyrosine phosphatases(PTPase) containing Src homology 2 (SH2) regions on insulin signaling, we investigated the interactions between SH2 regions of PTPase and insulin receptors. We made a pair of SH2 domains of PTP1C and SH-PTP2 fusion proteins coupled to glutathione-S-transferase (GST) using pGEX-3X expression vector. After incubating with insulin, insulin receptors were incubated with SH2 proteins in the presence of 100 mu ATP at 4 degrees C for 3 hr, and then immunoprecipitated and analyzed by SDS-PAGE. We found that SH2 domains of SH-PTP2 were phosphorylated, but not those of PTP1C by insulin receptor kinase and the SH2 domains of SH-PTP2, but not those of PTP1C, directly bound to the phosphorylated COOH-terminus of insulin receptors in vitro.

Amino Acid Sequence↗
PubMed1993

Antagonist for atrial natriuretic peptide receptors ameliorates glomerular hyperfiltration in diabetic rats.

To evaluate the possible contribution of atrial natriuretic peptide (ANP) to the development of glomerular hyperfiltration, we examined the effect of non-peptide competitive antagonist for biological receptors of ANP, HS-142-1, on glomerular filtration rate (GFR) and renal plasma flow (RPF) in diabetic rats. Increased GFR and RPF in diabetic rats were significantly ameliorated by the injection of HS-142-1, while blood pressure remained unchanged. Urinary cyclic GMP excretion was significantly higher in diabetic rats than in control rats and HS-142-1 decreased urinary cGMP excretion significantly. These results indicate that atrial natriuretic peptide contributes to the development of glomerular hyperfiltration and hyperperfusion in diabetes and HS-142-1 might be useful in the treatment of them.

Animals↗
PubMed1993

Biological receptors mediate anti-proliferative action of atrial natriuretic peptide in cultured mesangial cells.

The mechanism of anti-proliferative action of atrial natriuretic peptide (ANP) was examined in cultured mesangial cells. HS-142-1, a selective antagonist for ANP biological receptors, inhibited ANP-induced cellular cGMP accumulation and prevented ANP-induced inhibition of both serum-stimulated incorporation of 3H-thymidine and cell proliferation. Des-[Gln18, Ser19, Gly20, Leu21, Gly22]-ANP4-23-NH2 (C-ANP) failed to inhibit 3H-thymidine incorporation. These results indicate that anti-proliferative action of ANP is mediated by the biological receptors in cultured mesangial cells.

Animals↗
PubMed1993

Nipradilol inhibits rat mesangial cell mitogenesis through the activation of soluble guanylate cyclase.

Nipradilol is a beta-adrenoreceptor blocking agent, whose structure contains an NO2 group. Thus, it is possible that it modulates the function of glomerular mesangial cells through the activation of soluble guanylate cyclase. To prove this hypothesis, we examined the effect of nipradilol on soluble guanylate cyclase, intracellular cyclic guanosine monophosphate (cGMP) accumulation, and the mitogenesis of cultured rat glomerular mesangial cells. Nipradilol increased intracellular cGMP accumulation in a dose-dependent manner through the activation of soluble guanylate cyclase. Furthermore, nipradilol inhibited the incorporation of [3H]thymidine into the mesangial cells stimulated by 2.5% fetal bovine serum in a dose-dependent manner. These results indicate that nipradilol may modulate mesangial cell function through an increase in intracellular cGMP resulting from the activation of soluble guanylate cyclase.

Adrenergic beta-Antagonists↗
PubMed1993

Effects of verapamil on the cardiac alpha 1-adrenoceptor signalling system in diabetic rats.

We evaluated the effects of chronic verapamil treatment on the cardiac alpha 1-adrenoceptor signalling system in streptozocin-induced diabetic rats. The decrease in maximum cell surface [3H]bunazosin binding (Bmax) in isolated cardiac myocytes from the diabetic group (-46%, P < 0.01) was completely reversed by a 4-week course of verapamil, while Bmax in the verapamil-treated control group was unchanged. Similarly, the reduction in ventricular inositol 1,4,5-trisphosphate (IP3) production after stimulation with 10 microM noradrenaline (NA) seen in diabetes (-30%, P < 0.01) was completely normalized by verapamil, while the response in the verapamil-treated control group was unaffected. These results indicate that verapamil can induce complete recovery of the impaired cardiac alpha 1-adrenoceptor signalling system in the diabetic heart without affecting glucose metabolism.

