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Biomedical subjects

O Pedersen

Publications and source records attributed to O Pedersen.

At least 253 records · Page 14Linked to original sources
PubMed1983

Increased insulin binding to adipocytes and monocytes and increased insulin sensitivity of glucose transport and metabolism in adipocytes from non-insulin-dependent diabetics after a low-fat/high-starch/high-fiber diet.

Nine non-insulin-dependent diabetics were studied before and after 3 weeks on an isoenergetic high-fiber/high-starch/low-fat diet (alternative diet), and nine non-insulin-dependent diabetics were studied on their usual diet. In the group that ate the alternative diet, the intake of fiber and starch increased 120% and 53%, whereas fat intake decreased 31%. Diabetes control improved as demonstrated by decreased fasting plasma glucose (P less than 0.05) and 24-hour urinary glucose excretion (P less than 0.05). The in vivo insulin action increased (KIVITT increased, P less than 0.05) with no change in fasting serum insulin levels. In fat cells obtained from patients in the alternative-diet group, insulin receptor binding increased (P less than 0.05) after the change of diet. Insulin binding to purified monocytes (more than 95% monocytes) also increased (P less than 0.05), whereas no change was found in insulin binding to erythrocytes. When lipogenesis was studied at a tracer glucose concentration at which glucose transport seems to be rate limiting, insulin sensitivity increased (P less than 0.02). This is the predicted consequence of increased receptor binding. Moreover, when CO2 production and lipogenesis were studied at a higher glucose concentration, where steps beyond transport seem to be rate limiting for glucose metabolism, increased insulin sensitivity was also observed. In contrast, no change was found in maximal insulin responsiveness. Fat and blood cells from the patients who continued on their usual diet showed no changes of the mentioned quantities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1983

The effect of glibenclamide on insulin receptors in normal man: comparative studies of insulin binding to monocytes and erythrocytes.

In vivo studies in noninsulin-dependent diabetic patients have indicated that sulphonylurea drugs have an extra-pancreatic effect. To further elucidate the mechanisms of this action, we studied the effect of glibenclamide on in vivo and in vitro cellular insulin receptor binding in normal subjects. Oral administration of glibenclamide in dose of 2.5 mg/day increased insulin binding to monocytes by 70% (P less than 0.001), in spite of increased postprandial serum insulin levels. This change in insulin receptor binding occurred in the absence of changes in diet or body weight. In contrast, glibenclamide had no stimulatory effect on in vivo insulin binding to erythrocytes. The in vitro studies with monocytes revealed a dose-related insulin receptor stimulatory effect of glibenclamide (P less than 0.05), with a maximal effect of 20% above basal level. These data indicate that glibenclamide increases the insulin-binding ability of monocytes but not of erythrocytes. As the monocyte is judged a better model for studying insulin receptors on target cells than the erythrocyte, this effect may be responsible, at least in part, for the extrapancreatic effect of sulphonylureas, which seem to be of major importance for their hypoglycemic effect in noninsulin-dependent diabetic patients.

Blood Glucose↗
PubMed1983

Diurnal profile of pancreatic polypeptide, pancreatic glucagon, gut glucagon and insulin in human morbid obesity.

The diurnal profiles of pancreatic glucagon, insulin, pancreatic polypeptide (PP), and enteroglucagon were studied in five obese non-diabetic subjects (195 +/- 11 per cent of ideal body weight) and in six age matched controls. All the subjects were served with ordinary mixed meals five times during the day. The obese subjects were normoglycemic but hyperinsulinemic. Both groups showed rapid increases in PP to all meals, but the PP-response was significantly impaired in the obese group during the first part of the day. Normal subjects showed significant enteroglucagon responses to all meals, and had elevated levels throughout the day. In obese subjects, levels and responses were much lower at all times. Pancreatic glucagon profiles were similar. It is concluded that the possible role of abnormalities of PP and enteroglucagon secretion in the pathogenesis of human obesity deserves further study.

Adult↗
PubMed1982

Insulin receptor binding and insulin action in human fat cells: effects of obesity and fasting.

We have studied (125I)-insulin binding and insulin dose response relationships of (14C)-methylglucose transport conversion of (14C)-glucose to CO2 and total lipids, and lipolysis at 37 degrees C and pH 7.4 in adipocytes from obese patients before (n = 15) and after fasting for 10 days (n = 6). Studies of adipocytes from obese before fasting showed a significant reduction of insulin binding when expressed to cell surface area and rightward shifts of the insulin dose response curves (decreased insulin sensitivity) for glucose transport, glucose oxidation, lipogenesis and antilipolysis. The decreased insulin sensitivity of adipocytes from obese was most likely the functional consequence of the impaired insulin binding. Moreover, decreased maximal glucose transport capacities were present in rat cells from obese both in the basal and maximally insulin stimulated states. Similarly, the percentage response above basal level to maximal insulin stimulation of glucose oxidation and lipogenesis was impaired to these cells. The latter findings suggest post receptor defects localized both to the transport system per se and to intracellular mechanisms involved in the metabolism of glucose. Conversely, the post receptor pathways for the insulin induced antilipolysis was intact in fat cells from obese man. Studies after fasting showed an increase of adipocyte insulin binding accompanied by an increased sensitivity to the antilipolytic effect of insulin with unchanged maximal responsiveness. However, due to marked post receptor alterations, the insulin stimulated glucose utilization was severely blunted. Thus, the glucose transport system of adipocytes from all fasted subjects was totally unresponsive to insulin, while some of the fasted patients had a slight response of glucose oxidation and lipogenesis in the presence of insulin in maximally effective concentrations.

