Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whereas the expected decrease in the binding of 125I-insulin to erythrocytes 4.5 h after a standard mixed breakfast was seen in six young nonobese normoglycemic controls (delta % bound/free = 2.0 +/- 0.5 SEM), 10 obese hyperglycemic subjects showed an increase (0.54 +/- 0.43) and eight obese normoglycemic subjects of similar age and weight, no change in binding (0 +/- 0.31), both being significantly different from the controls (p less than 0.05) but not from each other. Of the total 18 obese subjects, the 11 with fasting hyperinsulinemia (23 +/- 1.4 mU/l) showed an increase in binding of 0.82 +/- 0.40, significantly different (p less than 0.05) from the decrease of 0.30 +/- 0.25 shown by the seven normoinsulinemic (11 +/- 1.4 mU/l) subjects, despite their similar age, weight, and blood glucose concentrations. These changes in binding were explained by alterations in receptor affinity. Thus, an anomalous postprandial increase in erythrocyte insulin receptor affinity occurs in some obese subjects with or without diabetes, and is related to hyperinsulinemia rather than hyperglycemia.
 ...
PMID:An anomalous postprandial increase in erythrocyte insulin receptor affinity associated with hyperinsulinemia. 351 May 26

We studied the effect of aerobic training and detraining on insulin-stimulated glucose disposal and on erythrocyte insulin receptor binding. Seven endurance-trained athletes were studied at 12 h, 60 h, and 7 days after cessation of training and compared with three untrained, age- and weight-matched controls. The metabolic clearance rate of glucose as measured by the euglycemic clamp technique was 15.6 +/- 1.8 ml/kg/min (mean +/- SEM) in the trained subjects 12 h after the last bout of exercise compared with 7.8 +/- 1.2 ml/kg/min in the untrained control group. When the trained subjects refrained from physical training, the metabolic clearance rate decreased to 10.1 +/- 1.0 ml/kg/min at 60 h and further to 8.5 +/- 0.5 ml/kg/min after 7 days of detraining. The percentage of specific insulin binding to young erythrocytes (density 1.089-1.092), isolated by density gradient centrifugation, decreased from 10.4 +/- 0.9 at 12 h after the last exercise to 8.1 +/- 0.7%/3 X 10(9) cells after 60 h of detraining (P less than 0.001). The decrease in insulin binding to erythrocytes was almost entirely accounted for by a decrease in the number of insulin receptors. We conclude that the increase in peripheral insulin action seen in trained athletes is rapidly reversed, possibly by a mechanism separate from other phenomena associated with chronic training. The parallel findings of decreased in vivo insulin action and decreased insulin binding in young erythrocytes suggest that modulation of in vivo insulin response by detraining may be at least partially mediated by changes in insulin receptor number.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Acute reversal of the enhanced insulin action in trained athletes. Association with insulin receptor changes. 389 19

Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disease characterized by progressive weakness and severe muscle wasting. Alterations in carbohydrate metabolism are often associated with neuromuscular disorders. We performed oral glucose tolerance tests and insulin binding studies on erythrocytes from 17 DMD and 8 normal males. Furthermore, we measured insulin binding to erythrocytes from 12 normal males and from 11 mothers and 10 sisters of affected males. As a group, DMD patients had mild glucose intolerance and both fasting and postabsorptive marked hyperinsulinemia (insulin resistance). Levels of glucose and insulin, expressed as incremental areas under their respective curves, were significantly elevated in the wheelchair-ridden patients. Incremental areas of glucose (0-2 h) and insulin (0-5 h) were 42 +/- 5 mg/dl X h (mean +/- SEM) and 96 +/- 18 microU/ml X h, respectively, in normal subjects and 71 +/- 6 (P less than 0.05) and 206 +/- 30 (P less than 0.05), respectively, in the wheelchair-confined DMD patients. All of the ambulatory DMD males had normal oral glucose tolerance tests. Insulin binding to erythrocytes was 20-30% lower (P less than 0.01) in all DMD patients than in normal males appropriately matched for age and degree of sexual development. This difference in binding was a result of lower affinity of the insulin receptor in DMD erythrocytes. On the other hand, insulin binding to fibroblasts was the same in normal males and DMD patients, suggesting that the abnormality of erythrocyte binding in DMD is probably not genetically induced. Insulin binding to erythrocytes and monocytes was the same in all females studied, regardless of whether they were carriers of the DMD gene. Our results suggest that abnormal insulin binding in DMD erythrocytes is an acquired rather than genetic abnormality, but insulin binding is not helpful in the identification of carrier females. The defect in insulin binding in DMD is present before the development of insulin resistance, which occurs only in severely immobilized patients. Thus, the cause of the insulin resistance in DMD may reside at steps beyond the binding of insulin to its receptor.
 ...
PMID:Dissociation of insulin resistance and decreased insulin receptor binding in Duchenne muscular dystrophy. 396 91

