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Biomedical subjects

U Smith

Publications and source records attributed to U Smith.

At least 145 records · Page 8Linked to original sources
PubMed1987

Glucose tolerance in hypertensive patients during treatment with the calcium antagonist, felodipine.

1 Twelve non-diabetic hypertensive male patients insufficiently controlled by a diuretic were included in a double-blind, randomised study. In addition placebo or felodipine was given for 4 weeks followed by a 2 week wash-out period, after which the alternative treatment was given for another 4 weeks. At the end of each treatment period an oral glucose tolerance test (OGTT) was performed and blood pressure, plasma noradrenaline and felodipine levels were measured. 2 There was no change in either glucose, insulin or glucagon levels during the OGTT after felodipine compared with placebo. Blood pressure was significantly reduced during the dosage interval of felodipine (12 h). Plasma noradrenaline increased significantly after felodipine. Side effects were few. 3 In a separate open study 58 hypertensive patients were treated with felodipine in addition to a diuretic and a beta-adrenoceptor blocker for up to 1 year. There were no significant changes in fasting blood glucose levels during the study.

Blood Glucose↗
PubMed1987

A microdialysis method allowing characterization of intercellular water space in humans.

To evaluate the usefulness of the tissue-microdialysis technique in humans, the glucose concentration in the intercellular water space was measured in the abdominal subcutaneous region in healthy subjects. A 30 X 0.3 mm dialysis fiber with a 3,000 MW cutoff was used. The dialysis catheter was calibrated in vivo by perfusing it with isotonic saline and four to five different glucose concentrations (0-5 mM). The perfusate was collected in 6-min fractions. Regression analysis of the results of the calibration yielded the perfusate glucose concentration, which was in equilibrium with the surrounding tissue. Validation experiments showed that this value could be precisely measured and represented the intercellular glucose concentration. The recovery of glucose in the dialysate (dialysate glucose concentration/medium) during the calibrations in vivo was only approximately one-half of that in vitro (recovery factors 0.28 vs. 0.44, respectively). Under steady-state conditions, the intercellular glucose concentration was similar to the glucose levels in the cubital vein. It is concluded that this microdialysis technique is a useful tool allowing measurements of metabolically active substances in the intercellular water space in vivo provided that the calibrations are properly performed.

Adult↗
PubMed1987

Early posthypoglycemic insulin resistance in man is mainly an effect of beta-adrenergic stimulation.

The insulin effect following hypoglycemia was studied with the euglycemic clamp technique in seven healthy subjects. Following an initial euglycemic clamp hypoglycemia was induced and after glucose recovery a second clamp was performed. Glucose production (Ra) and utilization (Rd) were studied with [3-3H]glucose. Each subject was studied four times; during infusion of placebo, propranolol, somatostatin, and a control study where hypoglycemia was prevented. Hypoglycemia induced an insulin resistance with a lower steady state glucose infusion rate following the hypoglycemia during placebo as compared to the control study (2.5 +/- 0.5 and 4.8 +/- 1.0 mg/kg min, respectively, P less than 0.05). The insulin resistance was due to an attenuated insulin effect on both inhibition of Ra (impaired by 37%) and stimulation of Rd (impaired by 61%). The insulin-antagonistic effect was completely prevented by propranolol but only partly by somatostatin. Thus, early posthypoglycemic insulin resistance (2.5-3.5 h after hypoglycemia) is a sustained effect mainly due to beta-adrenergic stimulation.

Adult↗
PubMed1987

Dietary fibre, diabetes and obesity.

An increased intake of dietary fibre appears to be useful for the treatment of both obesity and diabetes mellitus. Fibre-rich food is usually satisfying without being calorically dense. Supplementing a normal diet with gel-forming fibres, such as guar gum, leads to an increased satiation probably due to a slower gastric emptying. Recent long-term studies have confirmed the usefulness of viscous fibres as an adjunct to regular dietary treatment of obesity. Apart from a beneficial effect during caloric restriction, dietary fibre may improve some of the metabolic aberrations seen in obesity. Gel-forming fibres are particularly effective in reducing elevated LDL-cholesterol without changing the HDL-fraction. Impaired glucose tolerance or manifest diabetes is also improved. These effects are probably in part associated with the gelling property of the fibre which leads to an increased viscosity of the unstirred layer thereby delaying the absorption process. Other sources of dietary fibre with a high content of viscous gums, such as oats, have been shown to reduce LDL-cholesterol. Increased intake of viscous fibre leads to a gradual reduction in fasting glucose levels in diabetics. The reason for this is unclear but it cannot readily be explained by a delayed absorption process. Since insulin levels are also reduced these findings suggest that insulin resistance is alleviated. Recent studies with the euglycemic clamp technique support this possibility. Glucose uptake by isolated fat cells and both insulin sensitivity and responsiveness are also increased.

