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Biomedical subjects

Y Omori

Publications and source records attributed to Y Omori.

At least 109 records · Page 6Linked to original sources
PubMed1995

Pancreatic amylin content in human diabetic subjects and its relation to diabetes.

To evaluate the pancreatic amylin in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM), we determined the pancreatic amylin (IRA) and insulin (IRI) contents of pancreata obtained at autopsy from diabetics and nondiabetics. IRA was extracted from the tail of the pancreas using formic acid and assayed with a human amylin kit. Following gel filtration of amylin on a Sephadex G-50 column, it was eluted in a similar fraction to insulin. The pancreatic IRA content was significantly higher (p < 0.01) in NIDDM subjects compared with nondiabetics, with the mean values being 4.25 +/- 1.62 and 0.085 +/- 0.022 microgram/g, respectively. The IRA content of two IDDM pancreata was low. No significant relationship was found between the IRA and the IRI contents or between the IRA content and the duration of diabetes. However, there was a tendency for the IRA content to increase in longstanding diabetes. Men had a significantly higher pancreatic IRA content than women. The four subjects with very high IRA levels ( > 10 micrograms/g) were all elderly men with a long duration of diabetes. Thus, although the pancreatic amylin content was increased in NIDDM, no significant relationship to the clinical features of the disease was found.

Aged↗
PubMed1995

Highly increased insulin secretion in a patient with postprandial hypoglycemia: role of glucagon-like peptide-1 (7-36) amide.

The mechanism(s) of an inappropriate secretion of insulin is poorly understood. We report a case of reactive hypoglycemia associated with an unusually exaggerated insulin secretion. The patient, a 32-year-old man, developed frequent episodes of postprandial hypoglycemia after interferon treatment was begun for chronic type C hepatitis. Oral glucose challenge test confirmed the patient's extremely high plasma IRI response, i.e., more than 1000 microU/ml, and that of plasma C-peptide 56.9 ng/ml at 90 min, followed by symptomatic hypoglycemia (plasma glucose 34 mg/dl) at 240 min. The plasma proinsulin level also was high, but the molar ratio of immuno reactive insulin (IRI)/plasma C-peptide and IRI/proinsulin was within the normal range. Antibodies to insulin or insulin-receptor were negative. Plasma IRI response was apparently greater when the glucose was given orally than when given intravenously. The response of plasma glucagon-like-peptide (GLP)-1 to oral glucose was quite high (from baseline of 45.5 to 303.2 pmol/L) and showed a close parallel with the change in the plasma IRI concentration. The greatly enhanced insulin secretion leading to reactive hypoglycemia in this patient may therefore be attributed to the increased secretion of GLP-1.

Adult↗
PubMed1995

Pathophysiological significance of plasma total renin and prorenin in patients with diabetes mellitus.

To seek the pathophysiologic significance of measuring the concentration of total renin instead of prorenin, we determined the plasma total renin concentration by immunoradiometric assay and correlated the results with various clinical features and laboratory parameters of diabetic complication in 108 patients with diabetes mellitus. The plasma prorenin concentration was estimated as the difference between the total and active renin concentrations. The plasma total renin and prorenin concentrations were high in patients with diabetes mellitus, in contrast to the active renin concentration which was slightly decreased. In addition, the plasma total renin and prorenin concentrations were higher in patients with diabetic complications than in patients without any complication. Multiple regression analysis showed that the presence of orthostatic hypotension, diabetic retinopathy, and proteinuria is significantly associated with the increased plasma total renin and prorenin concentrations. In addition, there was a significant positive correlation between the total renin and prorenin concentrations. These results suggest that both the plasma total renin concentration and the prorenin concentration are closely related to diabetic complications. Determination of the plasma total renin concentration by immunoradiometric assay as a substitute for prorenin could be a powerful tool in elucidating the mechanism for the increased plasma prorenin in diabetes mellitus.

Adult↗
PubMed1995

Insulin sensitivity and negative insulin feedback after pancreas transplantation in insulin-dependent diabetic patients.

The aims of this study were to determine the change in the rate of insulin-stimulated glucose disposal (insulin sensitivity) and the ability of insulin to inhibit its own secretion in four pancreas-kidney transplant recipients with insulin-dependent diabetes mellitus. Insulin sensitivity (glucose infusion rate, GIR) was measured by a euglycemic hyperinsulinemic clamp technique before and 2, 6 and 12 months after transplantation. The GIR values in the four recipients were normalized within 2 months and remained normal for 12 months after transplantation, despite long-term steroid therapy for immunosuppression. Physiological hyperinsulinemia (50-70 microU/ml) suppressed plasma C-peptide, but its nadirs were still higher than the basal levels in normal controls. Taking into account evidence of a minimal increase in the concentration of circulating insulin that inhibits insulin secretion in healthy subjects and evidence of increased insulin secretion in pancreas recipients, the authors speculate that defective feedback inhibition of insulin secretion could contribute, at least in part, to the disproportionate basal hyperinsulinemia in patients with a denervated, transplanted pancreas in the absence of insulin resistance.

