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Biomedical subjects

F Umeda

Publications and source records attributed to F Umeda.

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

Modification of prostaglandin synthesis in washed human platelets and cultured bovine aortic endothelial cells by glycosylated low density lipoprotein.

Glycosylation of low-density lipoprotein (LDL) is known to be increased in diabetic patients. Recent studies have demonstrated that glycosylated (glc-) LDL contributes to the acceleration of atherosclerosis in diabetes. In the present study, we evaluated the effect of glc-LDL prepared in vitro on platelet aggregation and thromboxane B2 (TxB2) production in washed human platelets and on 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) production by cultured bovine aortic endothelial cells. After preincubation of washed platelets with glc-LDL or control LDL, thrombin-induced platelet aggregation and TxB2 production were measured. Control LDL enhanced the platelet aggregation rate and TxB2 production in a time- and dose-dependent manner. Glc-LDL showed significantly greater enhancement of those platelet functions than control LDL. On the other hand, while 6-keto-PGF1 alpha production was stimulated by control LDL in a time- and dose-dependent manner, glc-LDL significantly reduced the stimulatory effect of control LDL on 6-keto-PGF1 alpha production. These results suggest that modification of prostaglandin synthesis in platelets and endothelial cells by glycosylated LDL may lead to platelet hyperaggregation and thrombus formation in diabetes.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Glucose inhibits prostacyclin production by cultured aortic endothelial cells.

A reduction in production of prostacyclin (PGI2) by the cells in the vascular wall may play a role in the pathogenesis of atherosclerosis in diabetic patients. The present study was undertaken to evaluate the effect of glucose on PGI2 production by endothelial cells in vitro. It was shown that PGI2 production by cultured bovine aortic endothelial cells was significantly reduced in the presence of a high concentration of glucose (300 mg/dl) compared with physiological concentrations of glucose (100 mg/dl). In contrast, no reduction in PGI2 production was observed in cells cultured with equimolar mannitol, suggesting that glucose itself, rather than the effect of osmolality, inhibited PGI2 production by cultured endothelial cells. In addition, a high concentration of glucose also inhibited the proliferation of cultured endothelial cells.

Animals↗
PubMed1988

Defective processing of insulin-receptor precursor in cultured lymphocytes from a patient with extreme insulin resistance.

We have studied a patient with extreme insulin resistance, acanthosis nigricans, and decreased erythrocyte insulin binding. EBV-transformed lymphocytes from this patient exhibited markedly reduced binding of 125I-insulin. Radioiodination of cell surface receptors followed by immunoprecipitation with anti-receptor antibodies revealed the presence of increased amounts of a 210-kD protein but no detectable alpha or beta subunits. Continuous labeling with 2-[3H]mannose revealed the synthesis of a 190-kD precursor and a 210-kD protein. The 210-kD protein was phosphorylated in an insulin-dependent manner at high insulin concentrations. These results suggest that in this patient the biosynthesis of 190-kD receptor precursor, its terminal glycosylation, and intracellular transport to the cell surface proceed normally, while proteolytic maturation to alpha and beta subunits does not occur. We postulate that this defect either results from mutation(s) within the insulin-receptor gene, which render the precursor resistant to cleavage, or from a defect in the receptor processing enzyme.

Acanthosis Nigricans↗
PubMed1986

Conjugal transfer of hydrogen-oxidizing ability of Alcaligenes hydrogenophilus to Pseudomonas oxalaticus.

Conjugal transfer of hydrogen-oxidizing ability (Hox) of the hydrogen bacterium Alcaligenes hydrogenophilus was examined. Intraspecific cross of plasmid pHG21-a that encodes hydrogenases that mediate hydrogen oxidation was most frequent at 25 C; the optimal temperature for growth was 30 C. The plasmid could be transferred from A. hydrogenophilus to Pseudomonas oxalaticus OX1 and OX4, and the resulting strains gained the capacity for autotrophic growth with H2 and CO2. Plasmid pHG21-a was maintained in P. oxalaticus OX1 and OX4 as stably as in A. hydrogenophilus.