3-O-Methylglucose↗
PubMed1982

Circadian profiles of insulin receptors in insulin-dependent diabetics in usual and poor metabolic control.

We have characterized the 24-h changes of insulin receptors on erythrocytes from patients with insulin-dependent diabetes of long duration. These diabetics were studied both in usual and poor metabolic control. Moreover, we have examined daytime changes of insulin receptors on monocytes from newly discovered diabetics. In both erythrocyte and monocyte studies, diabetics were compared to healthy controls. At insulin tracer concentration, insulin receptor binding to erythrocytes from diabetics in usual control and normal volunteers underwent a statistically significant diurnal variation with high binding values in the early morning, low daytime values with a nadir in the late afternoon, and a peak around midnight. Even diabetics in poor metabolic control due to insulin deprivation had preserved a similar 24-h rhythm of erythrocyte insulin receptors. Insulin receptor binding to monocytes at insulin tracer concentration declined significantly during the day both in newly discovered diabetics and in healthy controls. The mechanisms responsible for the acute phase changes of insulin-receptor binding are unknown, but the receptor changes seem related to the fed state. Moreover, analysis of the temporal interrelationship between erythrocyte insulin binding and plasma insulin concentration in diabetics during the 24-h period suggests that in these patients insulin may be one of the factors determining the rapid insulin receptor regulation.

Adult↗
PubMed1982

Insulin binding and action on fat cells from young healthy females and males.

Insulin binding and action were studied in fat cells from the gluteal region of young healthy subjects. Fat cells from females were larger than those of males, had higher insulin receptor binding and higher rates of noninsulin-stimulated and maximally insulin-stimulated rates of methylglucose transport and glucose metabolism when these data were expressed per cell number. However, when insulin binding and insulin effects were expressed per cell surface, which may be physiologically more relevant, no sex differences were found in insulin binding and glucose transport, whereas noninsulin-stimulated and maximally insulin-stimulated glucose metabolism was still significantly increased in female fat cells. The latter indicates postreceptor differences in glucose metabolism between females and males. The insulin concentrations causing half-maximal responses (a measure of the sensitivity to insulin) of glucose transport, glucose metabolism and lipolysis were similar in fat cells from the two sexes, which is consistent with the comparable values of insulin receptor binding when adjusted to cell surface. Studies of rate-determining steps for the glucose utilization of human fat cells showed that glucose transport was not the rate-limiting step at physiological glucose concentrations. Moreover, at physiological glucose levels, glucose metabolism exhibited a decreased maximal insulin responsiveness and an increased insulin sensitivity when compared with glucose metabolism at low glucose concentrations at which glucose transport is rate limiting for the fat cell glucose utilization.

Adipose Tissue↗
PubMed1981

Hexose transport in human adipocytes: factors influencing the response to insulin and kinetics of methylglucose and glucose transport.

Optimal experimental conditions were defined for measuring the initial uptake rate of the non-metabolizable sugar analogue 3-O-methylglucose in non-stimulated and insulin-stimulated human adipocytes. The permeability of the adipocyte plasma membrane for tracer methylglucose (100 mumol/l) was 2.9 X 10(-7) cm X s-1 at 37 degrees C and slightly lower at 20 degrees C. At 37 degrees C and pH 7.4 insulin (5 nmol/l) increased the permeability about twofold (range 1.5 to fivefold) with half maximal effect at about 100 pmol/l). At pH 7.0 the dose response curve for the insulin effect on the uptake rate of methylglucose was shifted about 2.5-fold to the right. The permeability to L-glucose due to simple diffusion was estimated as 3.0 X 10(-10) cm X s-1 suggesting that uptake of methylglucose occurs almost exclusively by facilitated diffusion. The Km for methylglucose equilibrium exchange in insulin stimulated cells was about 4.8 mmol/l. The initial uptake of tracer methylglucose in insulin-stimulated cells was inhibited by unlabelled methylglucose and by D-glucose with inhibition constants of about 3.8 and 7.7 mmol/l respectively. Uptake of tracer 2-deoxyglucose (50 mumol/l) in insulin-stimulated adipocytes was linear from 10 s to 5 min whereas the rate of uptake in the presence of 3 mmol/l of D-glucose was markedly decreased suggesting that deoxyglucose uptake after a few minutes is mainly limited by hexokinase in the presence of glucose.

