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Biomedical subjects

O Pedersen

Publications and source records attributed to O Pedersen.

At least 271 records · Page 15Linked to original sources

Increased insulin receptors after exercise in patients with insulin-dependent diabetes mellitus.

Physical exercise is known to improve glucose tolerance and diminish insulin requirements in patients with well-controlled diabetes mellitus. To ascertain whether these effects of exercise are associated with alterations in insulin receptors, we studied [125I]insulin binding to erythrocytes and monocytes in athletically untrained young men with insulin-treated diabetes during three hours of postprandial bicycle exercise (nine patients) and two hours of exercise during fasting (eight patients). Compared with control periods, postprandial exercise, as well as exercise during fasting, significantly increased insulin binding to erythrocytes and monocytes at an insulin-tracer concentration of 34 pmol per liter. We suggest that similar changes occur in working muscle cells and contribute to the improved glucose tolerance induced by exercise.

Adult↗

Effects of dietary changes on cellular insulin binding and in vivo insulin sensitivity.

The effect of a low-sucrose, low-fat diet on insulin sensitivity, insulin binding to monocytes, and insulin secretion in nonketotic diabetic patients was studied. Ten obese diabetics were studied for 1 yr before and during treatment with a 1200-1500-kcal diet, whereas six diabetics of normal weight were studied for 3 mo before and after treatment with a 2200-2400-kcal diet. In the obese group, no change was found in the insulin response to i.v. injection of glucose during treatment (p greater than 0.1), but the insulin sensitivity was normalized after 1 yr (p less than 0.01). The clinical normalization and the improvement of insulin sensitivity were accompanied by a parallel normalization of the binding of insulin to monocytes (p less than 0.01). In the group of normal-weight diabetics, both the insulin sensitivity (p less than 0.05) and the insulin binding to monocytes (p less than 0.05) were normalized after a 3-mo treatment period, but the insulin secretion increased (p less than 0.05) without reaching normal values. We conclude that most nonketotic diabetic patients can be controlled by diet treatment alone. The mechanism of action of the low-fat, low-sucrose diet seems for the greatest part to be a normalization of the insulin sensitivity, which is partly caused by a normalization of the cellular insulin binding.

Adult↗

Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects.

We have studied whether the sucrose-induced reduction of insulin sensitivity and cellular insulin binding in normal man is related to the fructose or the glucose moiety. Seven young healthy subjects were fed their usual diets plus 1000 kcal extra glucose per day and eight young healthy subjects were fed their usual diets with addition of 1000 kcal extra fructose per day. The dietary regimens continued for 1 week. Before change of diet there were no statistically significant differences between body weight and fasting plasma concentrations of glucose, insulin, and ketone bodies in the two groups studied. High-glucose feeding caused no significant changes in insulin binding or insulin sensitivity whereas high-fructose feeding was accompanied by a significant reduction both of insulin binding (P less than 0.05) and insulin sensitivity (P less than 0.05). The changes in insulin binding and insulin sensitivity correlated linearly (r = 0.52, P less than 0.01). We conclude that fructose seems to be responsible for the impaired insulin binding and insulin sensitivity induced by sucrose.

Adult↗

Prednisone increases the number of insulin receptors on monocytes from normal subjects.

The effect of prednisone on insulin receptors on circulating monocytes was studied in 38 normal volunteers. Intake of prednisone in doses which are usually employed in clinical treatment (40 mg/day) was associated with a significant increase int the number of insulin receptors. The rise in insulin binding was maximal 7 h after the begining of the medication and it was dose related.

Adult↗

Decreased insulin binding to monocytes from normal pregnant women.

To ascertain whether the decrease of glucose tolerance in pregnancy might be mediated by changes in insulin receptors, we have studied insulin binding to monocytes in 12 normal women during late pregnancy and 14 healthy, young, normal weight, nonpregnant female controls. The pregnant women had significantly higher fasting insulin concentrations in plasma than the controsl (18 +/- 3.5 vs. 8 +/- 1.1 microU/ml; P less than 0.01). Fasting concentrations of glucose and ketone bodies in plasma were not significantly different in the two groups. Insulin binding to monocytes from pregnant women was about 35% lower at each insulin concentration tested compared to the nonpregnant controls (P less than 0.01 at tracer insulin concentrations). Changes in cellular insulin binding were due to changes of the receptor number per cell, whereas the receptor affinity was unaffected. Insulin binding was not significantly correlated with the fasting plasma insulin in either of the two groups (P less than 0.1). Our results suggest that the deterioration of glucose tolerance in normal late pregnancy might be explained by a decrease of insulin sensitivity caused by a reduction of the number of insulin receptors.

Adult↗

Normalization of the insulin sensitivity and the cellular insulin binding during treatment of obese diabetics for one year.

The relative importance of the insulin resistance, the decreased cellular insulin binding and the relative insulin deficiency in the pathogenesis of diabetes mellitus in obese subjects has been studied. Ten obese diabetics were studied before and during treatment for 1 year with a 1200-1500 kcal's diet. No change was found in the insulin response to iv injection of glucose during treatment (P greater than 0.1), whereas the insulin sensitivity was normalized after 1 year (P less than 0.01). In parallel to the clinical normalization and the improvement of the insulin sensitivity the insulin binding to monocytes was normalized (P less than 0.01). We conclude that both the insulin resistance and the relative insulin deficiency are of decisive importance in the pathogenesis of diabetes mellitus of the obese. The insulin receptor defect seems to be one of the major factors responsible for the insulin resistance.

