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Biomedical subjects

L B Salans

Publications and source records attributed to L B Salans.

At least 19 recordsLinked to original sources
PubMed1986

Body composition, adipocyte size, free fatty acid concentration, and glucose tolerance in children of diabetic pregnancies.

Previous studies show that children of women who are diabetic during pregnancy are more obese and have a higher prevalence of non-insulin-dependent diabetes mellitus (NIDDM) than children of women who first developed NIDDM greater than 1 yr after the pregnancy (prediabetic mothers) and children of women who have never developed diabetes (nondiabetic mothers). To determine whether lean and obese children of glucose-intolerant pregnancies can be distinguished from similar children of glucose-tolerant pregnancies, we measured body composition, abdominal and gluteal adipocyte size, fasting free fatty acid (FFA), and fasting and stimulated glucose and insulin concentrations during an oral glucose tolerance test in prepubertal children of glucose-intolerant and prediabetic mothers. Each group ranged in adipocity from 6 to 40% body fat. Age, weight, height, and percentage of body fat were similar in the two groups. There were no significant differences in adipocyte size or in glucose, FFA, C-peptide, and insulin concentrations between the groups. The correlation between abdominal adipocyte size and fasting insulin concentration (r = .91 and .18, t = 2.8, P = .01) was stronger in children from glucose-intolerant than from glucose-tolerant pregnancies, respectively. In terms of the parameters we measured, there are no major differences between children of glucose-intolerant and glucose-tolerant pregnancies.

Adipose Tissue↗
PubMed1985

Insulin and atherogenesis: clinical trials.

The possible role of hyperinsulinism in the generation and perpetuation of atherosclerosis is discussed. Although the hypothesis is an important one that merits intensive study, it is premature to approach the question through a clinical trial. Rather, a concerted effort should be made to gain more information through basic research in laboratory animals and clinical investigations in man. This basic information will form the foundation upon which future, sound clinical trials may be undertaken. The general characteristics of a sound clinical trial are also discussed. Topics highlighted include the need to define the question to be asked; the intervention to be used; the outcome to be measured; the patient population to be studied, including the necessity of a control group; the eligibility and exclusion criteria for entrance into a study; and basic study design. Each of these topics requires attention and careful planning before a trial is begun. Issues of randomizing patients into treatment groups, maximizing the likelihood of compliance, and the need for quality control and careful monitoring are also reviewed.

Arteriosclerosis↗
PubMed1984

Insulin-induced translocation of intracellular glucose transporters in the isolated rat adipose cell.

Three techniques have now been used to demonstrate that insulin stimulates glucose transport in isolated rat adipose cells through the translocation of glucose transporters from a large intracellular pool to the plasma membrane. By using a specific D-glucose-inhibitable cytochalasin B-binding assay, most of the basal cell's transporters are found associated with a low-density microsomal membrane fraction. However, although Golgi marker enzyme activities are also enriched in this fraction, their distributions over all fractions do not parallel that of the transporters. In response to insulin, more than half of the intracellular transporters are translocated to the plasma membranes without a corresponding redistribution of marker enzyme activities. Furthermore, although the Kd of the transporters in the plasma membranes remains constant at approximately 100 nM, that of the intracellular transporters decreases from approximately 140 to approximately 100 nM. Nevertheless, transport activity is reconstitutable from, and an affinity-purified rabbit IgG against the purified human erythrocyte transporter cross-reacts with a 45,000-dalton band in, both plasma membranes and the low-density microsomal membrane fraction in proportion to the number of glucose transporters determined by cytochalasin B binding. Thus, intracellular glucose transporters in the rat adipose cell appear to be 1) localized to a unique membrane species, 2) either compartmentalized in two distinguishable pools or processed during their cycling to the plasma membrane in response to insulin, but fully functional and indistinguishable when reconstituted into liposomes, and 3) immunologically similar to the human erythrocyte glucose transporter.

Adipose Tissue↗
PubMed1983

Insulin-stimulated translocation of glucose transporters in the isolated rat adipose cells: characterization of subcellular fractions.

Insulin stimulates glucose transport in rat adipose cells through the translocation of glucose transporters from an intracellular pool to the plasma membrane. A detailed characterization of the morphology, protein composition and marker enzyme content of subcellular fractions of these cells, prepared by differential ultracentrifugation, and of the distribution of glucose transporters among these fractions is now described. Glucose transporters were measured using specific D-glucose-inhibitable [3H]cytochalasin B binding. In the basal state, roughly 90% of the cells' glucose transporters are associated with a low-density microsomal, Golgi marker enzyme-enriched membrane fraction. However, the distributions of glucose transporters and Golgi marker enzyme activities over all fractions are clearly distinct. Incubation of intact cells with insulin increases the number of glucose transporters in the plasma membrane fraction 4-5 fold and correspondingly decreases the intracellular pool, without influencing any other characteristics of the subcellular fractions examined or the estimated total number of glucose transporters (3.7 X 10(6)/cell). Insulin does not influence the Kd of the glucose transporters in the plasma membrane fraction for cytochalasin B binding (98 nM), but lowers that in the intracellular pool (from 141 to 93 nM). The calculated turnover numbers of the glucose transporters in the plasma membrane vesicles from basal and insulin-stimulated cells are similar (15 X 10(3) mol of glucose/min per mol of transporters at 37 degrees C), whereas insulin appears to increase the turnover number in the plasma membrane of intact cells roughly 4-fold. These results suggest that (1) the intracellular pool of glucose transporters may comprise a specialized membrane species, (2) intracellular glucose transporters may undergo conformational changes during their cycling to the plasma membrane in response to insulin, and (3) the translocation of glucose transporters may represent only one component in the mechanism through which insulin regulates glucose transport in the intact cell.

