Biomedical subjects

M Oliveira

Publications and source records attributed to M Oliveira.

At least 91 records · Page 5Linked to original sources

PubMed1987

Hexose transport regulation in cultured fibroblasts derived from normal and type II diabetic patients.

The kinetics of saturable and nonsaturable sugar transport were studied in normal and Type II diabetic cultured skin fibroblasts under fast or slowly growing conditions. The Km of hexose transport for fast and slow-growing normal fibroblasts was 1.38 +/- 0.3 and 0.88 +/- 0.12 mM, respectively, while those of the diabetic fibroblasts were 1.57 +/- 0.29 and 0.8 +/- 0.19 mM, respectively. The respective transport Vmax for normal and diabetic fast-growing cells was 13.9 +/- 0.8 and 12.95 +/- 2.4 nmoles 2-DG/mg protein/min. For slowly growing cells of both groups, a transport Vmax of 11.5 +/- 2.4 and 11.3 +/- 1.7 nmoles 2-DG/mg protein/min was obtained. No significant differences were observed in the Km or Vmax of hexose transport under these various growth conditions between normal and diabetic cell cultures. Nonsaturable sugar uptake as determined by L-glucose or cytochalasin B inhibited 2-DG uptake was variable, but no significant differences were observed between the normal and Type II diabetic cells. The activation energies for saturable and nonsaturable sugar uptake were not different among the two donor groups. Insulin stimulation of hexose transport was studied in the presence and absence of dexamethasone (5 X 10(-6) M) at varying insulin concentrations. No difference was observed in the amount of insulin necessary to obtain a maximum stimulatory response (approximately 33 nM insulin in both groups). Also, the insulin concentration required to achieve a one-half maximal response was not significantly different in the donor groups (i.e., 3.53 +/- 0.6 nM for normals and 3.98 +/- 1.1 nM for diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Characteristics of normal and maturity-onset diabetic (type II diabetes) cell cultures: life spans and DNA synthetic capabilities.

The replicative ability of fibroblasts derived from normal and type II diabetic (non-insulin-dependent) donors and their DNA synthetic capabilities in response to serum and insulin (+/- dexamethasone) have been studied. Comparative replicative life spans of the fibroblasts studied using several lots of serum showed no significant differences between the two donor groups with any lot of serum (p greater than 0.05). Insulin (i.e. 700 nM) and serum (10% v/v) stimulation of DNA synthesis in normal and type II diabetic cultures exhibited no differences in responses. The insulin:control ratios of the normal vs. type II diabetic were 1.61 +/- 0.08 vs. 1.81 +/- 0.11, respectively (p greater than 0.05) while the serum:control ratios were 3.55 +/- 0.58 vs. 4.02 +/- 0.54, respectively (p greater than 0.05). Dexamethasone amplification of the insulin-stimulated DNA synthetic response over a range of insulin concentrations (i.e. 1.6-66.6 nM) expressed no differences between the two donor groups. Additionally, calculation of the insulin concentration necessary for the half-maximal response showed no differences between the normal and diabetic groups (3.47 +/- 0.5 vs. 4.44 +/- 0.8 nM, respectively) (p greater than 0.05). The data suggest that there are no general age-related abnormalities inherent to the type II diabetic cultured cell.

Adult↗

PubMed1985

Control of sugar transport in human fibroblasts independent of glucose metabolism or carrier-substrate interaction.

Transport regulation by different metabolizable and nonmetabolizable sugars was studied in human fibroblasts. Sugars were classed as glucose-like (D-mannose, 3-0-methyl-D-glucose, thio-D-glucose, and D-allose) and starvation-like (D-galactose, D-fructose, L-glucose, D-xylose, 6-deoxy-D-glucose and 2-deoxy-D-glucose) based on their competence in curbing glucose starvation enhanced transport. No significant correlation existed between the ability of a sugar to curb hexose transport and the KI of that sugar in inhibiting hexose transport. Independence of the transport curb from glucose metabolism was observed since nonmetabolizable analogs of D-glucose when substituted for D-glucose in the culture medium effected glucose [i.e. 3-0-methyl-D-glucose (3-OMG)] and starvation-like (i.e. 6- and 2-deoxy-D-glucose) effects. The KI of inhibition pf 2-deoxy-D-glucose transport for 3-OMG was 8.5 mM, similar to those obtained for 6-deoxyglucose and 2-deoxyglucose on 2-deoxyglycose transport (7.5 and 3.5 mM, respectively) and on 3-0-methylglucose transport (3.5 and 2.5 mM, respectively). An equimolar mixture of D-glucose and 3-OMG (5.55 mM each) was more effective than 11.1 mM D-glucose or 3-OMG alone in curbing hexose transport or reversing hexose starvation induced increases in transport. The effect of 3-OMG may be independent of glucose metabolism but it is possible that 3-OMG structurally mimics a metabolite of glucose that may interact with intracellular regulators of carrier degradation and or expression.

