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Biomedical subjects

U Smith

Publications and source records attributed to U Smith.

At least 163 records · Page 9Linked to original sources
PubMed1985

Reduced insulin binding to human fat cells following beta-adrenergic stimulation--experimental evidence and studies in patients with a phaeochromocytoma.

The effect of beta-adrenergic stimulation on insulin binding was studied in human fat cells in vitro. Isoproterenol rapidly (approximately 5 min) reduced insulin binding through a beta-adrenergic and dose-dependent mechanism. The reduced binding was enhanced by the addition of adenosine deaminase and was also elicited by the addition of dibutyryl cAMP. This effect was due to a decreased number of binding sites. The reduction was rapidly reversed by propranolol (t1/2 approximately 10 min) and other beta-adrenoreceptor blocking agents. Insulin binding was also measured in fat cells from 6 patients with a phaeochromocytoma. A significant negative correlation between tracer binding and the log value of total urinary catecholamine excretion was found (r = -0.821, p less than 0.05). Mean tracer insulin binding was reduced about 30% as compared to cells from 16 carefully matched control subjects. Decreased insulin binding was again mainly attributable to a decreased number of binding sites. Thus, beta-adrenergic stimulation, both in vitro and in vivo, leads to a decreased number of binding sites for insulin in human fat cells.

Adipose Tissue↗
PubMed1985

Changes in growth hormone binding and metabolic effects of growth hormone in rat adipocytes following hypophysectomy.

Growth hormone (GH) binding and the effect of GH and insulin on glucose metabolism in rat adipocytes were studied at various time periods following hypophysectomy. Male rats were hypophysectomized at 33-34 days of age. After 6 h, 20 h or 3, 7 and 14 days adipocytes were prepared from epididymal fat pads by mild collagenase digestion (0.5 mg X ml-1, 60 min, 37 degrees C). Glucose metabolism was studied by determining the production of CO2 from [14C]glucose and the incorporation of [14C]glucose into lipids. GH binding was measured in cell aliquots using [125I]hGH. No difference in GH binding to adipocytes was observed between control rats and rats hypophysectomized or sham-operated 6 h earlier. GH binding was significantly decreased 20 h after hypophysectomy and declined further with time after hypophysectomy. Adipose tissue from normal rats is usually refractory to the insulin-like effect of GH. Adipocytes isolated from normal rats were, however, usually responsive to GH immediately after cell isolation, suggesting that refractoriness to the insulin-like effect of GH was lost during the time required for the preparation of adipocytes. The magnitude of the response to GH in adipocytes progressively declined with time after hypophysectomy. The decreased responsiveness to GH with time after hypophysectomy parallelled the decrease in GH binding. The results suggest that the pituitary, directly or indirectly, is necessary for the maintenance of GH binding sites in adipose tissue and that these binding sites are related to the insulin-like effect of GH.

Adipose Tissue↗
PubMed1985

Fat cell metabolism in different regions in women. Effect of menstrual cycle, pregnancy, and lactation.

Adipose tissue lipolysis and lipoprotein lipase (LPL) activity were studied in biopsies from the femoral and abdominal depots in healthy women during early or late menstrual cycle, pregnancy, and the lactation period. When the differences in cell size were taken into account, basal lipolysis was similar in both regions in nonpregnant women. During lactation, however, lipolysis was significantly higher in the femoral region. The lipolytic effect of noradrenaline (10(-6) M) was significantly less in the femoral region in the nonpregnant women and during early pregnancy. However, the lipolytic response was the same in both regions in lactating women. LPL activity was higher in the femoral than in the abdominal region except during lactation when a marked decrease in the LPL activity was seen in the femoral region. The LPL activity in the abdominal region remained unchanged in all patient groups. The results imply that in both nonpregnant and pregnant women lipid assimilation is favored in the femoral depot. During lactation, however, the metabolic pattern changes; the LPL activity decreases and lipid mobilization increases in this depot. These changes are much less pronounced in the abdominal region. Thus, fat cells from different regions show a differential response during pregnancy and lactation. These results suggest that the adipose tissue in different regions may have specialized functions.