Adipose Tissue↗
PubMed1982

Mechanism of insulin-resistant glucose transport activity in the enlarged adipose cell of the aged, obese rat.

The effects of increasing cell size on glucose transport activity and metabolism and on the concentrations of glucose transport systems in both the plasma and low density microsomal membranes in isolated adipose cells from the aging rat model of obesity have been examined. Glucose transport activity was assessed by measuring l-arabinose transport and the concentration of glucose transport systems estimated by measuring specific d-glucose-inhibitable cytochalasin B-binding. Basal glucose transport activity increases from 0.3 to 1.4 fmol/cell/min with a 10-fold increase in cell size, but remains constant per unit cellular surface area and is accompanied by a constant 5 pmol of glucose transport systems/mg of membrane protein in the plasma membrane fraction. Maximally insulin-stimulated glucose transport activity, on the other hand, remains constant at 2.3 fmol/cell per min with increasing cell size, but markedly decreases per unit cellular surface area and is accompanied by a decrease from 30 pmol of glucose transport systems/mg of plasma membrane protein to the basal level. These diminished effects of insulin on glucose transport activity and the number of glucose transport systems in the plasma membrane fraction in enlarged cells are paralleled by an 80% decrease in the basal number of glucose transport systems/mg of membrane protein in the low density microsomal membrane fraction, the source of those glucose transport systems appearing in the plasma membrane in response to insulin. The effects of cell size on the metabolism of a low concentration of [1-(14)C]glucose (0.56 mM) directly parallel those on glucose transport activity and the concentration of glucose transport systems in the plasma membrane fraction, and are not associated with significant alterations in the cell's sensitivity to insulin. Thus, adipose cellular enlargement is accompanied by the development of a marked "insulin resistance" at the glucose transport level, which may be the consequence of a relative depletion of glucose transport systems in the intracellular pool.

Adipose Tissue↗
PubMed1982

A possible mechanism of insulin resistance in the rat adipose cell with high-fat/low-carbohydrate feeding. Depletion of intracellular glucose transport systems.

The effects of high-fat/low-carbohydrate feeding on glucose transport activity and on the concentrations of glucose transport systems in the plasma and low-density microsomal membranes in isolated rat adipose cells have been examined. Glucose transport activity was assessed by measuring 3-O-methylglucose transport and the concentration of glucose transport systems estimated by measuring specific D-glucose-inhibitable cytochalasin B-binding. Basal glucose transport activity is not significantly influenced by high-fat/low-carbohydrate relative to low-fat/high-carbohydrate feeding and is accompanied by a constant 10 pmol of glucose transport systems/mg of membrane protein in the plasma membrane fraction. In contrast, maximally insulin-stimulated glucose transport activity decreases from 4.72 to 2.29 fmol/cell/min and is accompanied by a decrease from 44 to 26 pmol of glucose transport systems/mg of plasma membrane protein. These diminished effects of insulin on glucose transport activity and the concentration of glucose transport systems in the plasma membrane fraction are paralleled by a 48% decrease in the basal number of glucose transport systems/mg of membrane protein in the low-density microsomal membrane fraction, the source of those glucose transport systems appearing in the plasma membrane in response to insulin. Thus, the "insulin-resistant" glucose transport of the adipose cell with high-fat/low-carbohydrate feeding may be the consequence of a depletion of glucose transport systems in the intracellular pool.

Adipose Tissue↗
PubMed1982

Adipose tissue cellularity in woodchucks: effects of season and captivity at an early age.

The objectives of this study were to determine the roles of adipocyte hypertrophy and hyperplasia in the prehibernatory weight gain of adult woodchucks and in the increased body weight of woodchucks born in captivity. The seasonal increase in weight in wild adult woodchucks was associated with an increase approaching tenfold in both body fat and in subcutaneous and retroperitoneal adipocyte size. There was no increase in total adipocyte number. Four groups of woodchucks were used in the study of the effect of captivity: I) animals born to females bred in the laboratory; II) those born to females captured just before parturition; III) those captured at weaning; and IV) animals captured at 12 months of age. At 14 months non-fat body weight and subcutaneous adipocyte size were equal in the four groups. The males but not the females in Groups I, II, and III had both an increased body fat content and a significantly increased total adipocyte number in comparison to the males in Group IV and the adults in the seasonal study. This study demonstrates that captivity at an early age, unlike prehibernatory weight gain, is associated with an increased adipocyte number in male woodchucks, and this increase can occur after weaning.

