THE INSULIN RECEPTOR IN NORMAL AND OBESE PERSONS

1976 ◽  
Vol 83 (3) ◽  
pp. 565-575 ◽  
Author(s):  
Henning Beck-Nielsen ◽  
Oluf Pedersen ◽  
Jens Peder Bagger ◽  
Niels Schwartz Sørensen

ABSTRACT Using [125I]insulin at 172 pmol/l (1 ng/ml) the binding of insulin to mononuclear leucocytes isolated from peripheral blood was studied. Our present study comprised 21 healthy subjects (22–33 years old, 90–110% of ideal weight) and a comparable group of 22 obese subjects (20–37 years old, minimum 150% of ideal weight). A significant difference in insulin binding was found between the two groups, the mean specific insulin binding fraction in normals being 1.92 ± 0.58 (s) × 10−2 and that for the obese 1.19 ± 0.41 (s) × 10−2 (P < 0.01). No correlation was found between body weight and the number of insulin receptors in the obese subjects. However, the number of insulin receptors was negatively correlated to fat cell size (P < 0.05). Insulin receptors in subjects were also negatively correlated to fasting plasma insulin (P < 0.05). Insulin receptors were studied in 11 obese subjects before and after 10 days of fasting. A significant increase in the number of insulin receptors was observed with a simultaneous decrease in plasma insulin to normal values. The results indicate that obesity complicated by hyperinsulinism is associated with a decrease in the number of insulin receptors compared with the normal. This finding may in part explain the decreased insulin sensitivity of the hyperinsulinaemic obese.

1976 ◽  
Vol 83 (3) ◽  
pp. 556-564 ◽  
Author(s):  
Oluf Pedersen ◽  
Henning Beck-Nielsen

ABSTRACT Insulin binding sites were demonstrated in human mononuclear leucocytes by use of a technique which includes isolation of mononuclear leucocytes from defibrinated blood and separation of cell bound and free [125I] insulin with silicone oil. The binding was time and temperature dependent. At 15°C equilibrium was reached after 90 min and a plateau maintained for at least 50 min. Incubations were carried out at 4°C, 15°C and 37°C. Maximal binding was obtained at 15°C. The optimum pH for insulin receptor interaction occurred at about 8. [125I] insulin binding to mononuclear leucocytes was demonstrated to be a linear function of cell number concentration over a range of 17–70× 106×ml−1. The binding was a displaceable function of native insulin concentration. In a group of 21 young healthy persons with normal body weight we found a mean specific cell binding fraction of 1.92 ± 0.58 (s) × 10−2. Analysis of the equilibrium between insulin and its receptor revealed an apparent heterogeneity of insulin receptors.


1980 ◽  
Vol 186 (2) ◽  
pp. 535-540 ◽  
Author(s):  
S Clark ◽  
R G Larkins ◽  
M De Luise ◽  
R A Melick

The effect of alterations to the insulin receptor on the insulin sensitivity of isolated adipocytes was studied. Receptor changes were induced by treatment of adipocytes with either phospholipase C or trypsin. After enzyme treatment, binding of insulin to insulin receptors and insulin-mediated glucose metabolism were examined. Exposure of adipocytes to phospholipase C (2 units/ml) significantly increased insulin binding to the cells, but destroyed the ability of the cells to oxidize glucose. After treatment with trypsin (500 micrograms/ml) for 5 min, insulin binding to the adipocytes was significantly increased. This was shown to be due to an increase in insulin-receptor affinity. Metabolic studies showed that trypsin treatment led to an increase in basal glucose transport but markedly decreased the response to insulin at all concentrations tested. Adipocytes treated with trypsin showed no significant difference in basal glucose oxidation rates when compared with controls, but were less sensitive to insulin at low insulin concentrations, and showed a decreased maximum response at high insulin concentrations. In conclusion, these findings indicate a dissociation between induced changes in binding of insulin to insulin receptors and subsequent hormone action. The importance of post-receptor events in the biological action of insulin is highlighted.


