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Biomedical subjects

Y Shigeta

Publications and source records attributed to Y Shigeta.

318 records · Page 18Linked to original sources
PubMedDate not supplied

High blood pressure is a risk factor for the development of microalbuminuria in Japanese subjects with non-insulin-dependent diabetes mellitus.

In this study, 52 nonproteinuric Japanese patients with non-insulin-dependent diabetes (NIDDM) were followed from 1985 to 1990 to investigate the rate of development and progression of microalbuminuria and the factors which influence it. In 1985, 34 patients were normoalbuminuric, and 18 patients were microalbuminuric. Five years later, 11 of 34 initially normoalbuminuric patients (32.4%) developed microalbuminuria, and 6 of 18 initially microalbuminuric patients (33.3%) developed overt proteinuria. At the beginning of the study, hypertension existed more frequently in the patients who later developed microalbuminuria (8 of 11, 72.7%) than in the patients who stayed normoalbuminuric (4 of 23, 17.4%). Age-adjusted values of mean blood pressure (+/- SEM) at the beginning of the study in the patients who developed microalbuminuria (98.2 +/- 3.4 mm Hg, n = 11) were significantly higher than those in the patients who stayed normoalbuminuric (87.3 +/- 2.4 mm Hg, n = 23). In six patients who developed overt proteinuria, initial urinary albumin excretion rates (AER) were higher than those in the patients who stayed microalbuminuric, and four patients who presented with initial AER greater than 100 micrograms/min all developed overt proteinuria. These results indicate that, in Japanese patients with NIDDM, the rate of development of microalbuminuria is faster than that reported in Caucasian IDDM, and preexisting hypertension with relatively poor control of blood pressure may be a risk factor for the development of microalbuminuria.

Adult↗
PubMedDate not supplied

Significance of fructose-induced protein oxidation and formation of advanced glycation end product.

To investigate the significance of fructose-induced protein modification, we examined both fructose- and glucose-induced protein oxidation and the formation of advanced glycation end products (AGE) in vitro. Albumin incubated in the presence of 100 mM fructose at 37 degrees C for 1 week showed 5.1-fold and 3.1-fold increases in the content of carbonyl, which is a marker for oxidized protein, when compared with either control incubated without sugar or with 100 mM glucose. Similarly, the same incubation with fructose increased the fluorescence intensity over 100-fold and 15-fold formation compared with that of no sugar and glucose controls, respectively. Both fructose-induced fluorescence and protein oxidation were almost completely suppressed in the presence of the iron chelator; deferoxamine (100 microM), the hydroxyl radical scavenger; MK-447 (1 mM), or aminoguanidine (200 mM), which is an inhibitor of AGE formation. In contrast, the fructose-induced formation of fluorescent albumin was potentiated in the presence of 100 microM FeCl2. This was completely inhibited in the presence of 60 microM or more deferoxamine. These results suggest that fructose promotes both AGE formation and protein oxidation possibly through the formation of hydroxyl radicals.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Abnormalities in protein kinase C and MAP kinase cascade in mesangial cells cultured under high glucose conditions.

In order to clarify the mechanism of mesangial cell dysfunction in diabetes, we examined the activities of protein kinase C (PKC) and mitogen-activated protein kinase (MAPK), important kinases in various cellular functions, and also evaluated the isoenzymes of PKC in mesangial cells cultured under high glucose conditions. Exposure of cells to high concentrations (27.8 mM) of glucose for 5 days resulted in a significant elevation of PKC activities in the membrane fraction. MAPK was also activated in cells cultured under high glucose conditions. Of the PKC isoenzymes, the levels of PKC alpha and zeta were significantly increased in the membrane fraction after 5 days of exposure to high concentrations of glucose. These results indicate that the translocation of PKC alpha and zeta and the activation of MAPK under high glucose conditions might be underlying mechanisms of the functional disturbance of mesangial cells in diabetes.

Animals↗
PubMedDate not supplied

Cyclic nucleotides attenuate endothelin-1-induced activation of mitogen-activated protein kinase in cultured rat mesangial cells.

In order to clarify the mechanisms of interaction between endothelin-1 (ET-1) and cyclic AMP (cAMP) or cyclic GMP (cGMP), we examined the effects of cAMP or cGMP on ET-1-induced activation of mitogen-activated protein kinase (MAPK), one of the key enzymes in the signal transduction of ET-1, in cultured rat mesangial cells. ET-1 was able to activate both p42 and p44 MAP kinases in a dose-dependent manner. Cell permeable analogues of cAMP and cGMP, dibutylyl cAMP (BT2-cAMP) and 8 bromo cGMP (8br-GMP), significantly inhibited ET-1-induced activation of MAPK. Atrial natriuretic peptide (ANP), which increased cellular cGMP, was able to inhibit ET-1-induced activation of MAPK in a dose-dependent manner, while c-ANP, an analogue specific to the clearance receptors of ANP, exerted no effect. These results indicate that cAMP and cGMP could modulate the action of ET-1 in mesangial cells at a step of the activation of MAPK.

Animals↗
PubMedDate not supplied

Microalbuminuria cannot predict cardiovascular death in Japanese subjects with non-insulin-dependent diabetes mellitus.