Adipose Tissue↗
PubMed1981

Adipose cell size-function relationships: insulin binding and degradation.

125I-insulin binding and degradation have been studied in isolated rat adipose cells of increasing size. Binding at 24 degrees C reaches a steady state by 40-60 min in the absence of significant degradation. At 37 degrees C, binding reaches only a transient maximum by 10-15 min because insulin is rapidly degraded. Cellular enlargement is associated with increasing steady-state binding per cell at 24 degrees C, and increasing maximum binding and degradation per cell at 37 degrees C, in spite of increasing plasma insulin concentrations in the rats from which cells were prepared. Detailed steady-state studies at 24 degrees C, however, fail to delineate the mechanism of these alterations. Although dissociation experiments are consistent with the presence of a small degree of negatively cooperative binding site interaction, its magnitude is unchanged with increasing cell size. Furthermore, binding levels per unit cellular surface at 24 degrees C, at least at those insulin concentrations eliciting a biological response, remain relatively constant. None of the alterations in insulin binding observed here can explain the enlarged adipose cell's markedly decreased metabolic response to insulin.

Adipose Tissue↗
PubMed1981

Effects of dietary composition on glucose metabolism in rat adipose cells.

The effect of altered dietary carbohydrate and fat content on equilibrium insulin binding to, and glucose transport activity and metabolism in, isolated rat epididymal adipose cells has been studied. Alterations in basal and insulin-stimulated total glucose utilization induced by changes in the ratio of dietary carbohydrate to fat are accounted for by specific effects of dietary composition at two levels of cellular function: 1) glucose transport across the cell's plasma membrane, specifically, the number of functional glucose transport systems, and 2) the cell's maximal capacity for glucose metabolism. These effects occur without alterations in insulin binding or the cell's sensitivity to insulin. Furthermore, diet-induced changes in the pattern of 14CO2, and 14C-triglyceride glycerol and fatty acid production appear to be accounted for primarily by the influence of dietary composition on the total amount of glucose entering the cell. Thus, under the conditions of this study, changes in dietary composition alter the adipose cell's capacities for glucose transport and metabolism without altering the mechanisms of insulin action or regulating the metabolic flow of glucose carbons.

Adipose Tissue↗
PubMed1981

A possible mechanism of insulin resistance in the rat adipose cell in streptozotocin-induced diabetes mellitus. Depletion of intracellular glucose transport systems.

The effects of insulin-dependent diabetes mellitus on glucose transport activity and on the concentrations of glucose transport systems in the plasma and low density microsomal membranes in adipose cells isolated from streptozotocin-induced diabetic rats have been examined. Glucose transport activity was assessed by measuring 3-O-methylglucose transport and the concentration of glucose transport systems estimated by measuring specific D-glucose-inhibitable cytochalasin B-binding. Basal glucose transport activity decreases from 0.19 to 0.12 fmol/cell per min with the induction of diabetes, but remains constant per unit cellular surface area and is accompanied by a constant 6 pmol of glucose transport systems/mg of membrane protein in the plasma membrane fraction. Maximally insulin-stimulated glucose transport activity decreases from 3.16 to 1.05 fmol/cell per min and from 0.26 to 0.12 amol/micrometers 2 per min, and is accompanied by a decrease from 25 to 15 pmol of glucose transport systems/mg of plasma membrane protein. These diminished effects of insulin on glucose transport activity and the concentration of glucose transport systems in the plasma membrane fraction are paralleled by a 45% decrease in the basal number of glucose transport systems per milligram of membrane protein in the low density microsomal membrane fraction, the source of those glucose transport systems appearing in the plasma membrane in response to insulin. Thus, the "insulin resistant" glucose transport of the adipose cell in the streptozotocin-induced diabetic rat appears to be the consequence of a depletion of glucose transport systems in the intracellular pool.

Adipose Tissue↗
PubMed1980

Intracellular glucose concentration in small and large rat adipose cells.

Intracellular free glucose concentrations have been estimated in small and large isolated epididymal adipose cells prepared from young lean and older obese rats using glucose-induced steady-state tracer 3-O-methylglucose countertransport. Steady-state 3-O-methylglucose uptake was measured in the presence of 2--50 mM glucose or sucrose in the absence or presence of 100 microU insulin/ml. The ratio of the uptake of 3-O-methylglucose in the presence of glucose to that in the presence of sucrose at each sugar concentration was then utilized to estimate the corresponding intracellular glucose concentration. At all three extracellular glucose concentrations tested in the absence of insulin, intracellular concentrations of glucose are greater in the large cells than in the small cells. In the presence of 2 mM glucose and insulin, on the other hand, intracellular glucose concentrations of 2 mM are attained, regardless of cell size. These results suggest that transport may not be the rate-limiting step for glucose metabolism at physiologic glucose concentrations either in the enlarged adipose cell in the absence or presence of insulin or in the small adipose cell in the presence of maximally stimulating concentrations of insulin.

Adipose Tissue↗