Abdomen↗
PubMed1985

Glucagon release and glucose counter-regulation during hypoglycaemia. Modifying effect of the previous glucose level.

The importance of a short-term elevation of the ambient glucose level for the release of counter-regulatory hormones and the glucose recovery rate during a subsequent hypoglycaemia was studied in healthy subjects. Hypoglycaemia was induced with insulin infusion after a previous 80 min of euglycaemic (E: 5 mmol/l) or hyperglycaemic (H: 15 mmol/l) glucose clamp. By infusing insulin during the euglycaemic clamp similar levels were reached during both glucose clamps. The same level of hypoglycaemia was reached in both studies (E: 1.5 +/- 0.1, H: 1.5 +/- 0.2 mmol/l) and the insulin levels were also similar both at glucose nadir and during the recovery period. In spite of this, both the mean glucagon levels at nadir at the mean individual maximal increase were significantly lower after the hyperglycaemic clamp (E: 101 +/- 25, H: 54 +/- 7 pg/ml, P less than 0.05). The glucose recovery rate was also significantly impaired following the hyperglycaemic clamp. The results show that a short-term elevation of the ambient glucose level impairs the glucagon release during a subsequent hypoglycaemia. This finding may be of importance for the development of the blunted glucagon release in response to low glucose levels in diabetics.

Adult↗
PubMed1985

Mechanism of insulin's stimulatory action on glucose transport in the isolated rat adipose cell.

The mechanism by which insulin stimulates glucose transport in the rat adipose cell has been shown to be a rapid, reversible, and energy-dependent process. Stimulation is achieved by the translocation of glucose transporters from an intracellular pool to the plasma membrane where their insertion is ultimately responsible for the increase in transport activity. The reversal of this process also occurs rapidly at 37 degrees C, with the transporters reappearing in the intracellular pool. The overall cycle thus appears as a reversible endocytic-exocytic process with the endocytic and exocytic steps showing markedly different kinetic properties. Studies of the effects of incubation temperature and TRIS confirm the existence of an intermediate state in which transporters are associated with the plasma membrane but incapable of transporting extracellular glucose. This suggests that insulin may act at the level of the plasma membrane at the step that results in the exposure of functional glucose transporters. The existence of a cAMP-mediated process capable of overriding the actions of insulin raises the possibility of a second level of control of glucose transport activity the significance of which remains to be assessed. Finally, a third control mechanism exists for regulating the absolute number of glucose transporters per cell that appears to be specifically affected in certain pathophysiological conditions in the rat.

Adipose Tissue↗
PubMed1985

Regional differences in adipocyte metabolism and possible consequences in vivo.

Recent studies have shown that adipose tissue metabolism varies in different regions. Thus, hormonal responsiveness and sensitivity to both lipolytic and anti-lipolytic agent is increased in abdominal as compared to femoral cells. Abdominal obesity is also associated with greater aberrations in metabolism than peripheral obesity. The increased lipolytic response in abdominal fat cells may lead to higher FFA concentrations, which may attenuate both glucose uptake and insulin clearance by the liver.

Abdomen↗
PubMed1985

Insulin binding in differentiating rat preadipocytes in culture.

Binding, degradation, and antilipolytic effect of insulin were studied during the differentiation of preadipocytes into unilocular adipocytes. The precursor cells were isolated from the stromal-vascular fraction of adult rat epididymal fat pads and were cultured according to methods previously described. Under appropriate conditions the cells attained full morphological maturation after 6 days. A gradual increase in insulin binding was found concomitant with the morphological development of the preadipocytes into adipocytes. This increase was due to an enhanced number of binding sites whether expressed per cell or per unit cell surface area. The presence of a high insulin concentration (1.67 micrograms/ml or 278 nM) in the culture medium did not prevent this effect. The receptor density, expressed per unit surface area, was higher in the newly developed univacuolar cells than in mature fat cells from the same rat. The increased receptor density was also reflected by a leftward shift in the dose-response curve for the antilipolytic effect of insulin. In parallel with the increased binding, insulin degradation also increased. The lipolytic response to catecholamine also showed a gradual increase with development. When expressed per unit surface area, newly formed cells exhibited a considerably greater response (approximately 3.4 times) than mature cells from the same animals. The maximal antilipolytic effect of insulin in new cells was of the same order as in old cells when the data were expressed per unit cell surface area. Thus, the data show that developing adipocyte precursors gain membrane properties similar to those of mature fat cells. This cell system may serve as a useful model for studying receptor formation and factors that regulate hormone responsiveness.

