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F Umeda

Publications and source records attributed to F Umeda.

At least 19 recordsLinked to original sources
PubMed1992

Vitamin E binds to specific binding sites and enhances prostacyclin production by cultured aortic endothelial cells.

We evaluated the effect of d-alpha-tocopherol (vitamin E) on the production of prostacyclin (PGI2) by cultured bovine aortic endothelial cells. Vitamin E at physiological doses significantly enhanced the production of PGI2 by aortic endothelial cells when added to the culture simultaneously with histamine, the Ca2+ ionophore A23187 (A23187), plasma-derived serum (PDS), or arachidonic acid. This effect was found to occur in a time- and dose-dependent manner, and the maximal enhancement was produced by 9.28 microM of vitamin E for 1 h incubations. Significantly lower amounts of lipid peroxides were measured in endothelial cells stimulated by 10% PDS with 9.28 microM of vitamin E than in those stimulated without vitamin E for over 24 h, although the stimulation during the initial 1 to 12 h period did not have a significant effect on lipid peroxide formation in cultured aortic endothelial cells. We also demonstrated that bovine aortic endothelial cells have specific binding sites for [3H]vitamin E that exhibited time- and temperature-dependent saturability. At 4 degrees C, the nonspecific binding was 8-12% of the total binding, and the specific binding reached equilibrium by 2 h. Specific binding increased with the concentration of [3H]vitamin E and became saturated at concentrations between 1.5 microM and 2.0 microM per 2.0 x 10(5) cells. Raising the unlabeled vitamin E concentration from 97.7 nM to 1,000 microM reduced the specific binding of 2.0 microM [3H]vitamin E.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Vitamin E restores reduced prostacyclin synthesis in aortic endothelial cells cultured with a high concentration of glucose.

Reduced prostacyclin (PGI2) production by the vascular wall may play an important role in the pathogenesis of vascular lesions such as atherosclerosis. The present study was undertaken to evaluate the effect of vitamin E on the production of PGI2 and other prostaglandins (prostaglandin E2 [PGE2], thromboxane A2 [TXA2], and 15-hydroxyeicosatetraenoic acid [15-HETE]) by bovine aortic endothelial cells cultured in a high concentration of glucose (300 mg/dL). Compared with endothelial cells cultured in 100 mg/dL glucose, the production of PGI2 and other prostaglandins, except 15-HETE, was significantly reduced in cultures containing 300 mg/dL glucose when stimulated by histamine, the Ca2+ ionophore, A23187, or human plasma-derived serum (PDS). The addition of vitamin E to each stimulant significantly restored the production of PGI2, PGE2, and TXA2, products of the cyclo-oxygenase pathway, in aortic endothelial cells cultured in 300 mg/dL glucose. This effect of vitamin E on the stimulation of prostaglandin production was generally specific for D-alpha-tocopherol, but not for the other vitamin E analogs tested. However, vitamin E and the stimulants had no effect on the production of 15-HETE, a product of the lipoxygenase pathway. Moreover, vitamin E alone, without stimulants, did not affect prostaglandin production in cultured bovine aortic endothelial cells. These results suggest that vitamin E may restore reduced PGI2, PGE2, or TXA2 production by bovine aortic endothelial cells cultured in a high concentration of glucose. It seems likely that vitamin E may restore depressed PGI2 production by the vascular wall in hyperglycemic conditions such as those seen in patients with diabetes mellitus.

Animals↗
PubMed1992

Release of amylin from perfused rat pancreas in response to glucose and glucagon.

The effects of glucose and glucagon on the release of amylin from the isolated perfused rat pancreas were studied. Amylin is a 37-amino acid peptide isolated from pancreatic islet amyloid of patients with non-insulin-dependent diabetes mellitus (NIDDM). Glucose dose-dependently stimulated a biphasic release of amylin from the pancreas in parallel with that of insulin. However, the release of amylin induced by high concentrations of glucose was partially dissociated from that of insulin. The amylin-insulin molar ratios induced by 22.2 mM and 33.3 mM glucose (1.11 +/- 0.05%, 1.05 +/- 0.04%, respectively) were significantly higher than that induced by 16.7 mM glucose (0.90 +/- 0.04%, P less than 0.01 vs 22.2 mM glucose, P less than 0.05 vs 33.3 mM glucose). In the presence of 5.6 mM glucose, glucagon also stimulated the release of amylin from the perfused pancreas in parallel with that of insulin. These findings suggest that amylin may be a secretory protein from the pancreas and that the concomitant secretion of amylin and insulin might contribute to glucose homeostasis.