Adipose Tissue↗
PubMed1981

Monocyte-mediated antibody-dependent cytotoxicity. Modulation by Glycolysis and insulin.

In suspensions of purified human monocytes from 14 healthy persons the antibody-dependent cell-mediated cytotoxicity (ADCC), the lactate release, and the glucose uptake were studied. In non-stimulated monocytes ADCC correlated with lactate release and glucose uptake. Following addition of insulin a dose-related rise in ADCC, lactate release, and glucose uptake was observed. For each of the three processes the maximal insulin effect was about 30%. Most of the stimulation was seen within the physiological concentration range of insulin, and the insulin concentration resulting in 50% of the maximal effect was nearly the same for ADCC, lactate release, and glucose uptake (about 100 pM). The insulin stimulation of ADCC correlated with the stimulation of lactate release and glucose uptake. An inverse correlation between the ADCC of non-stimulated monocytes and the insulin stimulation of ADCC was demonstrated. No relationship was found between monocyte maturity and any of the three variables of monocyte function, either with or without insulin. These results indicate that, for normal monocytes, the cytotoxic capacity is closely related to the glycolysis.

Adult↗
PubMed1981

Decreased insulin binding to erythrocytes in subjects with Klinefelter's syndrome.

Insulin binding to specific erythrocyte receptors was investigated in group of 25 subjects with Klinefelter's syndrome (47 XXY genotype) and 14 healthy male volunteers. Insulin binding was significantly decreased in Klinefelter subjects (P less than 0.01 at insulin concentrations of 0.051 and 0.136 mmol/liter); however, their fasting glucose concentration was normal (87 +/- 17), and the glucose disappearance rate was slightly increased (2.3 +/- 0.9; P less than 0.2). These data indicated a compensatory, mechanism involved in the glucose metabolism in Klinefelter's syndrome.

Erythrocyte Membrane↗
PubMed1981

Insulin receptors in the pregnant diabetic and her newborn.

To ascertain if changes in the diabetic state during pregnancy were mediated by alterations in insulin receptors, we studied insulin receptors on monocytes and erythrocytes from 18 pregnant women with insulin-dependent diabetes (IDD) during the first and third trimesters. In the first trimester, insulin binding to both cell types was similar to that in normal nonpregnant women. Moreover, insulin receptor binding remained unchanged during the third trimester even in the face of the significantly increased insulin requirement and concomitant hyperinsulinemia. Our findings suggest that changes in insulin receptors are not primarily involved in alterations of diabetic control during pregnancy. Newborns of mothers with IDD have the appearance of fetal gigantism and often suffer from neonatal hypoglycemia. To determine whether altered insulin receptor binding might contribute to these phenomena, we studied insulin receptors on monocytes and erythrocytes in infants of normal mothers (n = 21) and mothers with IDD (n = 14). Compared to adults, insulin binding to both cell types from both categories of infants was significantly increased and to the same extent. The combination of fetal hyperinsulinemia and increased receptor binding in the presence of hyperglycemia may account, at least in part, for the accelerated growth of fetuses born of diabetic mothers. Finally, the enhanced neonatal glucose tolerance of these babies may be related not only to the hyperinsulinemia but also to increased insulin sensitivity mediated, in part, by the increased insulin receptor binding.

Erythrocytes↗
PubMed1981

Insulin receptor binding and receptor-mediated insulin degradation in human adipocytes.

UNLABELLED: 125I-insulin binding and receptor-mediated insulin degradation were studied in isolated human fat cells from subcutaneous tissue. A high albumin concentration during cell isolation and incubation protected the fragile human adipocyte from lysis. Binding of tracer was pH dependent with an optimum between 7.4 and 7.6. At 37 degrees C steady state was reached by 45 min and maintained for at least 2 h. The binding of labelled insulin in the presence of 10 mumol/l unlabelled insulin was only 1-4% of the total insulin binding. The half-maximal displacement of tracer iodoinsulin (10 pmol/l) by unlabelled insulin occurred at 0.25 nmol/l. Kinetic studies of the dissociation of labelled iodoinsulin from fat cells showed a slight acceleration in the presence of a high concentration of unlabelled insulin in the washout buffer as compared to a buffer containing no insulin. At steady state binding about 95% of the cell-associated radioactivity was extracted as iodoinsulin as judged by gel filtration. The remaining 5% co-eluted with iodotyrosine. During 60 min about 90% of the cell-associated radioactivity dissociated as iodoinsulin and the rest as iodotyrosine. CONCLUSIONS: 1) A high albumin content of buffers prevents traumatization of the human adipocyte; 2) under these conditions steady state binding of insulin is readily measured at 37 degrees C; 3) the use of a washing procedure makes the non-specific binding negligible; 4) the human adipocyte insulin receptor has a very high affinity; 5) receptor-mediated insulin degradation is minimal.

Adipose Tissue↗