Adult↗

Increased insulin sensitivity and cellular insulin binding in obese diabetics following treatment with glibenclamide.

The aim of the present study was to examine the effect of glibenclamide on the insulin receptors, the insulin sensitivity and the insulin secretion in obese non-ketotic diabetics. Two groups of 9 obese diabetics were studied before and after 10 days' treatment with a 1200 kcal's diet and a 1200 kcal's diet + 10 mg/day of glibenclamide, respectively. In the group treated with diet alone we found no significant alteration of the insulin secretion pattern (P greater than 0.1). However, the insulin sensitivity increased 37% (P less than 0.01). Furthermore, the insulin binding to monocytes increased (P less than 0.01) due to a 36% rise of the binding affinity. In the group treated with glibenclamide and diet the insulin secretory pattern was unchanged, too (p greater than 0.1). The insulin sensitivity, however, increased 83% (P less than 0.01). Moreover, the insulin binding was raised (P less than 0.01) as a result of a 80% rise of the number of insulin receptors. In 4 patients who were treated with diet (1200 kcal/day) plus glibenclamide and in 5 patients who were treated with diet alone (1200 kcal/day) the insulin binding to monocytes was studied during treatment for 1 year. After 1 year we found a significantly (P less than 0.005) higher cellular insulin binding in the glibenclamide treated patients compared to the patients who got diet alone. We conclude that 1) the augmentation of the insulin sensitivity is of great importance for the normalization of the diabetic state in obese, 2) the increase in insulin binding may be of importance for the increase in insulin sensitivity, 3) glibenclamide appears to enhance the insulin sensitivity through an increase in the number of insulin receptors.

Adult↗

Insulin receptors on monocytes of young healthy persons correlated with glucose tolerance and insulin sensitivity.

We have studied in normal man the interrelationships between insulin binding to monocytes, glucose tolerance and insulin sensitivity. In 25 young healthy persons we found a significant positive correlation between insulin binding and glucose disappearance rate both after glucose (R = 0.68, p less than 0.001) and insulin (R = 0.49, p less than 0.02) given intravenously.

Adult↗

Diurnal variation in insulin binding to human monocytes.

We studied insulin binding to monocytes isolated from dieting and fasting young healthy persons during a 24-h period. In the persons who ate their usual food, we found a characteristic diurnal variation in the cellular insulin binding. Daytime insulin binding was low with a minimum in the afternoon; binding increased during the evening, reaching a maximum in the early morning. This variation seemed to be diet related, as total fasting abolished the circadian rhythm. Changes in cellular insulin binding were due to fluctuations in the binding affinity rather than alterations in receptor concentration. The circadian variation in insulin binding was grossly parallel to the well known variations in insulin sensitivity and glucose tolerance during the day.

Adult↗

Decreased binding of insulin to its receptor in patients with congenital generalized lipodystrophy.

Patients with congenital generalized lipodystrophy are extremely insulin resistant. To ascertain whether this resistance is due to an insulin receptor defect, we tested four young patients with congenital generalized lipodystrophy and seven healthy persons of comparable age for the binding of 125I insulin to mononuclear leukocytes isolated from peripheral blood. Mononuclear leukocytes from patients with congenital generalized lipodystrophy bound significantly less insulin than cells from normal subjects (P less than 0.01). When patients with lipodystrophy fasted for 60 hours, the insulin binding increased. Altered insulin receptors may be responsible for the pronounced insulin resistance and the decreased synthesis of triglycerides in congenital generalized lipodystrophy.

Adolescent↗

The monocyte as a model for the study of insulin receptors in man.

We have characterized the cellular composition of preparations isolated from peripheral blood by Ficoll-Isopaque gradient centrifugation. 125I-insulin binding to every cell type was measured. A highly significantly positive correlation between specific cell binding fraction and the monocyte concentration of the heterogeneous cell suspension was demonstrated. Depletion of monocytes reduced the insulin binding approximately 80%, which confirms previous findings by other investigators. The granulocytes possessed the second highest binding ability, but only one fourteenth of that of monocytes. Compared to the lymphocyte the monocyte had about 25 times greater insulin binding. Also thrombocytes bound insulin and contamination with these meant that their contribution to the total specific cell binding was not negligible. A reduction in these contaminants is essential. We found that insulin binding to erythrocytes was insignificant. A method of calculating the specific insulin binding to monocytes alone is introduced. The monocyte-insulin-receptor possesses specificity. Only an insignificant degradation of receptor bound insulin could be shown. Evidence of negative cooperativity between receptors was found. Consequently monocytes are considered a useful model for insulin receptor studies in man.

Binding, Competitive↗

Role of bran in normals. Serum levels of cholesterols, triglyceride, calcium and total 3 alpha-hydroxycholanic acid, and intestinal transit time.

After the intake of approximately 24 g wheat bran daily for 5 weeks, 25 trainee nurses showed no changes in the serum levels of cholesterol, triglyceride, calcium or total 3 alpha-hydroxycholanic acid. On the other hand, the study revealed a reduced intestinal transit time with good correlation to an increased frequency of bowel movements. Average body weight fell significantly, by 0.4 kg. The daily caloric intake remained constant throughout the study period, whereas the calcium intake was significantly increased. Among the serum parameters and the dietary constituents, good correlation was found only between serum cholesterol and the dietary cholesterol content. In addition, an inverse relationship was demonstrated between the serum levels of cholesterol and total 3 alpha-hydroxycholanic acid. The significance of this observation is as yet unknown.

Adult↗