Animals↗
PubMed1993

Differential modulation of mitogenic and metabolic actions of insulin-like growth factor I in rat glomerular mesangial cells in high glucose culture.

In order to explore the possible contribution of insulin-like growth factor I to the development of diabetic nephropathy, the effect of glucose on the mitogenic and metabolic actions of insulin-like growth factor I in cultured rat glomerular mesangial cells was examined. The stimulation of [3H]-thymidine incorporation by insulin-like growth factor I in the cells exposed to high concentrations (55 mmol/l) of glucose (4.6 +/- 1.3 fold stimulation) was significantly suppressed as compared with that in the cells cultured in 11 mmol/l glucose (17.5 +/- 0.8 fold). In contrast, [3H]-amino-isobutylic acid uptake into the mesangial cells was significantly enhanced by glucose (2.03 +/- 0.03 nmol.mg protein-1. 15 min-1 at 55 mmol/l glucose vs 0.59 +/- 0.01 at 11 mmol/l glucose), while 2-deoxyglucose uptake remained unchanged. [125I]-insulin-like growth factor I binding was slightly but significantly increased in the cells exposed to high concentrations of glucose. Thus, glucose may modulate the mitogenic and metabolic actions of insulin-like growth factor I differently in cultured mesangial cells probably at the post-insulin-like growth factor I receptor level. These results may indicate that the differential modulation of the actions of insulin-like growth factor I by glucose could result in the increase in amino acid uptake and decrease in the cell proliferation in the mesangial cells, possibly leading to enhanced mesangial matrix synthesis with a relatively small increase in mesangial cell volume as seen in diabetic nephropathy.

Aminoisobutyric Acids↗
PubMed1993

An application of autoregressive model to pattern discrimination of brain electrical activity mapping.

Using the autoregressive model, we developed a method of illustrating significant regional differences between two records of brain electrical activity mapping. This new approach of brain electrical activity mapping analysis through a statistical taxonomy may be clinically useful for evaluation of the normal development of EEG in children and for localizing functional brain abnormality.

Brain↗
PubMed1993

Current status of type 2 (non-insulin-dependent) diabetic subjects on dialysis therapy in Japan.

According to a national survey of dialysis patients in Japan conducted by the Japanese Society for Dialysis Therapy, there were 1,033 patients on dialysis in the Shiga area which has a population of about 1.2 million. Of these 1,033 dialysis patients 140 were the result of diabetic nephropathy. From four hospitals affiliated to Shiga University of Medical Science the medical records of 90 diabetic subjects on dialysis therapy were reviewed and various clinical parameters were analysed and compared with those of patients with chronic glomerulonephritis. Since only one patient had Type 1 (insulin-dependent) diabetes, the remaining 89 with Type 2 (non-insulin-dependent) diabetes were used for this study. The significantly different variables between patients with Type 2 diabetes and chronic glomerulonephritis were age (60.4 vs 54.6 years, p < 0.05), BMI (22.4 vs 20.6 kg/m2, p < 0.001), cardiothoracic ratio (56.4 vs 53.3%, p < 0.001), mean blood pressure (110 vs 117 mmHg, p < 0.05), serum creatinine (9.0 vs 11.5 mg/dl, p < 0.001), serum urea-N (98.2 vs 115.5 mg/dl, p < 0.001), serum total protein (6.0 vs 6.5 g/dl, p < 0.001) and serum albumin (3.5 vs. 3.9 g/dl, p < 0.001). Serum levels of cholesterol and triglyceride were not significantly different between two groups, though the prevalence of electrocardiogram abnormalities, oedema, neuropathy, myocardial infarction and cerebrovascular diseases was significantly higher in the Type 2 diabetic group. These results suggested that Type 2 diabetic patients with end-stage renal disease were older, more malnourished, fluid overloaded and multi-morbid as a result of vasculopathy and neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1993

Electrophysiological study of dorsal column function in streptozocin-induced diabetic rats: comparison with 2,5-hexanedione intoxication.