Amyloid↗
PubMed1992

Partial purification of serum prostacyclin stimulatory activity by heparin-agarose column; abnormality detected in diabetics.

Human plasma-derived serum (PDS) stimulated the production of 6-keto-PGF1 alpha (a stable metabolite of PGI2) by cultured bovine aortic endothelial cells. The stimulation was both time- and dose-dependent. The main prostacyclin stimulatory activity (PSA) in human PDS remained biologically active after dialysis and was inhibited by the simultaneous addition of heparin. The maximum inhibition of PSA was obtained with 10 micrograms/ml heparin. PDS obtained from patients with non-insulin-dependent diabetes mellitus (NIDDM, n = 24) showed significantly less PSA than that from the control subjects (n = 11). A decrease in PSA was also found in diabetic patients using dialyzed PDS. The PSA in human PDS had a specific binding affinity to heparin-agarose and the bound PSA was eluted by a linear gradient of NaCl, which showed two major PSA peaks at 1.0 and 1.5 M NaCl. The dialyzed, mixed PDS from patients with NIDDM and the control subjects was independently applied to a heparin-agarose column and eluted by a linear gradient of NaCl. Comparing the PSA in each peak between the diabetic and the control dialyzed PDS, the PSA at 1.5 M NaCl was markedly decreased in the diabetic patients, but the PSA at 1.0 M NaCl did not change significantly. These observations suggest that the decreased PSA in human diabetic PDS may result mainly from the decrease in the activity of a specific non-dialyzed factor(s) which can bind to heparin. The decreased PSA in serum seems to be responsible in part for decreased PGI2 synthesis by the vascular wall of diabetics.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Effects of exogenous somatostatin and insulin on islet amyloid polypeptide (amylin) release from perfused rat pancreas.

This study examined the effects of exogenous somatostatin and insulin on the release of islet amyloid polypeptide (IAPP), or amylin, from the isolated perfused rat pancreas. Somatostatin inhibited the release of both amylin and insulin from the perfused pancreas to the same extent. The infusion of 10 nM somatostatin resulted in 40% inhibition of the secretion of both amylin and insulin induced by 11.1 mM glucose and 10 mM arginine, and this inhibition was significantly increased to 70% by the infusion of 100 nM somatostatin (p less than 0.05). The amylin/insulin molar ratios remained constant at 0.8% and were not changed by the infusion of somatostatin. On the other hand exogenous insulin at a concentration of 1.8 nM did not affect the release of amylin induced by 11.1 mM glucose and 10 mM arginine, whereas 180 nM insulin slightly, although not significantly, inhibited the release of amylin by 15%. These findings suggest that the release of amylin may be negatively regulated by somatostatin and that circulating insulin may have no direct effect on the release of amylin at least at a physiological concentration.

Amyloid↗
PubMed1992

Nucleotide sequences of membrane-bound hydrogenase gene in Alcaligenes hydrogenophilus.

The nucleotide sequences of membrane-bound hydrogenase small (hupS) and large (hupL) subunit genes of hydrogen bacterium Alcaligenes hydrogenophilus were determined. The hupS and hupL genes encoded polypeptides of 363 and 619 amino acids, respectively. The hupS was located upstream of hupL with 35bp of intergenic region. The consensus ribosome-binding sequences were identified upstream of the start codons of hupS and hupL. Amino acid sequence of hupS is very similar to that of Rhodobacter capsulatus, Bradyrhizobium japonicum, and Azotobacter vinelandii at amino acid levels of 82%, 77%, and 81%, respectively. Similarly, amino acid sequence of HupL is similar to that of R. capsulatus, B. japonicum, and A. vinelandii at amino acid levels of 63%, 65%, and 68%, respectively. Northern hybridization analysis showed that hupS and hupL were co-transcribed, and addition of fructose to the culture medium remarkably decreased the amount of mRNA transcribed from hupS and hupL.

Alcaligenes↗
PubMed1992

Effect of glucose on Na, K-ATPase activity in cultured bovine aortic endothelial cells.