Alcaligenes↗
PubMed1986

Isolation of hydrogen-oxidation gene from Alcaligenes hydrogenophilus and its expression in Pseudomonas oxalaticus.

A gene bank of a megaplasmid encoding the hydrogen-oxidizing enzyme system (Hox) in Alcaligenes hydrogenophilus was constructed using a broad host range cosmid vector pVK102, and established in Escherichia coli. Hybrid cosmids containing hox genes were identified by transferring the bank into Pseudomonas oxalaticus OX1 and screening colonies for the ability of H2-dependent autotrophic growth. About 800 colonies were formed under autotrophic conditions. One of the Hox+ transconjugants was isolated and its hydrogenases activities were measured. Although soluble hydrogenase was not detected, the Hox+ transconjugant had four times the membrane-bound hydrogenase activity of A. hydrogenophilus.

Alcaligenes↗
PubMed1986

Effect of glibenclamide on pancreatic hormone release from isolated perifused islets of normal and cysteamine-treated rats.

The effect of glibenclamide, a sulfonylurea agent, on islet hormone secretion, particularly on glucagon was studied using isolated perifused pancreatic islets of normal and cysteamine-treated rats. In normal rat islets, glibenclamide enhanced both insulin and somatostatin release in normoglycemic (50 mg/dL) and glucopenic (0 mg/dL) states, as well as under the condition of arginine stimulation. In contrast, glibenclamide stimulated glucagon release only transiently, then suppressed it in a sustaining manner in each state. In the cysteamine-treated islets, as expected, somatostatin concentrations in the perifusate remained unchanged during the infusion of arginine and/or glibenclamide. Under this condition, glibenclamide enhanced insulin release to the same extent as seen in normal islets, and again markedly inhibited glucagon release. These observations indicate that in isolated perifused rat pancreatic islets, glibenclamide suppresses glucagon secretion independently of D cell stimulation. It is concluded that glibenclamide may exert its inhibitory effect directly on A cell rather than through paracrine action of concomitant somatostatin release, and that the suppression of glucagon secretion by glibenclamide may, in part, contribute to the antidiabetogenic effect of this compound.

Animals↗
PubMed1986

Plasma fibronectin and platelet aggregation in diabetes mellitus.

Plasma fibronectin (FN) is a high-molecular weight glycoprotein produced by endothelial cells, fibroblasts, and other mesenchymal cells. Plasma FN levels were measured in non-insulin-dependent diabetics (NIDDM) (n = 42) and compared with age-matched control subjects (n = 20). Plasma FN levels were significantly higher in the NIDDM patients (44.2 +/- 2.2 mg/dl, mean +/- SE) than in the control subjects (31.2 +/- 2.2 mg/dl). In addition, the rate of platelet aggregation was studied in 23 of the 42 NIDDM patients. Interestingly, the plasma FN levels were significantly elevated, particularly in diabetic patients with enhanced platelet aggregation. It is suggested that elevated plasma FN may be closely related to the abnormality of platelet function in diabetics, which leads to diabetic vascular lesions.

Adult↗
PubMed1986

Reduced serum-stimulatory activity on prostacyclin production by cultured aortic endothelial cells in diabetes mellitus.

Reduced prostacyclin (PGI2) production by the vascular wall has been proposed as a possible cause of macro- or microangiopathy in diabetes mellitus. In the present study, we confirmed the stimulatory activity on PGI2 (PSA) production in plasma-derived serum (PDS) by cultured aortic endothelial cells. Furthermore, the abnormality of PSA was examined in diabetic PDS. PSA in PDS from non-insulin-dependent diabetics significantly decreased as compared with that in PDS from age-matched control subjects. There was no difference in PSA in PDS between diabetic patients with and without vascular complications such as retinopathy and nephropathy. In addition, after treatment with dialysis, PSA in diabetic PDS was still not restored to that in normal PDS. These findings suggest that relatively heat-stable (56 degrees C, 30 min) and nondialyzable PGI2 stimulatory substance(s) may decrease in diabetic PDS. It is concluded that a reduction in PDS-stimulated PGI2 production by the vascular wall can play an important role in the pathogenesis of vascular lesions in diabetes mellitus.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Abnormalities of platelet-derived growth factors in insulin-dependent diabetes.

