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W Fujimoto

Publications and source records attributed to W Fujimoto.

45 records · Page 3Linked to original sources
PubMed1984

Effects on glucose-induced insulin secretion of lipoxygenase-derived metabolites of arachidonic acid.

Our previous data suggested that lipoxygenation of endogenously released arachidonic acid (AA) is a critical step in stimulus-secretion coupling in the pancreatic beta cell. In the current study using monolayer cultures of neonatal rat islet cells, exogenous arachidonic acid (AA) (5 micrograms/ml) potently stimulated insulin release in the presence of a substimulatory glucose concentration, and potentiated release induced by glucose. Since the latter stimulatory effect of AA is prevented by inhibitors of the lipoxygenase pathway, we examined the effects of various lipoxygenase pathway products on glucose-induced insulin secretion. The mediator was not one of the stable end-products of either limb of the lipoxygenase pathway: 12- or 5-hydroxyeicosatetraenoic acid (HETE) (0.5-2000 ng/ml) did not alter insulin release, whereas 11-HETE, 15-HETE, leukotriene (LT)B4 and the delta 6 trans isomers of LTB4, LTC4 and 11-trans LTC4 all inhibited insulin release. Furthermore, diethylcarbamazine, a selective leukotriene synthesis inhibitor, did not prevent AA- or glucose-induced insulin release, arguing against a role for LTs as the mediator of AA's stimulatory effect. However, the unstable intermediate 12-hydroperoxyeicosatetraenoic acid (12-HPETE), and positional isomers of 12-HPETE, potentiated glucose-induced insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1983

Lipoxygenase pathway in islet endocrine cells. Oxidative metabolism of arachidonic acid promotes insulin release.

Metabolism of arachidonic acid (AA) via the cyclooxygenase pathway reduces glucose-stimulated insulin release. However, metabolism of AA by the lipoxygenase pathway and the consequent effects on insulin secretion have not been simultaneously assessed in the endocrine islet. Both dispersed endocrine cell-enriched pancreatic cells of the neonatal rat, as well as intact islets of the adult rat, metabolized [(3)H]AA not only to cyclooxygenase products (prostaglandins E(2), F(2alpha), and prostacyclin) but also to the lipoxygenase product 12-hydroxyeicosatetraenoic acid (12-HETE). 12-HETE was identified by coelution with authentic tritiated or unlabeled 12-HETE using four high performance liquid chromatographic systems under eight mobile-phase conditions and its identity was confirmed by gas chromatography/mass spectrometry using selected ion monitoring. The predominant effect of exogenous AA (5 mug/ml) was to stimulate insulin release from pancreatic cells grown in monolayer. This effect was concentration- and time-dependent, and reversible. The effect of AA upon insulin release was potentiated by a cyclooxygenase inhibitor (indomethacin) and was prevented by either of two lipoxygenase inhibitors (5,8,11,14-eicosatetraynoic acid [ETYA] and BW755c). In addition, glucose, as well as two structurally dissimilar agents (the calcium ionophore A23187 and bradykinin), which activate phospholipase(s) and thereby release endogenous AA in several cell systems, also stimulated insulin secretion. The effects of glucose, glucagon, bradykinin and high concentrations of A23187 (5 mug/ml) to augment insulin release were blocked or considerably reduced by lipoxygenase inhibitors. However, a lower concentration of the ionophore (0.25 mug/ml), which did not appear to activate phospholipase, was resistant to blockade. Exogenous 12-HETE (up to 2,000 ng/ml) did not alter glucose-induced insulin release. However, the labile intermediate 12-hydroperoxy-ETE increased insulin release. Furthermore, diethylmaleate (which binds intracellular glutathione and thereby impedes conversion of the lipoxygenase intermediates hydroperoxy-ETE and leukotriene A(4) to HETE and leukotriene C(4), respectively) potentiated the effect of glucose and of exogenous AA. Finally, 5,6-epoxy, 8,11,14-eicosatrienoic acid (a relatively stable epoxide analogue of leukotriene A(4)) as well as two other epoxy-analogues, potentiated glucose-induced insulin release. We conclude that dual pathways of AA metabolism exist in islet endocrine cells and have opposing regulatory effects on the beta cell-an inhibitory cyclooxygenase cascade and a stimulatory lipoxygenase cascade. Labile products of the latter pathway may play a pivotal role in stimulus-secretion coupling in the islet.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1981

[Use of cefroxadine dry syrup in the management of acute skin infections in children (author's transl)].

1. Cefroxadine dry syrup was in principle administered at the dosage of 10 mg per kilogram of body weight 3 times a day. 2. Evaluation was done in 4 grades, i.e. excellent, good, fair and poor. 3. According to subjective judgement by attending doctors, 'excellent' or 'good' was recorded in 90.7%. 4. If the evaluation was partially standardized, 'excellent' or 'good' was obtained in 74.8% of total 163 cases and in 78.7% of 108 impetigo cases. 5. Side effects were observed in 3 cases (diarrhea 1, fever 2). No direct correlation of these complaints with the administration of the present drug was confirmed.