1994 ◽  
Vol 266 (2) ◽  
pp. E155-E160
Author(s):  
R. R. Townsend ◽  
S. Klein ◽  
R. R. Wolfe

The lipolytic response to epinephrine is increased in lean but not obese subjects during conditions of increased circulating catecholamines such as starvation and critical illness. We evaluated the effect of repeated epinephrine treatment (0.03 micrograms.kg-1.min-1 for 30 min thrice daily) on basal lipolysis and the lipolytic response to epinephrine in lean and obese subjects. Lipolytic rates were determined using [2H5]glycerol during basal conditions and 60 min of epinephrine infusion before and after 6 days of repeated epinephrine treatment. Basal lipolysis and the lipolytic response to epinephrine were higher in obese (2.47 +/- 0.51 mumol.kg-1.min-1 and 106 +/- 21 mumol/kg, respectively) than lean (1.45 +/- 0.15 mumol.kg-1.min-1 and 70 +/- 12 mumol/kg, respectively; P = 0.08 obese vs. lean) subjects. Repeated epinephrine treatment decreased basal glycerol rate of appearance and the lipolytic response to epinephrine in lean and obese subjects. Plasma insulin concentration increased after repeated epinephrine treatment in both obese (14.3 +/- 0.6 to 18.2 +/- 1.6 microU/ml; P < 0.05) and lean (8.4 +/- 1.3 to 11.1 +/- 1.5 microU/ml; P < 0.01) subjects. Repeated epinephrine treatment suppresses basal and epinephrine-stimulated lipolysis. Increased plasma insulin concentration may be the mechanism.


1979 ◽  
Vol 90 (3) ◽  
pp. 451-462 ◽  
Author(s):  
Henning Beck-Nielsen ◽  
Oluf Pedersen ◽  
Hans Otto Lindskov

ABSTRACT 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 > 0.1). However, the insulin sensitivity increased 37 % (P < 0.01). Furthermore, the insulin binding to monocytes increased (P < 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 > 0.1). The insulin sensitivity, however, increased 83% (P < 0.01). Moreover, the insulin binding was raised (P < 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 < 0.05) 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.


1983 ◽  
Vol 61 (8) ◽  
pp. 802-807 ◽  
Author(s):  
C. Martin ◽  
K. S. Desai ◽  
G. Steiner

We examined the effects of inducing hyperinsuiinemia in vivo in rats on the insulin receptors of, and the glucose oxidation by their adipocytes. Hyperinsulinemia was induced over a 2-week period by injecting NPH insulin subcutaneously. This was given in doses that were gradually increased to a final dose of 6 units/day. Profound hypoglycemia was avoided by providing supplemental sucrose to both the insulin-treated and control rats. The insulin concentration was eight times greater in the insulin-treated rats. However, they were not grossly obese and their adipocytes were not enlarged. The adipocytes of the hyperinsulinemic rats had a 25% lower maximal insulin binding capacity and were resistant to the effects of insulin on glucose oxidation. We felt that the hyperinsuiinemia was sufficient so that, despite their somewhat lower insulin binding capacity, these adipocytes would not bind less insulin in vivo than would adipocytes from control rats. Hence, we postulated that, this massive hyperinsulinemia not only down regulated the insulin receptor, but also led to a postreceptor resistance. This notion was supported by two lines of in vitro data. First, even at maximally effective medium concentrations of insulin, the maximum rate of glucose oxidation by the adipocytes from hyperinsulinemic rats reached a plateau which was less than that reached by cells from controls. Second, when this in vitro glucose oxidation was related not merely to the medium insulin concentration, but to the amount of insulin bound to adipocytes, the response of the hyperinsulinemic rats' cells was always lower than control. These changes occurred in the absence of any difference in fat cell size. Thus, in vivo hyperinsulinemia led to insulin resistance in adipocytes. This was associated both with down regulation of the insulin receptors and with a postreceptor defect.