3-O-Methylglucose↗

PubMed1983

Enhanced insulin stimulation of sugar transport and DNA synthesis by glucocorticoids in cultured human skin fibroblasts.

Glucocorticoids will enhance the growth of cultured human skin fibroblasts in serum-containing medium. In serum-free cultures hydrocortisone (5 X 10(-6) M) will enhance insulin stimulation of sugar transport and DNA synthesis (as measured by thymidine incorporation into trichloroacetic acid-precipitable material). The optimal concentration for the glucocorticoid effect on DNA synthesis was 5 X 10(-8) M for dexamethasone and 5 X 10(-7) M for hydrocortisone. In dexamethasone-treated cells, concentrations of insulin as low as 250 microU/ml (10 ng/ml) were effective in stimulating DNA synthesis. Further, hydrocortisone and dexamethasone (both at 5 X 10(-6) M) exhibited potentiating effects on insulin-stimulated sugar transport. These effects appeared to be mediated via inhibitory actions on the hexose transport system with the preservation of a functional insulin-receptor interaction resulting in insulin stimulation of deoxy-D-glucose transport at physiological insulin concentrations, 250 microU/ml (10 ng/ml). Hydrocortisone also enhanced specific [125I]insulin binding in these cells. The data indicate that the mechanism(s) of glucocorticoid enhancement of two actions of insulin may be different.

Biological Transport, Active↗

PubMed1983

Cardiac thrombosis and thromboembolism in chronic Chagas' heart disease.

A retrospective study of Chagas' heart disease was carried out by a review of 1,345 autopsy reports, with special reference to cardiac thrombus and thromboembolic phenomena. The incidence of cardiac thrombus was higher in cases of heart failure (36%) than in cases of sudden death (15%), higher in heavier hearts, and unrelated to age or sex. The left- and right-sided cardiac chambers were equally affected by thrombus. Endocarditis and blood stasis were considered important factors in the pathogenesis of cardiac thrombus. Thromboembolic phenomena were more common in the systemic circulation but caused relatively more deaths by pulmonary embolism. Fourteen percent of patients with thromboembolic phenomena died from them. Patients with multiple thromboembolic phenomena had a higher risk of death from embolism. Cardiac thrombosis or thromboembolic phenomena, or both, were present in 44% of the cases studied. Prophylactic measures should be taken for these important complications of Chagas' heart disease.

Arterial Occlusive Diseases↗

PubMed1982

Regulation of sugar transport in cultured diploid human skin fibroblasts.

The regulation of hexose transport under glucose-starvation conditions was studied in cultured human skin fibroblasts. Glucose starvation enhanced the transport of 2-DG and 3-0-methyl-D-glucose (3-OMG) but not of L-glucose. Glucose-starvation enhanced transport was inhibited by cytochalasin B (10 microM). The starvation-induced change in 2-DG transport was due to an increase in the Vmax of both the high and low affinity transport sites (2.8- and 2.4-fold, respectively) with no effect on their Kms. The presence of 5.55 mM glucose, fructose, or L-glucose in the medium resulted in transport increases similar to those seen in glucose-starved cells, while the presence of 5.55 mM glucose, mannose, or 3-OMG repressed 2-DG transport. Glucose-starvation enhancement of 2-DG transport was blocked by cycloheximide (20 micrograms/ml) but not by actinomycin D (0.03 microgram/ml) or alpha-amanitin (3.5 microM). Readdition of glucose (5.55 mM) for six hours to glucose-starved cells led to a rapid decrease in hexose transport that could be blocked by cycloheximide but not actinomycin D. Although readdition of 3-OMG to glucose-starved cells had little effect on reversing the transport increases, glucose plus 3-OMG were more effective than glucose alone. Serum containing cultures (10% v/v) of glucose-fed or glucose-starved cells exhibited rapid decreases in 2-DG transport when exposed to glucose-containing serum-free medium. These decreases were prevented by employing glucose-free, serum-free medium. The data indicate that hexose transport regulation in cultured human fibroblasts involves protein synthesis of hexose carriers balanced by interactions of glucose with a regulatory protein(s) and glucose metabolism as they affect the regulation and/or turnover of the carrier molecules.

3-O-Methylglucose↗

PubMed1980

Studies on the effects of in vitro ageing on saturable and nonsaturable sugar uptake in cultured human skin fibroblasts.

The Vmax for saturable (i.e. 2-deoxy-D-glucose) sugar transport in cultured human fibroblasts was found to increase with in vitro ageing when the results were expressed per 10(6) cells. No age-related changes were observed in the Km for 2-deoxy-D-glucose transport or in nonsaturable (i.e. L-glucose) sugar uptake.

Adult↗

PubMed1979