Adult↗
PubMed1995

Effects of acute hyperinsulinemia on plasma atrial and brain natriuretic peptide concentrations.

Impaired renal sodium excretion and increased plasma atrial natriuretic peptide (ANP) levels have been reported in patients with hypertension associated with insulin resistance and hyperinsulinemia. To clarify the interrelationship between hyperinsulinemia and plasma natriuretic peptides, we investigated the effects of physiological and non-physiological hyperinsulinemia on the plasma ANP and brain natriuretic peptide (BNP) levels. Plasma immunoreactive insulin (IRI), ANP and BNP levels were determined by a euglycemic-hyperinsulinemic glucose clamp in 20 patients with non-insulin-dependent diabetes mellitus, by a glucose challenge test in 22 normal subjects and by an insulin challenge test in six normal subjects. Both in the glucose clamp and the glucose challenge test, plasma ANP showed a significant increase in association with increased plasma IRI and plasma volume. However, there was no significant correlation between the changes in plasma ANP levels and plasma IRI levels in view of the peak values and the area under the curve of their responses. In addition, the plasma ANP did not show any significant change despite the marked elevation of plasma IRI in the insulin challenge test. There was no significant change in plasma BNP under any of the hyperinsulinemic conditions. These findings provide in vivo evidence for the lack of a direct effect of acute hyperinsulinemia on natriuretic peptides, although the chronic effects of hyperinsulinemia remain to be elucidated.

Acute Disease↗
PubMed1995

Association of sick sinus syndrome with hyperinsulinemia and insulin resistance in patients with non-insulin-dependent diabetes mellitus: report of four cases.

We report four non-insulin-dependent diabetic (NIDDM) patients accompanied by a unique combination of sick sinus syndrome (SSS) and hyperinsulinemia of unknown etiology. SSS of all four cases was due to sinus arrest in association with paroxysmal atrial fibrillation (Rubenstein-III). Of special interest is that one patient showed a high prevalence of SSS and NIDDM among her close relatives. Hyperinsulinemia of moderate degree was seen at fasting state or after carbohydrate ingestion in the absence of obesity. The resistance to the action of insulin on glucose metabolism which was evaluated in three patients by the euglycemic hyperinsulinemic clamp study was found to be comparable to the lowest quartile level for common NIDDM patients. Because insulin is a physiological regulator of cell-membrane Na+/K+-ATPase, we speculate that malfunction of the sinus node automaticity may be caused by chronic exposure to hyperinsulinemia secondary to insulin resistance in these NIDDM patients.

Aged↗
PubMed1995

Localization of MODY3 to a 5-cM region of human chromosome 12.

Maturity-onset diabetes of the young (MODY) is a heterogeneous disorder that appears to be characterized by a primary defect in insulin secretion. Mutations in an unknown locus (MODY1) on chromosome 20 and the glucokinase gene (MODY2) on chromosome 7 can cause this form of non-insulin-dependent diabetes. Recent genetic studies have identified a third locus on chromosome 12 (MODY3) that is linked to MODY in a group of French families. We have identified three families from Denmark, Germany, and the U.S. (Michigan) showing evidence of linkage with MODY3 and a family from Japan showing suggestive evidence. Analysis of key recombinants in these families localized MODY3 to a 5-cM interval between the markers D12S86 and D12S807/D12S820.

Adult↗
PubMed1995

[Effects of temperature and humidity on the stability of nitric oxide, and efficacy of soda lime as a selective absorber of nitrogen dioxide].

Although inhaled nitric oxide (NO) has attracted attention as a pulmonary vasodilator, little heed has been given to its potential toxicity. Nitric oxide is known to be rapidly oxidized to nitrogen dioxide (NO2), which may damage pulmonary tissue. We examined the effects of temperature and humidity on the production of NO2 from NO. We also evaluated the amount of NO2 absorbed by soda lime, which is usually placed in the inspiratory line. For this purpose, we measured changes over time in the concentrations of NO and NO2 in mixtures that included NO, oxygen, and nitrogen in various concentrations, and at different temperatures and humidities. We confirmed that the formation of NO2 from NO follows the equation: -d[NO]/dt = 2 k[NO]2 [O2], where k is the rate constant. We found that k was significantly smaller at 37 degrees C than at 25 degrees C but was not influenced by humidity (0%, 40% or 90%). Although soda lime was very effective in absorbing NO2 from the inspiratory line, NO was simultaneously absorbed at the same molar ratio when the two gases existed together in the line. We thus conclude that inhalation of NO at 37 degrees C is more desirable than inhalation at room temperature, to suppress the production of NO2. When soda lime is used in the inspiratory line, attention should be paid to the reduction in the concentration of NO in the line.