Adipose Tissue↗
PubMed1984

Counter-regulation of insulin-stimulated glucose transport by catecholamines in the isolated rat adipose cell.

The interaction between catecholamines and insulin in regulating glucose transport in isolated rat adipose cells has been evaluated. In the absence of insulin, 1 microM isoproterenol stimulates 3-O-methylglucose transport approximately 2-fold. However, isoproterenol in combination with adenosine deaminase inhibits glucose transport activity approximately 60%. N6-Phenylisopropyladenosine, a nonmetabolizable adenosine analogue, substantially reverses this inhibitory effect and actually stimulates glucose transport activity approximately 2-fold in the absence of isoproterenol. Dibutyryl cAMP inhibits glucose transport activity approximately 75% regardless of adenosine deaminase. While none of these agents significantly influences the basal concentration of plasma membrane glucose transporters, as assessed by specific D-glucose-inhibitable cytochalasin B binding, isoproterenol or dibutyryl cAMP in combination with adenosine deaminase reduces that in the low density microsomes 19 and 58%, respectively. In the presence of insulin, both isoproterenol and adenosine deaminase alone inhibit glucose transport activity approximately 25%. However, only the latter is accompanied by a corresponding decrease in the insulin-stimulated concentration of plasma membrane glucose transporters. Together, isoproterenol and adenosine deaminase inhibit insulin-stimulated glucose transport activity approximately 75%, even in the presence of 5 mM glucose to maintain cellular ATP levels. A similar inhibition is observed with dibutyryl cAMP. However, these agents decrease the insulin-stimulated concentration of plasma membrane glucose transporters only approximately 45%. Nevertheless, all of these inhibitory effects occur through decreases in the transport Vmax. In addition, N6-phenylisopropyladenosine partially reverses the inhibitory effects induced by the presence of adenosine deaminase. These results suggest that catecholamines counter-regulate basal and insulin-stimulated glucose transport in rat adipose cells through a cAMP-mediated mechanism, but only in part by modulating the translocation of glucose transporters.

3-O-Methylglucose↗
PubMed1984

Improved but not normalized glucose counter-regulation during glucagon infusion in Type 1 (insulin-dependent) diabetes.

Glucose counter-regulation during insulin-induced hypoglycaemia was studied in Type 1 diabetic patients without evidence of autonomic neuropathy and compared with that of a non-diabetic control group. The glucose recovery rate following hypoglycaemia was delayed in the diabetic compared with the control subjects and this was most pronounced for the initial, rapid phase of glucose increase (glucose increase in 15 min, control: 1.1 +/- 0.1 versus 0.4 +/- 0.1 mmol/l; p less than 0.01). The release of glucagon during hypoglycaemia was blunted in the diabetic patients (maximal plasma levels, control: 148 +/- 25 versus 70 +/- 10 pg/ml; p less than 0.01). The adrenaline levels were also lower compared with the control subjects (maximal plasma levels, control: 7.23 +/- 1.21 versus 3.27 +/- 0.87 nmol/l; p less than 0.05). To evaluate the importance of the blunted glucagon response for the delayed glucose compensation, glucagon was infused during the hypoglycaemia. Overall glucose recovery rate was improved but did not return to normal. Consequently impaired glucagon release in the diabetic patients cannot alone explain impaired glucoregulation; the lower adrenaline levels and/or an effect of the previous glucose levels per se on hepatic glucose production are probably also of importance.

Adult↗
PubMed1984

Cells in human adipose tissue developing into adipocytes.