Platelets are involved in homeostasis of the vascular wall at various levels. An important feature of this involvement is the potential for platelet proliferation. Platelets from normal subjects contain platelet-derived growth factor (PDGF), epithelial growth factor (EGF), and transforming growth factor. We have detected the presence of an excessive growth-promoting activity in the heated supernatant fraction derived from the platelets of young, insulin-dependent diabetics. This activity is most pronounced when measured in cultures of smooth muscle cells and fibroblasts. This activity may be further separated into cationic and anionic fractions by ion exchange chromatography of the platelet-rich supernatant. The cationic factor corresponds to PDGF, whereas the anionic factor appears to be identical to EGF. Chronic, intensive insulin therapy normalizes the excessive growth-promoting activity of platelets from diabetics. Further studies are needed to evaluate the differential release of those growth-promoting factors found in platelets of normal subjects and in patients with vascular disease.

Adult↗
PubMed1985

Effect of plasma, serum and platelets from diabetics on DNA synthesis in cultured vascular smooth muscle cells.

Abnormalities in the regulation of proliferation of vascular smooth muscle are believed to be involved in the development of atherosclerosis. This study addresses the question of whether altered levels or activity of circulating factors in diabetes may influence the growth of vascular smooth muscle cells and fibroblasts. Plasma prepared from a group of patients with insulin-dependent diabetes mellitus was less capable of stimulating DNA synthesis in cultured vascular smooth muscle cells and human lung fibroblasts than plasma from control subjects. In contrast a platelet lysate prepared from the same patients caused significantly greater DNA synthesis than did a platelet lysate prepared from the controls. Thus both increased and decreased growth promoting activity exist in diabetes. The end result of these abnormalities may depend on the sensitivity of the target organ and platelet function, but may be related to the increased risk of atherosclerosis amongst the diabetic population.

Animals↗
PubMed1984

Effect of vitamin E on platelet aggregation in diabetes mellitus.

Vitamin E is known to be an inhibitor of platelet prostaglandin production and aggregation. The rate of platelet aggregation induced by adenosine diphosphate was significantly increased in diabetics with proliferative retinopathy and the enhanced production of thromboxane B2, a stable metabolite of thromboxane A2, was demonstrated in those patients. On the other hand, vitamin E in platelets was significantly reduced in diabetics compared with age matched controls. In addition, it was shown that vitamin E content in platelets examined in diabetic and control subjects inversely correlated with both the rate of platelet aggregation and thromboxane B2 production during aggregation. It is suggested that the reduced vitamin E levels in diabetic platelets can contribute to the mechanisms of the enhanced platelet thromboxane production and aggregation which relate to the development of vascular complications.

Blood Platelets↗
PubMed1984

Effect of vitamin E on platelet aggregation in diabetes mellitus.

Vitamin E is known to be an inhibitor of platelet prostaglandin production and aggregation. The rate of platelet aggregation induced by adenosine diphosphate was significantly increased in diabetics with proliferative retinopathy, and the enhanced production of thromboxane B2, a stable metabolite of thromboxane A2, was demonstrated in those patients. On the other hand, vitamin E was significantly reduced in platelets obtained from diabetics as compared to age matched control subjects. In addition, it was shown that vitamin E content in platelets examined in diabetic and control subjects inversely correlated with both the rate of platelet aggregation and thromboxane B2 production during aggregation. It is suggested that the reduced vitamin E levels in diabetic platelets can contribute to the mechanisms of the enhanced platelet thromboxane A2 production and aggregation which lead to the development of vascular complications.

Adenosine Diphosphate↗
PubMed1984

Effect of prostaglandin synthetase inhibitors on platelet aggregation and thromboxane production in diabetes mellitus.