1987 ◽  
Vol 57 (03) ◽  
pp. 326-328 ◽  
Author(s):  
Ph Vague ◽  
I Juhan-Vague ◽  
M C Alessi ◽  
C Badier ◽  
J Valadier

SummaryWe have previously observed a positive correlation between Plasminogen Activator Inhibition capacity (PA Inhibition), Body Mass Index (BMI) and plasma insulin levels in a population of non diabetic subjects. The anti diabetic biguanide Metformin which decreases insulin resistance has been reported to increase the blood fibrinolytic activity. Therefore we have studied the effect of Metformin on PA Inhibition levels in obese subjects with normal glucose tolerance. Eighteen obese women (O) (BMI: 31.4 ± 1.13, m ± S.E.M.) were compared to age matched controls (C) (BMI: 20.2 ± 0.8) and randomized to a 15 days treatment by Metformin (M) (1.7 g/day) or placebo (P) in a double blind study while on a weight maintaining diet. O compared to C had higher levels (m ± S.E.M.) of PA Inhibition (9 ± 1.8 IU/ml, versus 2.88 ± 0.29 p <0.01), lower euglobulin fibrinolytic activity (EFA) (4.95 ±1.17 mm versus 9 ± 0.29 p <0.05), higher plasma insulin (24.1 ±2.1. uU/ml), versus 12 ± 1 p <0.01) and triglyceride (1.32 ± 0.16 mmol/1, versus 0.8 ± 0.08 p <0.05). After 15 days of treatment, in group M a significant decrease in PA Inhibition (5.51 ± 1.4, versus 9.48 ±2.1 p <0.05) in plasma insulin (18.5 ±0.1, versus 24.5 ± 3.5, p <0.05) and plasma triglyceride (1.08 ± 0.1, versus 1.47 ± 0.3 p <0.05) and an increase in EFA (6.50 ± 0.28, versus 5.25 ± 0.35 p <0.05) were observed. No significant variation was observed in group P.


Author(s):  
A. E. Chernikova ◽  
Yu. P. Potekhina

Introduction. An osteopathic examination determines the rate, the amplitude and the strength of the main rhythms (cardiac, respiratory and cranial). However, there are relatively few studies in the available literature dedicated to the influence of osteopathic correction (OC) on the characteristics of these rhythms.Goal of research — to study the influence of OC on the rate characteristics of various rhythms of the human body.Materials and methods. 88 adult osteopathic patients aged from 18 to 81 years were examined, among them 30 men and 58 women. All patients received general osteopathic examination. The rate of the cranial rhythm (RCR), respiratory rate (RR) heart rate (HR), the mobility of the nervous processes (MNP) and the connective tissue mobility (CTM) were assessed before and after the OC session.Results. Since age varied greatly in the examined group, a correlation analysis of age-related changes of the assessed rhythms was carried out. Only the CTM correlated with age (r=–0,28; p<0,05) in a statistically significant way. The rank dispersion analysis of Kruskal–Wallis also showed statistically significant difference in this indicator in different age groups (p=0,043). With the increase of years, the CTM decreases gradually. After the OC, the CTM, increased in a statistically significant way (p<0,0001). The RCR varied from 5 to 12 cycles/min in the examined group, which corresponded to the norm. After the OC, the RCR has increased in a statistically significant way (p<0,0001), the MNP has also increased (p<0,0001). The initial heart rate in the subjects varied from 56 to 94 beats/min, and in 15 % it exceeded the norm. After the OC the heart rate corresponded to the norm in all patients. The heart rate and the respiratory rate significantly decreased after the OC (р<0,0001).Conclusion. The described biorhythm changes after the OC session may be indicative of the improvement of the nervous regulation, of the normalization of the autonomic balance, of the improvement of the biomechanical properties of body tissues and of the increase of their mobility. The assessed parameters can be measured quickly without any additional equipment and can be used in order to study the results of the OC.