Sedimentable cells from human adipose tissue of different origins were cultured under conditions when cell multiplication was prevented but lipid filling optimized (suspension culture). In this way an estimation was obtained of the number of in vivo determined adipose precursor cells (preadipocytes) which were not filled with lipid. Under these conditions no cells from adult, non-obese subjects developed to adipocytes. Cells developing to adipocytes constituted less than 0.02% and 1% of adipocytes in tissues from obese adults and from children, respectively. It was concluded that in vivo determined adipocyte precursor cells (preadipocytes, lipid-free fat cells) are not present in a significant number in human adipose tissue either from adults or from children as tested with the method employed, allowing detection of a large number of such cells in adipose tissue from small rats.

Adipose Tissue↗
PubMed1984

Diabetes mellitus in phaeochromocytoma. Fasting blood glucose levels before and after surgery in 60 patients with phaeochromocytoma.

Sixty patients undergoing operation for phaeochromocytoma were investigated in the pre- and postoperative states with respect to fasting blood glucose levels. When 6 previously known or suspected diabetics were excluded, preoperative diabetes (fasting blood glucose levels greater than or equal to 7.0 mmol/l) were found in 3 of 13 (23%) with sustained hypertension, in 6 of 12 (50%) with sustained hypertension associated with paroxysms and in 4 of 24 (17%) with paroxysmal hypertension. None of the 5 patients with atypical clinical symptoms had glucose levels greater than or equal to 7.0 mmol/l. In the groups of patients with particularly high urinary excretion of catecholamines and vanilmandelic acid higher blood glucose levels were also found. The postoperative blood glucose levels in the follow-up study were normal and less than 5.8 mmol/l in all cases except in 3 of the 4 still living patients with a previously known diabetes and in 1 patient with a malignant tumour. Thus, manifest diabetes, defined as fasting glucose levels greater than or equal to 7.0 mmol/l, is frequently present in patients with phaeochromocytoma (24% in the present study) and the diabetes is reversed by removal of the tumour.

Adrenal Gland Neoplasms↗
PubMed1984

Effects of physical training on insulin, connecting peptide (C-peptide), gastric inhibitory polypeptide (GIP) and pancreatic polypeptide (PP) levels in obese subjects.

Ten severely obese women were subjected to physical training for three months on ad libitum diet. Under metabolic ward conditions oral glucose tolerance test was performed before and after the training period with the same energy intake quantitatively and qualitatively, and glucose, insulin, connecting (C)-peptide, gastric inhibitory polypeptide (GIP) and pancreatic polypeptide (PP) were determined. In confirmation of previous work, physical training caused no decrease in body fat in these severely obese subjects, and no change in body cell mass or glucose tolerance, while insulin and blood pressure decreased. The control of dietary conditions demonstrated that the latter phenomena were not due to quantitative or qualitative changes in the diet. C-peptide concentrations decreased also, indicating effects of physical training in obesity on insulin production. GIP is believed to be a gastrointestinal factor facilitating insulin secretion (Incretin). Previous work has indicated that gastrointestinal factor(s) are involved in the insulin lowering effect seen after physical training. It is possible that GIP is contributing to this phenomenon.

Adipose Tissue↗
PubMed1984

Influence of metformin on metabolic effect of insulin in human adipose tissue in vitro.

To study the mechanism(s) of action of metformin, fragments of human subcutaneous adipose tissue were incubated with therapeutic blood concentrations of metformin. In the absence of insulin no effect of metformin was seen on either lipolysis or glucose metabolism. When insulin was present, however, metformin stimulated glucose conversion into both triglycerides and CO2. In marked contrast, no effect of metformin was observed on the antilipolytic effect of insulin. In agreement with this selective effect no change in insulin binding was found. In conclusion, metformin seems to exert its effect on glucose metabolism by potentiating the action of insulin at a post-receptor level, possibly on the rate of glucose transport.

Adipose Tissue↗
PubMed1983

Reversal of insulin resistance in type I diabetes after treatment with continuous subcutaneous insulin infusion.