The effect of high concentrations of glucose on Na, K-ATPase activity and the polyol pathway was studied using cultured bovine aortic endothelial cells. Na, K-ATPase activity was expressed as ouabain-sensitive K+ uptake. A significant decrease in Na, K-ATPase activity with an intracellular accumulation of sorbitol was found in confluent endothelial cells incubated with 400 mg/dl glucose for 96 h. However, there was no significant change in the Na, K-ATPase activity or sorbitol content of the cells incubated with 100 mg/dl glucose plus 300 mg/dl mannitol. The decrease in Na, K-ATPase induced by the high glucose concentration was restored by the simultaneous addition of 10(-4) M ponalrestat (ICI 128,436; Statil), an aldose reductase inhibitor. The addition of this agent also significantly reduced the increase in sorbitol induced by high glucose levels. These results suggest that the decrease in Na, K-ATPase activity induced in cultured aortic endothelial cells by high concentrations of glucose may be caused in part by the accumulation of sorbitol.

Aldehyde Reductase↗
PubMed1992

Type A-insulin resistance with lipopexia on extremities: a case report.

We present the unusual case of a 17-year-old female with insulin-resistant diabetes, acanthosis nigricans, hirsutism, amenorrhea, dental dysplasia and lipopexia on the extremities. She had been diagnosed as having border line diabetes with hyperinsulinemia at age 12 when she was not obese and diabetes mellitus at age 13. On admission, she was obese and had lipopexia only on the extremities. The presence of hyperinsulinemia and poor response to exogenous insulin suggested severe insulin resistance. Insulin binding to transformed B-lymphoblasts derived from her was extremely low compared to the normal control, showing decreased receptor affinity. Her parents and sister exhibited hypersecretion of insulin in response to a 75 g oral glucose tolerance test. Her mother was diabetic, and her father and sister had border line diabetes, whereas her brother had a normal response. These findings support strongly the diagnosis of a type A syndrome with severe insulin resistance associated with lipopexia on the extremities. A genetic defect in the insulin receptor gene may be responsible.

Absorptiometry, Photon↗
PubMed1992

Effect of pravastatin on serum lipids, apolipoproteins and lipoprotein (a) in patients with non-insulin dependent diabetes mellitus.

In 43 patients with non-insulin dependent diabetes mellitus (NIDDM) associated with hypercholesterolemia, the effect of pravastatin, a potent HMG CoA-reductase inhibitor, on serum lipids, apolipoproteins and lipoprotein (a) was examined. After 1 to 3 months administration of 10 mg per day of pravastatin, the serum levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) were significantly decreased, while the serum level of high density lipoprotein cholesterol (HDL-C) was significantly increased in patients with NIDDM. The levels of apolipoproteins B (apo B) and E were significantly decreased, while apolipoprotein AI (apo A-I) was not changed by the administration of pravastatin. The atherogenic indices (LDL-C/HDL-C and apo B/apo A-I) were significantly decreased by the administration of this drug. The serum lipoprotein (a), which was increased in the diabetic patients, was not affected by the pravastatin treatment. Plasma glucose and hemoglobin A1c levels were not affected by the treatment. We concluded that pravastatin is a potentially useful agent in the treatment of hypercholesterolemia in patients with NIDDM.

Apolipoproteins↗
PubMed1992

Relative hypersecretion of amylin to insulin from rat pancreas after neonatal STZ treatment.

With isolated perfused pancreases from normal and diabetic model rats, we studied alterations of the secretion of islet amyloid polypeptide, or amylin, which has been recently identified as a major component of amyloid deposits in the pancreatic islets of patients with non-insulin-dependent diabetes mellitus. Neonatal (n) Wistar-King albino rats given streptozocin (STZ) on the 2nd (n2STZ) or 5th (n5STZ) neonatal day exhibited moderate and marked elevations, respectively, of plasma glucose and HbA1 as adults compared with control rats given the vehicle. The release of amylin from the perfused pancreases in response to glucose and arginine paralleled that of insulin in all three groups. However, the molar ratio of secreted amylin to insulin in response to 16.7 mM glucose by n5STZ pancreases (6.55 +/- 0.71%) was significantly greater than that for either n2STZ (1.71 +/- 0.24%, P less than 0.05) or the control (0.60 +/- 0.03%, P less than 0.05) pancreases. The secreted amylin-insulin ratio of n2STZ pancreases also was significantly greater than that of the controls (P less than 0.05). The increased amylin-insulin molar ratios of both n2STZ and n5STZ pancreases also occurred during infusions of 33.3 mM glucose and 10 mM arginine. These findings suggest that amylin secretion may be preserved in diabetic rats with reduced beta-cell mass and that hyperglycemia may increase amylin production independently of that of insulin, which may be significant in the pathogenesis of non-insulin-dependent diabetes mellitus.