Platelet aggregation is known to be increased in diabetes mellitus, and the enhanced thromboxane production has been shown to be one of the causes of such abnormal platelet function. To investigate which step is activated in diabetic prostaglandin metabolism, three specific inhibitors of prostaglandin synthetases were used in this study, which were mepacrine, indomethacin and imidazole. Platelet aggregation induced by collagen was significantly increased accompanying enhanced thromboxane production in diabetics with proliferative retinopathy compared with age matched controls. Platelet aggregation in diabetics with proliferative retinopathy was less inhibited by the addition of each inhibitor compared with controls. However, there was no difference in inhibitory pattern of platelet aggregation among the three inhibitors. In addition, thromboxane production during aggregation in diabetics with proliferative retinopathy was significantly greater than that in controls by the addition of each inhibitor. Inhibitory patterns of thromboxane production did not differ among the addition of three inhibitors. It is concluded that enhanced thromboxane production resulting in enhanced platelet aggregation would be related to diabetic vascular complications. This abnormal prostaglandin production can be due to the activation of general steps in prostaglandin metabolism in diabetic platelets, not of a specific enzyme.

Adult↗
PubMed1983

Platelets and vascular smooth muscle: abnormalities of phosphodiesterase, aggregation, and cell growth in experimental and human diabetes.

Platelets appear to be involved in both the maintenance of homeostasis and the regulation of proliferation of vascular smooth muscle cells. Anomalies of platelet function may be responsible in part for the pathogenesis of vascular disease in experimental and human diabetes. In a search for an appropriate animal model, we have studied platelet function and the properties of platelet cyclic NCL-PDE in rats with streptozocin-induced diabetes, spontaneous diabetes, and human insulin-dependent diabetes mellitus (IDDM). It appears that opposite abnormalities in both aggregation and phosphodiesterase activity exist in the two animal models. In human IDDM, similar abnormalities to those seen in the BB model were observed. Vascular smooth muscle cells in culture can be used as a model for studies of the effect of circulating growth factors in animals and humans. A growth inhibitory factor was found in plasma and serum from STZ and human IDDM but not BB. In humans we observed increased growth-promoting activity of diabetic platelets, but this phenomenon was absent in both animal models. It remains to be evaluated whether these differences may account for the fact that diabetic rats appear resistant to development of vascular complications. It also remains to be established which animal model is the best choice for studying growth abnormalities in diabetes.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Cyclic nucleotide phosphodiesterase and aggregation in platelets from diabetic rats.

Platelet aggregation and cyclic nucleotide (cNCL) phosphodiesterase (PDE) have been studied in a new strain of insulin-dependent spontaneously diabetic rat (SDR). The rate of aggregation of washed platelets induced by ADP or ionophore A23187 was decreased in SDR as compared to asymptomatic littermates. The activity of soluble cGMP-PDE was increased in SDR, while no significant difference was observed between SDR and control in soluble and particulate cAMP-PDE activities nor in particulates cGMP-PDE activity. Furthermore, a kinetic study of soluble cGMP-PDE in platelets demonstrated that the apparent Km was lower while the Vmax was higher in SDR. Increases were also observed in the activities of particulate cAMP-PDE and cGMP-PDE at low and high substrate concentrations in liver and heart of SDR. These anomalies of platelet aggregation and cNCL-PDE in SDR were partially correctable by insulin. For comparison, a similar study was performed in streptozotocin-induced diabetic rats (STZ). In contrast to SDR, the rate of platelet aggregation induced by ADP was increased in STZ, and the activity of soluble cGMP-PDE in platelets was decreased in STZ. A similar decrease in the activities of cAMP-PDE in liver was also observed in STZ. This study confirms observations concerning the decrease of cGMP-PDE in tissues of STZ diabetic rats. However, since opposite anomalies in PDE activity as well as a platelet function were observed in another model of diabetes (SDR), the significance of these anomalies in the pathophysiology of diabetes requires further investigation.

3',5'-Cyclic-AMP Phosphodiesterases↗