Abscess↗
PubMed1977

Two cholesterol ester hydrolases. Distribution in rat tissues and in cultured human fibroblasts and monkey arterial smooth muscle cells.

Hydrolytic activity against acetone-dispersed [4-14C]cholesterol oleate has been assayed as a function of pH in seven parenchymal tissues, blood cells, and plasma of the rat, as well as in cultured human fibroblasts and monkey (Macaca nemestrina) arterial smooth muscle cells. Both acid and neutral hydrolytic activities were present in all of these except rat plasma. The pH optima were in all cases close to pH 4.5 and pH 6.8. Acid activity was quite constant from tissue to tissue, while neutral activity varied greatly, being greatest in adrenal, testis, and adipose tissue. Subcellular fractionation of human fibroblasts allowed demonstration that activities at pH 4.5 and pH 6.8 were concentrated in different fractions, apparently lysosomal and polysomal, respectively. It appears most cell types, including fibroblasts and smooth muscle cells, contain two separate enzymes capable of hydrolyzing cholesterol esters. The neutral pH polysomal enzyme, which is especially prominent in certain tissues, may have a function related to the specialized roles of these tissues.

Animals↗
PubMedDate not supplied

Insulin and glucose: relationships with hassles, anger, and hostility in nondiabetic older adults.

Relationships of psychosocial factors (anger, hostility, hassles, and caregiving) with fasting insulin and glucose levels were examined. Samples included two groups of nondiabetic adults (mean age = 69.4 years): spouse caregivers (CG) of individuals with diagnoses of Alzheimer's disease (AD) (N = 78) and spouses of nondemented controls (CO) (N = 72) matched for age and gender. The groups were assessed twice with a 15-to 18-month hiatus. To obtain more stable assessments, all biopsychosocial measures were averaged over time. Psychosocial factors were associated with insulin and glucose, even after controlling for significant health variables: obesity, lipids, and cardiovascular disease. As hypothesized, CG with high anger-out/hostility (AOHO) had significantly higher glucose levels than all other group combinations. The glucose levels for subjects with high hassles or high AOHO were significantly higher than those for subjects who were low on both of these factors. For insulin, a three-way interaction occurred among AOHO, hassles, and gender-hormone replacement therapy (HRT); in women taking HRT, no relationships occurred between insulin with AOHO and hassles. In women not taking HRT, those with high AOHO and high hassles had significantly higher insulin levels than the other three combinations, whereas in men, those with either high AOHO or high hassles had significantly higher insulin levels than men who were low on both of these factors. Given these results, future research should examine the degree to which interactions between metabolic processes with psychosocial variables, gender, and HRT have long term health consequences in nondiabetics.

Aged↗
PubMedDate not supplied

Expression of the bcl-2 family of genes in the course of keratinocyte differentiation.

Bcl-2 and its homologous proteins play an important role in the control of apoptosis, mainly at the level of mitochondria. Their relationship to differentiation as well as regulation by retinoids in certain cell types has been recently reported. We examined the expression of the bcl-2 family oncoproteins bax, bak, bcl-2, bcl-xL, and mcl-1 in the course of differentiation of human keratinocytes cultured at low- (0.15 mM) and high- (1.87 mM) calcium concentrations. The pro-apoptotic bax showed an increase in expression during the first six days of culture, whereas bak remained stable until day 10 when it increased only slightly in both low- and high-calcium treated cells. The expression of anti-apoptotic bcl-xL increased during the first four days of culture, with a more pronounced increase in low- than in high-calcium treated keratinocytes. Apoptosis-suppressing bcl-2 and mcl-1 proteins did not change significantly in our culture experiment. None of the examined proteins of the bcl-2 family appeared altered upon addition of all-trans retinoic acid (10(-6) M) to the culture medium. We compare the results of our in vitro study with the expression of the bcl-2 family proteins in normal epidermis.

Blotting, Western↗
PubMedDate not supplied

The NHLBI workshop on Hypertension in Hispanic Americans, Native Americans, and Asian/Pacific Islander Americans.

In June 1994, the National Heart, Lung, and Blood Institute held a workshop entitled "Epidemiology of Hypertension in Hispanic Americans, Native Americans, and Asian/Pacific Islander Americans." The studies that served as the basis for the workshop along with a summary of two workshop panel discussions are being published as a supplement by Public Health Reports. In this article, the authors present graphs that compare results across these studies with data for non-Hispanic whites, blacks, and Hispanics from the Third National Health and Nutrition Examination Survey. The graphs indicate differences in mean blood pressure levels within and among these three population groups; such differences are also apparent in comparisons of these groups with the U.S. white and black populations. Although they appear modest, these differences are sufficient to result in increased mortality rates in populations with higher levels of hypertension. Environmental influences appear to underlie most of these differences. In all of these populations, blood pressure control rates are poor. Based on these studies, hypertension prevention and control programs should be undertaken. Special emphasis should be placed on the underserved minority populations that were the focus of the workshop.

Adult↗