Body Weight↗
PubMed1987

Regional adipose tissue metabolism in men and postmenopausal women.

The metabolism of subcutaneous abdominal and femoral fat cells was studied in postmenopausal women and matched men of similar age and weight index. Lipoprotein lipase (LPL) activity was similar in both regions in the postmenopausal women. However, a group of women who underwent treatment with estrogen and progestins had considerably higher LPL activity in the femoral cells. Testosterone treatment for 7 days did not change LPL in either region in middle-aged men. Femoral adipocytes from both men and postmenopausal women were markedly unresponsive to catecholamine in comparison with abdominal cells. No clear effect of the sex hormones was seen on lipolysis in the women. Treating men with testosterone increased basal lipolysis in the abdominal cells. Abdominal fat cells were more responsive to the antilipolytic effect of insulin. Both responsiveness and sensitivity to insulin were somewhat greater in the abdominal fat cells from men (ED50 approximately 0.02 nm) than from women (ED50 approximately 0.17 nm). Insulin binding, however, was similar in fat cells from the abdominal and the femoral regions when the results were expressed per unit surface area. Thus, regional differences in fat cell metabolism are seen in both postmenopausal women and elderly men. LPL activity in the femoral region seems to be under the control of female sex hormones while lipolysis appears to be less influenced by sex hormones.

Adipose Tissue↗
PubMed1987

Metformin enhances insulin binding to "in vitro" down regulated human fat cells.

Insulin binding to human adipose tissue from surgical patients was determined after three different preincubation conditions: a) 24 hrs in the presence or absence of 80 ng/ml insulin; b) 24 hrs in the presence of 80 ng/ml insulin or insulin plus 4 micrograms/ml metformin; c) 48 hrs pre-incubation as in b). We found that insulin down regulated its own receptor after 24 hours pre-incubation; when metformin was present in the pre-incubation medium together with insulin, insulin binding to adipose tissue was significantly higher than in tissue exposed to insulin alone after 48 hrs pre-incubation; a similar effect of metformin was already seen after 24 hrs, but was not statistically significant. We suggest that metformin can correct down regulation of the insulin receptor. This finding could explain discrepant results among studies dealing with the influence of metformin on insulin binding. Moreover, these results could be useful in understanding the mechanism of action of metformin in insulin-resistant states, e.g. type II diabetes.

Adipose Tissue↗
PubMed1987

Recognizing hyperthyroidism in the elderly.

Hyperthyroidism in the elderly frequently presents with atypical symptoms such as apathy, anorexia, diarrhea, atrial fibrillation, and (or) cardiac decompensation. The diagnosis may therefore be delayed or missed, as illustrated by three cases. Laboratory thyroid evaluation is justified by a wide variety of indications in elderly persons who seek medical advice or care.

Aged↗
PubMed1986

The antilipolytic effect of insulin in human adipocytes requires activation of the phosphodiesterase.

Human fat cells were incubated with two different cAMP analogues, 8-bromocAMP and 6N-monobutyrylcAMP. The former analogue is an excellent substrate for the phosphodiesterase while the latter is resistant to hydrolysis. In the presence of adenosine deaminase, isoproterenol (10(-6)M) stimulated lipolysis 8-10 fold which was similar to the effect exerted by the cAMP analogues. Basal lipolysis and lipolysis activated by 6N-monobutyrylcAMP was not inhibited by insulin even at high concentrations, whereas the effect of 8-bromocAMP was virtually completely inhibited. This effect of insulin was completely prevented by the addition of IBMX. Thus, activation of phosphodiesterase by insulin is necessary to elicit the antilipolytic effect in human adipocytes.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Specific binding of human growth hormone but not insulin-like growth factors by human adipocytes.

Binding of human GH (hGH) and insulin-like growth factors I and II (IGFI and II) to isolated human adipocytes from adult subjects was studied. Binding equilibrium for hGH at 24 degrees C was reached at 120 min and half-maximal specific binding at 6-8 ng/ml. Apparent Ka was 2.1 X 10(9) M-1 and Bmax 7.3 X 10(-11) M/10(6) cells. The human fat cell growth hormone receptor recognized neither bovine, ovine or rat GH nor human prolactin or placental lactogen. No specific receptors for human IGFII could be demonstrated. Thus, human adipocytes do not possess IGF receptors but have specific GH receptors which recognize hGH but not GH from lower species.