Absorption↗
PubMed1995

Accumulation of phosphatydilcholine-hydroperoxide in dialysis patients with diabetic nephropathy.

Plasma lipid peroxidation in noninsulin dependent diabetes mellitus (DM) patients were evaluated in DM patients undergoing hemodialysis (HD) by means of a chemiluminescence-HPLC for the specific determination of phosphatidylcholine hydroperoxide (PCOOH). Thirty-three uremic patients with DM nephropathy, undergoing 12 hours HD a week using polymethylmethacrylate membrane, were studied. Of them 22 DM patients on HD were divided into 2 age and sex matched groups treated and conventional group in order to clarify therapeutic effect of 500 mg alfa-tocopherol and 600 mg probucol daily. Fifty DM patients without end-stage renal disease (ESRD) who were age-, period of diabetes-, and sex-matched, were selected as positive control of the subjects. Plasma PCOOH levels were significantly elevated in both DM patients, while the plasma PCOOH in normal controls were 227.0 +/- 68.7 pmol/ml. Plasma PCOOH levels of DM patients undergoing HD were significantly higher than that of patients without ESRD (1,330.8 +/- 642.7 pmol/ml vs. 756.6 +/- 431.9 pmol/ml, p < 0.025). Partial correlation coefficient of plasma PCOOH level demonstrated PCOOH and period of HD in DM patients were highly significantly positively correlated (p < 0.01), although single session of HD was not found to produce significantly increased lipid-peroxidation. Plasma PCOOH roughly remained within similar levels as base lines by medication with anti-oxidant compared to that of conventional group. From these results we conclude that HD intensifies lipid peroxidation and such accumulation of hydroperoxide could account for accelerated progress of atherosclerosis in DM patients with renal insufficiency. It is worthwhile to try an administration of free radical scavenger in order to reduce PCOOH and slow down the progression of atherosclerotic vascular disease.

Adult↗
PubMed1994

Altered homologous and heterologous gap-junctional intercellular communication in primary human liver tumors associated with aberrant protein localization but not gene mutation of connexin 32.

Gap-junctional intercellular communication (GJIC) in 20 primary human liver tumors with different degrees of malignancy has been studied at the functional and molecular levels. When GJIC capacity was determined by dye-transfer assay performed directly with freshly removed tumor tissue, significant reduction was found in all samples, regardless of their morphology. In addition, a selective lack of GJIC between tumor and surrounding non-tumorous cells was observed in some cases, probably due to the physical separation between them resulting from encapsulation of tumors. There was, however, no essential change in the level of expression of the major liver gap-junction protein, connexin (cx) 32, in liver tumors as measured by Northern and Western blot analyses. Immunohistochemical study revealed aberrant localization of cx 32 in the majority of malignant liver tumors. Instead of cytoplasmic membrane localization at intercellular contacts, cx 32 was detected mainly either intracytoplasmically or in plasma membrane free from contact with other cells. We did not detect any mutation in the coding sequence of the cx 32 gene from any of the human liver tumors we tested. Thus it is likely that the aberrant localization of cx 32 in tumor cells is due to disruption of the mechanisms for establishment of this protein into gap-junction plaques, rather than to structural abnormality of the cx 32 protein itself. Another member of the connexin family, cx 43, not detectable in non-tumorigenic hepatocytes, was expressed in several tumors, especially in invasive areas, but was detected in only a few tumor cells and was localized intracytoplasmically, suggesting that cx 43 protein is not involved in GJIC in the tumors.

Adult↗
PubMed1994

Alterations of (CA)n DNA repeats and tumor suppressor genes in human gastric cancer.