In order to examine whether the existence of microalbuminuria can predict the development of overt proteinuria and cardiovascular death in Japanese subjects with non-insulin-dependent diabetes mellitus (NIDDM), we investigated 47 patients for a 10-year follow-up period. Patients were divided into two groups by the initial values of urinary albumin excretion rates. The percentage of patients who developed overt proteinuria during the follow-up period was significantly higher in patients who were initially classified as microalbuminuric group (63.6%) than in normoalbuminuric group (17.4%). During the follow-up period, one of the patients with normoalbuminuria had died of congestive heart failure, while four of those with microalbuminuria had died; one of stroke and three from noncardiovascular diseases. These results indicate that the existence of microalbuminuria had the predictive power for the development of overt proteinuria, but not for cardiovascular death in Japanese subjects with NIDDM.

Albuminuria↗
PubMedDate not supplied

Clinical investigation of epalrestat, an aldose reductase inhibitor, on diabetic neuropathy in Japan: multicenter study. Diabetic Neuropathy Study Group in Japan.

A number of diabetic patients with diabetic neuropathy were treated with epalrestat, an aldose reductase inhibitor, since this drug was launched into the market in Japan. More than 5000 patients with diabetic neuropathy who were treated with epalrestat for 3-12 months were treated to analyze the efficacy and the adverse reactions of the drug in this study. The improvement rates of subjective symptoms (i.e., spontaneous pain, numbness, coldness, and hypoesthesia) was 75% (slightly improved or better) and those of nerve function tests (i.e., motor nerve conduction velocity, sensory nerve-conduction velocity, and vibration threshold) 36%. Adverse drug reactions were encountered in 129 cases (2.5%) out of 5249 patients, none of which were severe ones. Although data are limited, they strongly suggest that epalrestat is a highly effective and safe agent for the treatment of diabetic neuropathy.

Adult↗
PubMedDate not supplied

Metabolism of a mutant insulin by a receptor-mediated process and an insulin degrading enzyme.

The metabolism of a mutant insulin, [LeuB25]-insulin, was studied in vitro and in vivo. Porcine or mutant insulin (4 micrograms/kg body weight) was injected i.v. into streptozotocin-induced diabetic rats and their plasma glucose and insulin levels were determined. The half-lives of porcine and mutant insulin were 3 min and 18 min, respectively. The ability of the mutant insulin to lower the blood glucose levels was 38% of that of normal when the glucose levels at the nadir were compared. Receptor-mediated degradation of the mutant insulin assessed by chromatography of the degraded materials in the media after incubation with cells was less compared with that of porcine insulin (4% vs. 24%). The media containing the insulin degrading enzyme (IDE) of IM-9 cells and rat livers degraded porcine and mutant insulin to the same extent. These results suggest that the decreased clearance of insulin is due to the decreased receptor binding and the decreased receptor-mediated degradation, but is not due to the decreased degradation by IDE.

Animals↗
PubMedDate not supplied

Insulin binding to differentiating muscle cell line L6.

We studied insulin binding to cultured differentiating muscle cell line L6. Insulin binding to the cells reached a plateau after incubation with 125I-insulin for 4 h at 22 degrees C, and was at an optimum at pH 7.8. Preincubation with 10 microM of hydrocortisone for 36 h at 37 degrees C resulted in significantly increased insulin binding (1.73 +/- 0.12 ng/mg protein for treated cells vs. 1.13 +/- 0.025 ng/mg protein for control cells, mean +/- SD, P less than 0.001). Preincubation with 1 microM of hydrocortisone or 1 microM of dexamethasone also led to increased binding. The number of insulin-binding sites per cell increased 2.5-fold in glucocorticoid-treated cells (9.7 X 10(3) sites/cell for treated vs. 3.8 X 10(3) sites/cell for control cells). Preincubation with trifluoperazine (5 microM), a calmodulin inhibitor, did not affect insulin binding to the cells. These results indicate that glucocorticoid might have some important role in regulating the number of insulin receptors in L6 muscle cells.

Animals↗
PubMedDate not supplied

A role of mesangial dysfunction in the development of diabetic nephropathy.

The pathogenic mechanism of diabetic nephropathy has been extensively investigated, and the significance of alteration in glomerular hemodynamics or mesangial cell metabolism has been recently clarified. It is expected that in the near future these pathologically important alterations can be corrected, and the development diabetic nephropathy can be halted.

Animals↗
PubMedDate not supplied

Development of paper-strip test for 3-hydroxybutyrate and its clinical application.

A rapid paper-strip test for the semiquantitating 3-hydroxybutyrate (3-OHBA) has been developed. The color develops within 5 min after applying the serum to the paper strip, and the purple color was read either visually or by reflectance meter. This can detect 3-OHBA levels as low as 0.1 mmol/L up to 2.0 mmol/L. The more concentrated sample can be measured on serial dilution. Clinical usefulness has been tested in a summer camp for insulin-dependent diabetic children as well as in a routine diabetes clinic. Serum 3-OHBA levels ranged from greater than 100 mumol/L to 4 mmol/L in all the subjects before breakfast in a summer camp. In four subjects, 3-OHBA was elevated to the level of 2-4 mmol/L, and only one of these four subjects exhibited ketonuria by nitroprusside test. In a diabetes clinic, a new paper-strip test for 3-OHBA has revealed ketonemia in 34 (74%) of 46 diabetic subjects, while nitro-prusside test revealed ketonemia in only 4 (13%). The present paper-strip test for 3-OHBA is sensitive enough to detect levels as low as 0.1 mmol/L and is clinically useful for rapid detection of ketosis proneness as well as for monitoring of diabetes control.

3-Hydroxybutyric Acid↗