Amyloid↗
PubMed1992

Alterations in femoral bone histomorphometry and vitamin D metabolism in neonatal streptozotocin-induced diabetic rat.

Histomorphometric examination and histological observation of femoral bone were performed on long-standing neonatal streptozotocin-induced diabetic rats (n2STZ, n5STZ) as a human model of non-insulin-dependent diabetes mellitus. The growth and strength of femurs decreased in the STZ diabetic rats. Histomorphometric parameters such as cortical bone thickness, number of metaphysical trabeculae and percent trabecular volume of metaphysical area all significantly decreased in the STZ diabetic rats. There were no significant differences in parameters between the n2STZ and n5STZ diabetic rats. Histological findings demonstrated no significant change in the number of osteoclasts in femur nor change corresponding to osteomalacia. Bone absorption in the STZ diabetic rats appeared unchanged. The plasma calcium level did not change in the STZ diabetic rats, although their plasma phosphate or A1-p levels increased. Circulating 24, 25 (OH)2D3 was significantly lower in the STZ diabetic rats than the controls. However, 25 (OH) D3 or biologically active 1, 25 (OH)2D3 was not different between the controls and STZ diabetic rats. Osteopenia is thus present in the femurs of long-standing neonatal STZ diabetic rats, due in part to abnormal vitamin D metabolism.

Animals↗
PubMed1992

Utility of the latex agglutination nephelometric immunoassay (Albusure Test) in screening for microalbuminuria in patients with diabetes mellitus.

All diabetic patients should be screened for early signs of diabetic nephropathy, because it is a prognostic factor in the disease. The albusure test (AT), a latex agglutination nephelometric immunoassay, is a rapid and low cost test for the detection of microalbuminuria of 30 mg/L or more. We compared the results of AT and of radioimmunoassay (RIA) for urinary albumin to evaluate the clinical utility of AT using fresh urine samples from 74 diabetic patients without persistent proteinuria and from 11 healthy subjects. Urinary albumin levels were 6.0 +/- 2.3 mg/L in the healthy subjects, 11.0 +/- 8.7 mg/L in the AT-negative group (n = 61), and 38.1 +/- 10.2 mg/L in the AT-positive group (n = 13). Using a cut-off value of 30 mg/L by RIA, the rate of coincidence between AT and RIA was 89.2%, although five subjects were false-positive by AT, and three were false-negative. These results show that AT may provide a useful monitor for microalbuminuria, a reliable early marker of diabetic nephropathy.

Adult↗
PubMed1992

[A case of the diabetic nephropathy without hyperglycemia].

We report a case of diabetic nephropathy with impaired glucose tolerance. A 52 year obese woman with nephrotic syndrome and hypertension showed severe and remarkable edema, as her legs were elephantiasis. To be clear the etiology of nephrotic syndrome, we performed renal biopsy. The histological findings of the specimen showed glomerulosclerosis. Additionally the examination of ocular fundus revealed microaneurysm and avascular area. We concluded that diagnosis of this case must be non-insulin-dependent diabetes mellitus.

Diabetes Mellitus, Type 2↗
PubMed1992

Platelet-derived growth factor and growth-promoting activity in the serum samples and platelets of patients with non-insulin-dependent diabetes mellitus.

Although platelet-derived growth factor (PDGF) is thought to be a major mediator of atherosclerotic disease, the pathophysiology of diabetic vasculopathy, including atherosclerosis, is unclear. By means of an enzyme immunoassay that used a monoclonal antibody against human PDGF-B chain, PDGF-like immunoreactivity was determined in serum, platelet-poor plasma, and platelet lysate of 28 patients with non-insulin-dependent diabetes mellitus and 11 control subjects. Growth-promoting activity was also measured by tritiated thymidine incorporation into DNA of cultured human fibroblasts. The PDGF-like immunoreactivity in serum was correlated (r = 0.42; p less than 0.01) with that in platelet lysate prepared from a fixed volume of blood. Furthermore, a correlation (r = 0.70; p less than 0.001) was found between the PDGF-like immunoreactivity and the growth-promoting activity in platelet lysate but not in serum. There was no significant difference between patients with diabetes and control subjects with respect to the PDGF-like immunoreactivity in serum or in platelet lysate (38.2 +/- 2.2 vs 42.8 +/- 3.1 ng/ml or 49.1 +/- 2.4 vs 56.2 +/- 3.4 ng/mg protein; mean +/- SEM). In contrast, the serum growth-promoting activity was lower (p less than 0.05) in patients with diabetes than in control subjects (88.1% +/- 7.1% vs 117.4% +/- 6.9%) and there was a negative correlation (r = -0.39; p less than 0.05) between the serum growth-promoting activity and the fasting plasma glucose level. The growth-promoting activity in platelet lysate of patients with diabetes did not differ from that of the control subjects (59.9% +/- 11.6% vs 65.9% +/- 11.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1991