We have examined whether alterations of simple (CA)n DNA repeats, as observed in human colon cancers, occur during human gastric carcinogenesis and whether such alterations reflect genomic instability that could lead to other genetic changes. A total of 22 gastric cancer samples were analyzed: 15 well or moderately differentiated adenocarcinomas, 6 signet-ring cell carcinomas, and 1 poorly differentiated adenocarcinoma. When (CA)n repeat sequences were examined at 10 loci, one adenocarcinoma showed a loss of repeat sequences at five loci, three adenocarcinomas gained a repeat at one locus, and one adenocarcinoma had new, repeated sequences at five loci. Three samples showed mutations in the p53 gene, two in exon 5 (both GC to AT transition at a CpG dinucleotide) and one in exon 7 (AT to GC transition). Only one sample with a p53 mutation also showed altered (CA)n repeats. A putative tumor suppressor gene, connexin 32, was not altered as assessed by single-strand conformation polymorphism analysis. These results suggest that genomic instability revealed by (CA)n repeat changes does not seem to contribute to induction of point mutations in p53 or connexin 32 genes but may participate in loss of heterozygosity at APC/MCC loci. The results are consistent with the hypothesis that different mechanisms are involved in the gain and loss of (CA)n repeats.

Adenocarcinoma↗
PubMed1994

High levels of erythrocyte aldose reductase and diabetic retinopathy in NIDDM patients.

Erythrocyte aldose reductase was determined in 90 NIDDM patients by a two-site ELISA using recombinant human aldose reductase. The level of aldose reductase did not correlate with age, duration of diabetes, fasting blood glucose and HbA1c of the patients. Among 38 patients with diabetes for more than 10 years, aldose reductase in those with retinopathy (including non-proliferative and proliferative) was significantly higher than in those without, while no difference in the means of the average HbA1c, maximum and minimum blood pressure levels was observed between the two groups. The results indicate that the level of aldose reductase in the erythrocyte of diabetic patients is associated with the presence of retinopathy.

Adult↗
PubMed1994

Relationship between insulin resistance and risk factors for cardiovascular disease in Japanese non-insulin-dependent diabetic patients.

To investigate whether a resistance to insulin-stimulated glucose uptake (IR) is associated with the risk factors (RF) for cardiovascular disease (CVD) in non-insulin-dependent diabetic (NIDDM) patients, we determined the degree of IR in 135 adult NIDDM patients who had no advanced diabetic complications. The euglycemic (80 mg/dl) hyperinsulinemic clamp (insulin infusion rate 1.12 mU/kg per min) was performed and the average glucose infusion rate (GIR) during a steady-state euglycemia was determined as a measure of IR. Hypertension was more common among NIDDM patients with an increased IR and was highest in the group of patients with CVD. CVD-RF such as hypertension, hypertriglyceridemia, low HDL-cholesterol and obesity tended to cluster in the NIDDM patients who had lower GIR values and higher fasting IRI levels. GIR values were compared between a set of groups extracted from the 135 NIDDM patients that were matched for age, sex, body mass index and HbA1c levels. The CVD-positive group had the significantly lower GIR value than the CVD-negative group (2.06 +/- 0.66 vs. 3.45 +/- 1.75, P < 0.005). The GIR value was also significantly lower in the hypertriglyceridemic group compared with the normotriglyceridemic group (2.50 +/- 1.36 vs. 4.03 +/- 1.82, P < 0.0005). However, there was no significant difference between the hypertensive and normotensive groups and between the high cholesterol or low HDL-cholesterol groups and their respective control groups. In conclusion, these results suggest that IR contributes to the clustering of CVD-RFs which may accelerate the development of CVD in the subgroup of Japanese NIDDM patients.

Adult↗
PubMed1994

Development of proliferative retinopathy in Japanese patients with IDDM: Tokyo Women's Medical College Epidemiologic Study.

We studied the development of proliferative diabetic retinopathy (PDR) in Japanese insulin-dependent diabetes mellitus (IDDM). Subjects were 373 patients who were diagnosed as IDDM between 1951 and 1984, before the age of 30 years, and had no PDR at the first visit to the Diabetes Center. Development of PDR was analyzed by Kaplan-Meier's life-table method in relation to the duration of IDDM. The cumulative incidence of PDR was 20% at 15 years of duration of IDDM, 40% at 19 years, and 70% at 29 years. Female patients (n = 233) developed PDR significantly faster than males (n = 140) (P < 0.002). In both sexes, patients with onset of IDDM at 0-8 years showed significantly slower development than patients with the onset at 9-17 (P < 0.0001) and 18-29 years (P < 0.001). Impact of femaleness on the development was the greatest in patients with age at onset of IDDM at 9-17 years (P < 0.005). Analysis according to the calendar year at onset of IDDM and diabetes duration at the first visit to the Diabetes Center did not show any significant influence on the development of PDR. In conclusion, sex and age at onset of IDDM may be associated with increased risk for the development of PDR in relation to the duration of diabetes in Japanese IDDM.

Adolescent↗