Insulin responsiveness was studied with the euglycaemic glucose clamp technique in seven patients with type I diabetes and in six control subjects matched for age and weight. The glucose disposal rate was significantly reduced in the diabetic subjects when they were receiving conventional insulin treatment compared with the control group, showing insulin resistance in the diabetics. The diabetic patients were again studied after eight days of intensified metabolic control achieved with continuous subcutaneous insulin infusion. During the infusion a more physiological insulin regimen was used compared with their regular treatment, less of the total insulin dose being given as continuous infusion and more as bolus doses before meals. The insulin resistance in the diabetics was largely reversed after this improved metabolic control. Dose response studies showed an increased glucose disposal rate at all plasma insulin concentrations, including the maximum insulin concentration, indicating a predominant effect of the continuous infusion regimen at the postreceptor level. The improved insulin effect seen with continuous subcutaneous insulin infusion could be due to the improved metabolic control achieved as well as the more physiological regimen.

Adult↗
PubMed1983

beta-Adrenergic dependent downregulation of insulin binding in rat adipocytes.

In order to study factors regulating insulin binding to rat adipocytes short- and long-term incubations were performed in the presence or absence of noradrenaline (NA) at a concentration of 3 microM. Culture with NA for 24 hours resulted in a significant decrease (30%) of insulin binding due to a reduced number of binding sites. This reduction was dose-dependent and completely prevented by the addition of timolol, a beta-adrenergic blocking agent, but not by the alpha-blocking agent phentolamine. Addition of 1.0 mM db cAMP to the culture medium resulted in a similar reduction in insulin binding. Also short-term incubations with NA resulted in a downregulation of insulin binding; reproducible reductions seen already after 20 min and about 30% reduction achieved after 2 hours' preincubation. Thus, beta-adrenergic stimulation and subsequent cAMP elevation results in a rapid reduction in the number of insulin binding sites.

Adipose Tissue↗
PubMed1983

Influence of ambient glucose and insulin concentrations on adipocyte insulin binding.

To elucidate factors of importance for insulin binding, fat cells from humans and rats were incubated under various experimental conditions for different periods of time. Human adipocytes incubated for 24 hours in the absence of insulin showed no significant difference in insulin binding compared with cells from freshly excised tissue. After 48 hours, however, an increased rate of binding (average 54%; P less than 0.05) was obtained. The addition of insulin (2000 microU/ml) to the culture medium resulted in a decrease in insulin binding (average 33%; P less than 0.05) compared with cells maintained in the absence of insulin. There was no apparent difference in receptor affinity, indicating that the altered binding was due to a change in receptor number. In the absence of insulin, elevating the glucose concentration of the medium from 0.8 mM to 22.4 mM did not significantly influence insulin binding. Rat adipocytes showed similar but more rapid changes. Thus, incubation for 24 hours without insulin caused an increase in insulin binding (average 37%; P less than 0.05). This up-regulation was seen even in a high glucose concentration (28 mM) but was completely prevented by the presence of insulin in the medium. Furthermore, when rat adipocytes were incubated with insulin in the presence of a high glucose concentration (28 mM) there was a significant further decrease in insulin binding compared with that of parallel incubations performed in 5.6 mM glucose. Thus, even in the absence of TRIS buffer, insulin-dependent regulation of the number of binding sites is shown for both human and rat adipocyte tissue in vitro. Although this perturbation could be directly due to hormone-receptor interaction at the membrane level, the finding of rat adipocytes that the ambient glucose concentration can modulate this effect suggests the importance of post-receptor events.

Adipose Tissue↗
PubMed1983

Adrenergic control of lipid metabolism.

Adrenergic receptors are ubiquitous and mediate several important effects involving lipid metabolism. Thus, beta-adrenergic stimulation increases lipolysis and inhibits the activity of the lipoprotein lipase. In contrast, alpha-adrenergic stimulation inhibits fat cell lipid mobilisation. Unexpectedly, beta-adrenergic blockade increases plasma triglyceride levels and tends to lower the high density lipoprotein (HDL-cholesterol). These effects seem to be prevented or attenuated by concomitant alpha-blockade. Possible mechanisms for the adrenergic effect on lipid metabolism are reviewed.

Adrenergic beta-Agonists↗