Dorsal column function and peripheral motor and sensory conduction velocities (MCV, SCV) were evaluated in experimental diabetic rats and compared with those in 2,5-hexanedione (2,5-HD) intoxicated rats. Hyperglycemia was induced by a single injection of streptozocin, and electrophysiological studies were performed 4 and 12 weeks after the injection. For 8 weeks 2,5-HD was administered daily by drinking water to make the 2,5-HD neuropathy rats. Age-matched rats were used as control. In diabetic rats, gracile surface potentials evoked by electrical stimulation of the lumbosacral trunk remained normal during the experimental period, whereas the N and P waves of the evoked potentials were suppressed and the duration of the N wave was prolonged in the 2,5-HD rats. In 4-week diabetic rats, the antidromic compound action potentials of the gracile tract recorded at the most proximal site of lumbosacral trunk were normal. In 12-week diabetic rats, the gracile tract conduction velocity (GTCV) was decreased, although the duration of these potentials was normal. By contrast, the GTCV was decreased and the duration was markedly prolonged in 2,5-HD rats. These findings might indicate that temporal dispersion of incoming volleys in the gracile tract is increased in 2,5-HD rats, but not in diabetic rats. These results suggest that diabetic myelopathy exists that but the magnitude and progression of this condition are quite different from those of 2,5-HD intoxication, typical dying-back-type neuropathy and that the dorsal column is less vulnerable than the peripheral nerve in diabetes mellitus.

Animals↗
PubMed1993

Effect of medium pH on glutathione redox cycle in cultured human umbilical vein endothelial cells.

Impairments of the glutathione redox cycle in cultured endothelial cells under acidic pH conditions were measured. Glutathione-dependent H2O2-degrading activities decreased by 20% (P < .01) at pH 6 and by 51% (P < .01) at pH 4 compared with activities at pH 7.4 1 hour after a change with fresh medium. Intracellular reduced glutathione (GSH) content increased by 85% (P < .01) following the change with pH 7.4 medium. Such increases in GSH content were impaired after exposure to acidic medium. After exposure to 500 mumol/LH2O2, intracellular GSH content decreased by 61% compared with the level obtained in the absence of H2O2 at pH 7.4 (P < .01). Compared with the level at pH 7.4, the H2O2-induced decrease in intracellular GSH content was 32% lower (P < .01) at pH 6 and did not change at all at pH 4. After exposure to 500 mumol/L H2O2, the intracellular oxidized glutathione (GSSG) content increased by 160% at pH 7.4 (P < .01), 370% at pH 6 (P < .01), and 90% at pH 4 compared with treatment without H2O2, respectively. After exposure to 500 mumol/L H2O2, the release of GSSG from cells at pH 6 decreased by 38% compared with the value found at pH 7.4 (P < .05), and the release at pH 4 completely disappeared. Both glutathione peroxidase (GPO) and glutathione reductase activities decreased as a function of a decrease in pH from 7.4 to 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Acids↗
PubMed1993

Alteration of mesangial response to ANP and angiotensin II by glucose.

To test the hypothesis that the function of glomerular mesangial cells is impaired in diabetes, we examined the responsiveness of mesangial cells cultured under high concentrations of glucose to atrial natriuretic peptide (ANP1) and angiotensin II (Ang II). The ANP-induced accumulation of cGMP was enhanced in mesangial cells cultured under high glucose conditions, possibly due to the activation of particulate guanylate cyclase. Ang II action in mesangial cells was evaluated by measuring the ability of Ang II to inhibit ANP-induced cGMP accumulation through both activating phosphodiesterase (initial phase) and inhibiting guanylate cyclase (maintenance phase). The inhibition of both ANP-induced cellular cGMP accumulation and particulate guanylate cyclase activity by Ang II was significantly reduced in mesangial cells cultured under high concentrations of glucose. Moreover, in the cells exposed to high concentrations of glucose, both basal and Ang II-stimulated levels of inositol 1,4,5-trisphosphate (IP3) were significantly reduced. These results indicate that, in high glucose conditions, the actions of ANP and Ang II are modulated differently, resulting in the impairment of contractile responsiveness of mesangial cells.

Angiotensin II↗
PubMed1993

[Effect of glucose on soluble guanylate cyclase in cultured rat mesangial cells].

The intracellular content of cyclic GMP (cGMP) is known to mediate the effects of various vasodilating substances on glomerular mesangial cells. However, little is known about the role of soluble guanylate cyclase (SGC) in these cells in diabetes. We, therefore, investigated the changes in SGC activity as well as the cGMP content in rat mesangial cells (MC) cultured under high glucose or hypertonic conditions. The following results were obtained. 1. Sodium nitroprusside (SNP) (10(-4) M, 10min.) increased cyclic GMP (cGMP) content in MC from 8.17 +/- 0.99 pmol/mg protein to 981.6 +/- 86.3. 2. SNP (10(-4) M) stimulated SGC activity from 38.3 +/- 10.8 pmol cGMP formed/mg protein/10 minutes to 74.4 +/- 5.2. 3. In the coincubation experiment with bovine aortic endothelial cells, bradykinin (10(-6) M, 10min.) increased cGMP content in MC from 6.24 +/- 1.35 to 348.3 +/- 45.3. However, 4. the activity of SGC and SNP-induced increase of cGMP were not influenced by culturing MC in high glucose or hypertonic media. Similarly, the cGMP increase in MC coincubated with BAEC under bradykinin stimulation was not altered by culturing under high glucose or hypertonic conditions. These data suggested that SGC may play an important role in the regulation of cGMP content in MC. However, this enzyme may not be involved in the increase of cGMP content in MC cultured under high glucose condition.