Previous investigations have demonstrated an increase in monocyte insulin receptor affinity two and five hours following oral carbohydrate loading. The present studies were undertaken to see if intravenous (IV) glucose challenge provokes a similar increase in monocyte insulin binding affinity. 25 grams of glucose were given to 10 lean normals and monocytes were isolated for 125I-insulin tracer binding studies (8.4 X 10(-10) M) at 0, 1 and 5 hours after glucose loading. The mean data show that monocytes develop a small, statistically insignificant increase in insulin-binding affinity one hour after intravenous glucose (mean +/- SEM, 7.28 +/- 1.06 ng/ml compared to basal 50% insulin displacement value, B50, of 9.25 +/- 1.62 ng/ml). B50 values demonstrated no increase in binding affinity at five hours (10.77 +/- 2.22 ng/ml). Prior studies have shown a 50 to 70% decrease in B50 following oral glucose, indicating a rapid increase in receptor binding affinity after carbohydrate ingestion. In contrast the present studies have shown that after IV glucose six normals had no decrease in B50 at one or five hours, while the remaining four normals had a 35% decrease at one hour but no decrease at five hours. Intravenous glucose loading, unlike an oral carbohydrate challenge, fails to provoke an acute, consistent increase in monocyte insulin binding affinity at these time points. Elevations in plasma glucose and insulin do not by themselves induce the acute increase in receptor affinity.
 ...
PMID:Intravenous glucose infusion fails to alter monocyte insulin-binding affinity in normal subjects. 404 27

The relative hypoglycemic effects of pulsatile versus steadily infused insulin have been examined in six normal subjects in whom pancreatic insulin output was suppressed by somatostatin-14. Soluble insulin was infused continuously overnight on one occasion and on another occasion the same quantity was given in pulses of 2-min duration with a gap of 11 min. The mean plasma glucose concentrations were lower when pulsed insulin was given [mean for the last hour: 4.66 +/- 0.08 mmol/L (+/- SEM) versus 5.53 +/- 0.06 mmol/L (+/- SEM) for steady infusion], diverging significantly (P less than 0.05 paired t test) 7 h after the start of the study. The specific binding of 125I(A14)mono-iodo-insulin to monocytes was greater after pulsed insulin (2.9% with pulsed versus 2.4% with steadily infused insulin at tracer-only point; P less than 0.02 paired t test). Thus, intravenous insulin has greater hypoglycemic effect when pulsed, possibly mediated by greater insulin receptor binding.
 ...
PMID:Pulsatile insulin has greater hypoglycemic effect than continuous delivery. 613 49

Insulin binding was studied in type II pneumocytes isolated from fetal rabbit lungs (27 days of gestation) and grown in monolayers in tissue culture. The mean high affinity receptor site number was 11.8 +/- 1.4 X 10(3) (+/-SEM)/cell, with a Kd of 0.45 +/- 0.07 nM (n = 6). Low affinity sites averaged 432 +/- 10.7 X 10(3)/cell, with a Kd of 45.6 +/- 11.8 nM. Incubation of the cells with 5 X 10(-10) M (Bu)2cAMP (DBcAMP) and 10(-3) M methylisobutylxanthine (MIX) for 18 h led to significant increases in the number of high affinity receptor sites and Kd (P = 0.025 and 0.05, respectively). Incubation of the cells with insulin (1 microgram/ml) for 18 h led to a significant diminution in the mean number of high affinity sites to 3.23 +/- 0.68 X 10(3)/cell (P = 0.0025). There was no significant change in the Kd of the high affinity sites. There was also no significant change in the number or affinity of the low affinity sites. When the cells were incubated with insulin in the presence of DBcAMP (5 X 10(-4) M) and MIX (10(-3) M), there was a significant increase in high affinity binding sites to a mean of 8.87 +/- 2.18 X 10(3)/cell (n = 4) compared to the value after incubation in the presence of insulin alone. There was no significant increase in the Kd of the high affinity sites. The following conclusions were drawn from these experiments. 1) Fetal type II pneumocytes possess receptors with high affinity for insulin. 2) The up-regulation of insulin receptor binding induced by high ambient concentrations of insulin in vivo in rabbit fetal lungs and circulating human monocytes does not occur in vitro when isolated pneumocytes are grown in tissue culture. 3) Insulin binding to type II pneumocytes is enhanced by DBcAMP and MIX. 4) Insulin down-regulation of receptor binding is significantly counteracted by DBcAMP and MIX.
 ...
PMID:Insulin receptors in fetal rabbit lung type II cells. 620 98