1963 ◽  
Vol 42 (3) ◽  
pp. 437-452 ◽  
Author(s):  
H. Daweke

Using the method of glucose-1-14C oxydation to 14CO2 on the rat epididymal adipose tissue, the insulin-like activities (ILA) in the serum have been compared before and after oral loading with glucose in normal subjects, in maturity-onset diabetics and in insulin-requiring diabetics. In maturity-onset diabetics mean fasting values were found to be 30% below normal while in insulin-requiring diabetics they were 85% above normal. In normal subjects there was observed, 30 minutes after glucose loading, a moderate increase in blood sugar together with an increase of ILA of 222% above the starting value; in maturity-onset diabetics the increase in ILA was only 106% while the blood sugar was markedly increased. After glucose loading in maturity-onset diabetics, the total amount of insulin detected during the period of the experiment was, on the average, only 45% of that found in normal subjects. In insulin requiring diabetics there was no increase but, on the contrary, a steady decrease of the ILA values, while the blood sugar excessively increased. In general ILA values were higher than those in maturity-onset diabetics. No difference in response was found between maturity-onset diabetics treated with diet alone and those treated with diet and oral hypoglycaemic drugs. In contrast to the absolute ILA values, the index of insulin reserve, is of value in assessing the functional capacity of the pancreas. This index decreases progressively with the severity of the disease and reaches a maximum of 54% of the normal in maturity-onset diabetics, which can satisfactorily be explained by pancreas insufficiency. Only in some cases of insulin-requiring diabetics was an insulin reserve still detectable. The biological inactivity of the insulin circulating in the blood can be deduced from the increased ILA-values, as compared with those found in maturity-onset diabetics. Obviously some of this insulin can be released by the addition of glucose. It is likely that, in addition to pancreatic insufficiency, insulin-binding or insulin-inactivating antibodies play a part in the pathogenesis of insulin-requiring diabetes.


2018 ◽  
Vol 1 ◽  
pp. 107
Author(s):  
Adi Heryadi ◽  
Evianawati Evianawati

This study aims to prove whether transformational leadership training is effective for building anti-corruption attitudes of villages in Kebonharjo village, subdistrict Samigaluh Kulonprogo. This research is an experimental research with one group pre and posttest design.Subject design is 17 people from village of 21 candidates registered. Measuring tool used in this research is the scale of anti-corruption perception made by the researcher referring to the 9 anti-corruption values with the value of reliability coefficient of 0.871. The module used as an intervention made by the researcher refers to the transformational leadership dimension (Bass, 1990). The data collected is analyzed by statistical analysis of different test Paired Sample Test. Initial data collection results obtained sign value of 0.770 which means> 0.05 or no significant difference between anti-corruption perception score between before and after training. After a period of less than 1 (one) month then conducted again the measurement of follow-up of the study subjects in the measurement again using the scale of anti-corruption perception. The results of the second data collection were analysed with Paired Samples Test and obtained the value of 0.623 sign meaning p> 0.05 or no significant difference between post test data with follow-up data so that the hypothesis of this study was rejected.


Author(s):  
Sanjeeva Kumar Goud T ◽  
Rahul Kunkulol

The present study was aimed to study the effect of Sublingual Vitamin D3 on Serum Vitamin D level in Vitamin D deficiency patients. This was a cross-sectional and interventional study. All the Vitamin D deficiency patients of age 18-60years and either gender, willing to participate in the study were included. Patients who had greater than 20 ng/ml were excluded from the study. The total number of participants in our study was 200, out of these 111 males and 89 females, the mean age in our study was 51.07 ± 7.39Yrs. All volunteers were given sublingual vitamin D3 (60,000IU) in six doses every fifteen days of follow up for 3 months. The subject’s serum 25(OH)D levels were estimated before and after the treatment of sublingual vitamin D3. There was a statistically significant difference in serum vitamin D3 level before 16.61±6.71 ng/ml and after 35.80±7.80 ng/ml after treatment with Sublingual Vitamin D3. Six doses of 60,000IU of Vitamin D3 sublingual route having improved the role of serum 25(OH)D levels in the treatment of Vitamin D3 deficiency patients.Keywords: Vitamin D3; Sublingual route


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