Adipose Tissue↗
PubMed1986

Structure of Rhodopseudomonas sphaeroides R-26 reaction center.

The molecular replacement method has been successfully used to provide a structure for the photosynthetic reaction center of Rhodopseudomonas sphaeroides at 3.7 A resolution. Atomic coordinates derived from the R. viridis reaction center were used in the search structure. The crystallographic R-factor is 0.39 for reflections between 8 and 3.7 A. Validity of the resulting model is further suggested by the visualization of amino acid side chains not included in the R. viridis search structure, and by the arrangements of the reaction centers in the unit cell. In the initial calculations quinones or pigments were not included; nevertheless, in the resulting electron density map, electron density for both quinones QA and QB appears along with the bacteriochlorophylls and bacteriopheophytins. Kinetic analysis of the charge recombination shows that the secondary quinone is fully functional in the R. sphaeroides crystal.

Bacterial Proteins↗
PubMed1986

Heliobacterium chlorum: cell organization and structure.

The basic cellular organization of Heliobacterium chlorum is described using the freeze-etching technique. Internal cell membranes have not been observed in most cells, leading to the conclusion that the photosynthetic apparatus of these organisms must be localized in the cell membrane of the bacterium. The two fracture faces of the cell membrane are markedly different. The cytoplasmic (PF) face is covered with densely packed particles averaging 8 nm in diameter, while the exoplasmic (EF) face contains far fewer particles, averaging approximately 10 nm in diameter. Although a few differentiated regions were noted within these fracture faces, the overall appearance of the cell membrane was remarkably uniform. The Heliobacterium chlorum cell wall is a strikingly regular structure, composed of repeating subunits arranged in a rectangular pattern at a spacing of 11 nm in either direction. We have isolated cell wall fragments by brief sonication in distilled water, and visualized the cell wall structure by negative staining as well as deep-etching.

Bacteria↗
PubMed1986

Studies on the insulin-antagonistic effect of catecholamines in normal man. Evidence for the importance of beta 2-receptors.

The insulin-antagonistic effect of adrenaline was studied in seven healthy subjects with the euglycaemic clamp technique using two insulin infusion rates (40 and 1200 mU X (m2)-1 min-1). The adrenergic receptor mediating the adrenaline effect was characterized by concomitant infusion of propranolol (beta 1 + beta 2-antagonist) or metoprolol (beta 1-antagonist). Each subject was studied four times (placebo, adrenaline, adrenaline + propranolol, adrenaline + metoprolol). Glucose turnover was measured with D(3-3H)-glucose. Similar plasma insulin levels were reached in all studies with the two insulin infusion rates (mean; placebo 51 +/- 3 and 7421 +/- 337 mU/l respectively). Glucose production was completely inhibited by the low insulin level during placebo infusion. Adrenaline antagonized this effect so that a significant glucose production was seen at the low but not at the high insulin level. Propranolol, but not metoprolol, reversed this insulin-antagonistic effect of adrenaline. Glucose utilization increased from 2.53 +/- 0.17 to 7.28 +/- 0.88 mg X kg-1 X min-1 during placebo when the insulin levels were increased from 4 +/- 0.3 to 51 +/- 3 mU/l. Increasing the insulin levels 150-fold to approximately 7500 mU/l only doubled the glucose utilization (14.68 +/- 1.14 mg X kg-1 X min-1). Adrenaline induced a pronounced inhibition of glucose utilization at both insulin levels (78% and 37% inhibition respectively). Propranolol, but not metoprolol, prevented this effect of adrenaline. Thus, physiological adrenaline levels exert a pronounced insulin-antagonistic effect which is mediated by beta 2-receptor stimulation. The inhibitory effect on glucose uptake is maintained even at high insulin levels when hepatic glucose production is completely abolished.

Adult↗
PubMed1986

Clinical aspects of beta-blockade.

beta-Blocking drugs have no or only a partial beta-agonistic activity (ISA). Since they all bind to beta receptors, they act as competitive inhibitors of the endogenous catecholamines. In addition to this common effect, the beta-blocking drugs also have other properties that may be clinically important, such as extent of beta 1 selectivity, ISA, and lipophilicity. The importance of these properties in the clinical setting is reviewed.

Adrenergic beta-Antagonists↗
PubMed1986

Aging enhances the insulin resistance in obesity through both receptor and postreceptor alterations.