Animals↗
PubMed1993

[Hypoglycemia].

Explore the source record for details and available documents.

Adolescent↗
PubMed1992

[A case of Cushing syndrome caused by ACTH producing atypical lung carcinoid tumor].

A forty-one-year-old male who was found to have lung carcinoid tumor showed clinical features of Cushing syndrome. At the age of 38 years during a regular check-up, a chest roentgenogram showed multiple nodular shadows in the bilateral lung, and he was admitted to hospital. By open lung biopsy, he was diagnosed as having malignant carcinoid or small cell carcinoma of the lung. The abnormal lung shadows did not respond to chemotherapy (CDDP + VDS). The clinical course after discharge was uneventful until the age of 41 years, when he was readmitted to our hospital because of brain metastasis. Physical examination revealed moon face and central obesity. Plasma ACTH level was high and dexamethasone suppression test showed no cortisol suppression on 8 mg dexamethasone administration. Therefore, it was thought that the patient had ACTH producing ectopic tumor which led to Cushing syndrome. We measured the molecular weight of ACTH by column chromatography and found he had a big ACTH (molecular weight about 22,000). Reexamining him clinically and histologically, we concluded that the patient had atypical carcinoid tumor in the lung which might produce ACTH causing Cushing syndrome with metastasis to the brain.

Adrenocorticotropic Hormone↗
PubMed1992

Increased plasma post-heparin diamine oxidase activity and plant sterol levels in streptozotocin diabetic rat.

Plasma post-heparin diamine oxidase (DAO) activity and plasma levels of plant sterols were examined in streptozotocin diabetic rats fed with chow containing plant sterols, to investigate the enzyme activity in relation to the morphological changes of small intestine as well as sterol absorption in the diabetic rats. Diabetic rats showed increased small intestinal mass and surface area compared with control rats. Plasma post-heparin DAO activity and plant sterol level were also increased more than 2.5-fold in the diabetic rats. Insulin treatment improved these abnormalities. Plasma DAO activity correlated to both the small intestinal hyperplastic change and plasma plant sterol levels. These results indicate that plasma post-heparin DAO activity may be used as a marker of intestinal hypertrophy as well as ability to absorb dietary sterols.

Amine Oxidase (Copper-Containing)↗
PubMed1992

Characterization of unprocessed insulin proreceptors in COS 7 cells transfected with cDNA with Arg735----Ser735 point mutation at the cleavage site.

We previously reported on patients with severe insulin resistance due to unprocessed insulin proreceptors. A structural change of the cleavage site from Arg-Lys-Arg-Arg to Arg-Lys-Arg-Ser due to G----T point mutation appeared to be the cause for failure to process the proreceptors. To determine whether the mutation of insulin proreceptors at the cleavage site was responsible for unprocessed insulin receptors and to elucidate the structural and binding characteristics of the proreceptors, we transfected cDNA with the mutation in COS 7 cells and examined the expressed insulin receptors. At 72 hours after transfection, insulin binding increased to the maximum in cells transfected with either normal or mutated cDNA, and insulin binding was 40 and 14 times higher than that of nontransfected cells, respectively. The declining rate of insulin binding after reaching the maximum was delayed in cells transfected with mutated cDNA. Affinity cross-linking and surface-labeling studies showed a 135-kilodalton (kD), normal alpha-subunit in the cells transfected with normal cDNA and a 210-kD proreceptor in the mutant cells. The proreceptors were cleaved by trypsin to yield normal-sized alpha- and beta-subunits. The sensitivity to trypsin was similar to that demonstrated in patients' cells, and the most effective concentration for the cleavage was 0.025%. Autophosphorylation resulted in decreased 32P incorporation into proreceptors of cells transfected with mutated cDNA at both basal and insulin-stimulated states, without a change in insulin sensitivity. Competitive binding studies with insulin, proinsulin, and miniproinsulin showed that the proreceptors had a lower relative affinity for proinsulin, but this characteristic disappeared after trypsin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