Increased intracellular calcium mobilization in platelets from patients with type 2 (non-insulin-dependent) diabetes mellitus.

Enhanced platelet functions have been reported in patients with diabetes mellitus. Our recent study demonstrated that phosphoinositide turnover is increased in platelets from diabetic patients. In the present study, we evaluated the abnormality in platelet intracellular calcium mobilization in patients with Type 2 (non-insulin-dependent) diabetes mellitus using fura-2, a fluorescent calcium indicator. Washed platelets were prepared from six diabetic patients with increased platelet aggregation rates (DM-A group), seven diabetic patients with normal platelet aggregation rates (DM-B group), and eight age-matched healthy control subjects. The basal intracellular free calcium concentrations in platelets were similar among the three groups. Thrombin (0.025-0.1 U/ml) induced a dose-dependent increase in intracellular calcium in both the presence and the absence of extracellular calcium. This increase in the presence of extracellular calcium, which depends on calcium influx and release, was significantly higher in the DM-A group than in the DM-B and control groups. However, there was no significant difference between the control group and the DM-B group. In the absence of extracellular calcium, thrombin-induced calcium increase, which depends only on calcium release, was also significantly enhanced in the DM-A group. Furthermore, the calcium increase stimulated by platelet-activating factor (10 nmol/l) with and without extracellular calcium was significantly higher in the DM-A group than in the other groups. Additionally, calcium ionophore A23187 (100 nmol/l) caused a significantly higher calcium increase in the DM-A group with extracellular calcium, while the calcium increase without extracellular calcium showed no significant difference among the three groups. These observations suggest that enhanced intracellular calcium mobilization due to increased calcium influx and release may be closely related to platelet hyperfunctions in diabetes mellitus.

Analysis of Variance↗
PubMed1991

Increased inositol phosphate accumulation in platelets from patients with NIDDM.

We evaluated thrombin-induced inositol phosphate accumulation in [3H]inositol-labeled platelets prepared from patients with non-insulin-dependent diabetes mellitus. There were no significant differences in [3H]inositol incorporation into and contents of phosphoinositides between the diabetic patients and their age-matched control subjects. Thrombin induced a dose- and time-dependent accumulation of inositol phosphate. The accumulation of [3H]inositol trisphosphate and [3H]inositol bisphosphate by thrombin stimulation were significantly enhanced in platelets from the diabetic patients, although the accumulation of [3H]inositol monophosphate did not differ between the diabetic patients and the control subjects. In addition, the platelet aggregation rate induced by thrombin was also significantly enhanced in the diabetic patients in correlation with the enhanced inositol phosphate accumulation. These results suggest that increased inositol phosphate accumulation may cause accelerated platelet functions in diabetes mellitus.

Blood Platelets↗
PubMed1991

A case of insulin allergy: the crystalline human insulin may mask its antigenicity.

We report an unusual case of insulin allergy. A 48-year-old man with non-insulin-dependent diabetes mellitus receiving biosynthetic isophane human insulin (Humulin N) developed itchy wheal-and-flare reactions at the sites of injection. When Humulin N was changed to a semi-synthetic crystalline human insulin zinc (Novolin U), the allergic reactions completely disappeared. Evaluation of his serum showed a high level of insulin-specific IgE. Skin testing with all commercially available insulins showed immediate local reactions to all agents tested except for Novolin U. In addition, decrystallized Novolin U prepared by lowering the pH with acetic acid also induced a positive reaction. These observations suggest that the crystallized structure of human insulin may mask its antigenicity for allergic reactions.

Diabetes Mellitus, Type 2↗