The association between aging and insulin resistance is well recognized. To clarify possible mechanisms, both the binding and the action of insulin were studied in abdominal sc fat cells from two groups of obese nondiabetic women matched for relative weight and fasting insulin levels. The age ranges of the two groups were 16-37 (mean, 28) and 47-77 (mean, 61) yr, respectively. Insulin binding was significantly decreased in the elderly (approximately 40%; P less than 0.05), which Scatchard analysis showed to be due to a decreased number of binding sites. In accordance with the binding data, the dose-response curve for insulin's stimulatory effect on glucose incorporation into triglycerides was shifted to the right. Glucose incorporation in the absence of insulin was similar in both groups, whereas the increment induced by a maximally stimulating concentration of insulin was reduced in the elderly (approximately 50%; P less than 0.02), suggesting the presence of a postreceptor defect. A negative correlation was found between insulin response and age. Thus, in the presence of obesity, aging is associated with resistance to the stimulatory effect of insulin on glucose metabolism in adipocytes. The insulin resistance is due to both receptor and postreceptor perturbations.

Adipose Tissue↗
PubMed1985

Characterization of bacterial photosynthetic reaction center crystals from Rhodopseudomonas sphaeroides R-26 by X-ray diffraction.

An orthorhombic crystal form (P2(1)2(1)2(1)) of the reaction center from the photosynthetic bacterium Rhodopseudomonas sphaeroides R-26 has been characterized. The crystals were grown from polyethylene glycol; the unit cell dimensions are a = 142.2 A, b = 139.6 A, and c = 78.7 A; and they contain one reaction center in each crystallographic asymmetric unit. The crystals diffract to at least 3.0 A resolution, and are suitable for detailed structural studies.

Bacterial Proteins↗
PubMed1985

Bacitracin enhances intracellular accumulation of insulin in rat adipocytes.

Bacitracin (1 mg/ml) markedly increased (approx. 75%) the cell-associated specifically bound 125I-labelled insulin without altering the affinity of the binding sites. Bacitracin also exerted a modest inhibitory effect on the degradation of insulin in the incubation medium determined as radioactivity not precipitated by trichloroacetic acid (from 9.6 to 4.8%). The effect on insulin binding was about 5-times as sensitive as the effect on degradation. The increased binding was due to intracellular accumulation of radioactivity which could not be removed by treating the cells with trypsin. This increase was not seen when the internalization process was reduced by ATP-depletion or low temperature. Since the trypsin-sensitive fraction of cell-associated radioactivity was apparently not altered, it is suggested that bacitracin, in addition to its well-known inhibition of extracellular degradation, also inhibits the intracellular degradation of insulin.

3-O-Methylglucose↗
PubMed1985

The effects of physical training on insulin secretion and effectiveness and on glucose metabolism in obesity and type 2 (non-insulin-dependent) diabetes mellitus.

Obese subjects with normal glucose tolerance (n = 55), and, in another study, a group of patients with Type 2 (non-insulin-dependent) diabetes (n = 33), and controls (n = 13) matched for body weight and age but with normal glucose tolerance, participated in an individualized physical training program for 3 months. Under controlled dietary conditions, metabolic studies were performed before and in steady state after the last exercise session after training in the subjects showing signs of physical training in VO2 max and heart rate measurements. No changes occurred in body weight, body cell mass, body fat or adipose tissue cellularity. Oral glucose tolerance was improved in the patients with diabetes mellitus only. In both diabetic and control subjects initially elevated C-peptide concentrations decreased, while low C-peptide values increased and which was particularly pronounced in diabetic subjects with subnormal values. Peripheral insulin values did not change. Glucose disposal rate measured with the glucose clamp technique was similar in diabetic patients and control subjects. An improvement was seen at both submaximal and maximal insulin levels in both groups, correlating with improvement in glucose tolerance in the diabetic subjects. No changes were found in adipocytes in insulin binding or the antilipolytic effect of insulin at submaximal insulin levels, but there was a normalization of a decreased glucose incorporation into triglycerides. These results indicate that both insulin secretion and effectiveness are altered by physical training in different ways in different clinical entities. They suggest that in insulin resistant conditions with high insulin secretion (as indicated by high C-peptide concentrations) the increased peripheral insulin sensitivity is followed by a decreased insulin secretion. This is not associated with an improvement of glucose tolerance. In Type 2 diabetes with low insulin secretion, an increased insulin secretion results from physical training, perhaps due to accompanying sensitization of the autonomic nervous system. Peripheral insulin concentrations are not altered, suggesting that the extra insulin produced is captured by the liver. This mechanism, as well as the improved peripheral insulin responsiveness seen in the whole body and also seen at the cellular level, probably both contribute to an improvement in glucose tolerance.

Adipose Tissue↗