To gain insight into the mechanisms responsible for the impaired glycogenolytic response to glucagon and the diminished ketogenic capacity of newborn guinea pig, we studied the ontogeny of insulin and glucagon receptors, and the responsiveness of the adenylate cyclase complex to glucagon, PGE1, NaF, and cholera toxin in liver plasma membrane from fetal (58 d, late gestation, and 65 d, term) and adult guinea pigs. The number of insulin receptors (x 10(-10) M/L) was least in 58-d fetus (3.0 +/- 0.4; mean +/- SEM) and increased 3-fold in 65 d fetus (8.8 +/- 0.6; P less than 0.01). In adult guinea pig, both insulin receptor number (6.0 +/- 0.7) and average affinity constant (1.20 +/- 0.08 x 10(8) M-1) were significantly lower (P less than 0.01) compared with 65-d fetus. The number of glucagon receptors remained unchanged between 58-d and 65-d fetuses, but both average and high affinity association constants were significantly higher at d 65. In contrast to the lower capacity and affinity of insulin receptors in the adult compared with term fetus, the total glucagon receptor number (x 10(-10) M/L) in adults (7.2 +/- 0.8) was twice that of the 58 d (3.2 +/- 0.2) and 65 d (3.2 +/- 1.0) fetuses. The average affinity constant (x 10(8) M-1) in adult (3.8 +/- 0.2) was, however, significantly lower than the two fetal groups (58 d, 5.0 +/- 0.3; P less than 0.05 and 65 d, 8.1 +/- 1.0; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Ontogeny of insulin and glucagon receptors and the adenylate cyclase system in guinea pig liver. 633 Jun 58

This study investigates the effect of dialysis on the 24-hour insulin requirements in uraemic insulin dependent diabetic patients maintained at normoglycaemia using an artificial beta-cell. Five patients were studied twice, namely before initiation of dialysis treatment (mean 14 days) and after a mean of 46 days on chronic dialysis. The mean total diurnal insulin consumption was reduced significantly from 44.7 +/- 2.9 U (mean +/- SEM) before dialysis to 35.0 +/- 2.3 U after dialysis therapy (p less than 0.01). The reduction included the prandial as well as the basal insulin requirements (p less than 0.02). It is most likely that an insulin receptor or a post-receptor defect account for the insulin insensitivity present in uraemia. Our study demonstrates that this defect is at least partly reversible after dialysis treatment.
 ...
PMID:Effect of haemodialysis on insulin requirements in uraemic diabetic patients. Studies with the artificial beta-cell. 634 66

In order to evaluate the in vivo effects of biguanides on the insulin receptor, we have studied insulin binding to circulating monocytes of six normal controls, eight obese nondiabetic subjects, and six obese type II diabetic patients, both before and after 4 days of treatment with the biguanide metformin (850 mg twice daily orally). Before drug administration, 125I-insulin binding to monocytes was decreased in obese subjects and diabetic patients. After metformin administration, an increase in insulin binding to peripheral monocytes was observed in seven of eight obese nondiabetic subjects (3.57 +/- 0.43 to 4.69 +/- 0.59% bound at 10(7) monocytes, mean +/- SEM, P less than 0.01) and in all diabetic patients (3.21 +/- 0.21 to 5.22 +/- 0.34, P less than 0.01). Scatchard plots indicated that the increased binding was due to an increase in the receptor number. In contrast, no significant change in insulin binding was found in normal controls after metformin administration (5.31 +/- 0.14 and 4.70 +/- 0.12). These studies indicate that metformin normalizes the binding of insulin to its receptor in obese subjects and diabetic patients. It is suggested, therefore, that the action of metformin on the insulin receptor may be one of the mechanisms of the antidiabetic effect of this drug.
 ...
PMID:Metformin normalizes insulin binding to monocytes from obese nondiabetic subjects and obese type II diabetic patients. 635 Mar 37

To determine the influence of insulin infusions used in dose-response studies on monocyte insulin binding, monocyte insulin binding and glucose disposal were measured in six normal subjects before and at the end of each of four sequential 2-h insulin infusions (0.4, 1.0, 2.0, and 10 mU kg-1 min-1). Monocyte insulin binding was unaltered at the end of the first three infusions (plasma insulin, 31 +/- 2 (SEM), 77 +/- 3, and 184 +/- 10 microU/ml) but was decreased after the last infusion (plasma insulin, 1730 +/- 125 microU/ml) at 0.2 through 10.2 ng/ml insulin concentrations in the binding assay (P less than 0.01). Using a one-site model, this could be ascribed to a decrease in insulin receptor affinity (1.54 +/- 0.26 vs. 2.27 +/- 0.48 X 10(8) M-1, P less than 0.05), whereas in a two-site model this appeared to be due to a decrease in high affinity binding sites (1,868 +/- 228 vs. 2,387 +/- 207, P less than 0.02). Nevertheless, insulin receptor occupancies estimated to occur during the insulin infusions were virtually identical whether preinsulin infusion binding data (745 +/- 72, 1,383 +/- 117, 2,572 +/- 302, and 10,092 +/- 1,708) or binding data at the end of each infusion (702 +/- 56, 1,367 +/- 150, 2,383 +/- 318, and 9,158 +/- 2,023) were used to calculate occupancy. These results indicate that although monocyte insulin binding decreased during dose-response experiments using sequential infusions of insulin, due to the concentrations of insulin at which this occurs this decrease did not alter the shape of the dose-response curve relating glucose disposal to monocyte insulin receptor occupancy.
 ...
PMID:Influence of changes in insulin receptor binding during insulin infusions on the shape of the insulin dose-response curve for glucose disposal in man. 636 38


<< Previous 1 2 3 4 5 Next >>