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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic osteopenia has been known as one of the chronic complications of diabetes mellitus, and a decrease in bone turnover has been thought to be one of the pathophysiological characteristics of this complication. In order to investigate the effect of long-term insulin therapy on low bone turnover in diabetes, pancreas transplantation was performed on streptozotocin-induced diabetic rats. Plasma levels of bone gamma-carboxyglutamic acid-containing protein(osteocalcin) in untreated diabetic rats were 0.9 +/- 0.1 (mean +/- SEM) nmol/l, significantly lower than the value of 4.2 +/- 0.6 nmol/l in control rats (p less than 0.01). Pancreas transplantation reversed this decrease to 6.3 +/- 1.1 nmol/l, which was not significantly different from the value in control rats. The circulating levels of calcitriol were significantly decreased in the untreated diabetic group (p less than 0.01), and the decrease was fully reversed by pancreas transplantation. In addition, the decreases in bone length, strength and weight were also improved by the transplantation. This evidence clearly shows that the improvement of metabolic derangements in diabetes by insulin is essential for the prevention of deterioration in diabetic osteopenia. It is possible, therefore, that insulin exerts an indirect beneficial influence through the metabolic amelioration on the decreases in bone turnover and circulating osteocalcin in diabetes mellitus, or has a direct stimulatory effect on the osteoblasts via the insulin receptor since its presence has been shown recently in osteoblastic cells.
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PMID:Effect of pancreas transplantation on decreased levels of circulating bone gamma-carboxyglutamic acid-containing protein and osteopenia in rats with streptozotocin-induced diabetes. 138 56

The effects of high glucose and insulin concentrations on fetal lung insulin receptors and tyrosine kinase activity were studied in an in vitro system utilizing 19- or 20-d fetal rat lung explants. Exposure of the explants to 100 mM glucose and insulin (0.1 unit/mL) for 72 h resulted in a significant decrease in specific binding of insulin to partially purified receptors [5.78% +/- 0.66 (SEM) vs. 9.64% +/- 1.68; P less than .01] when compared with lung explants exposed to 10 mM glucose alone. When individual effects of high insulin and glucose were studied, down-regulation of specific insulin binding was also observed, but to a lesser extent than that observed using both high glucose and insulin. Differences in insulin receptor affinity were not noted. Insulin receptor tyrosine kinase activity was also significantly decreased (52% of control values) under high-glucose/high-insulin conditions. Total phosphatidylcholine and disaturated phosphatidylcholine concentrations were significantly decreased in explants grown under high-glucose/high-insulin conditions, consistent with delayed pulmonary maturation. High glucose and insulin levels thus result in down-regulation of fetal lung insulin receptors and insulin receptor tyrosine kinase activity late in gestation. These results may have implications for substrate availability in the developing fetal lung.
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PMID:Effects of insulin and glucose on pulmonary insulin receptors in late gestation fetal rats. 157 32

The insulin resistance in newborn mammals may be caused by a receptor or postreceptor defect. Although liver and umbilical cord blood monocytes have increased numbers of insulin receptors, there is a paucity of information about other neonatal tissues. Glucose disposal takes place primarily in the skeletal muscle; therefore, it is important to evaluate this tissue for an insulin receptor defect. To determine the role of insulin receptors in neonatal insulin resistance, neonatal and adult canine skeletal muscle, heart, and liver were compared for numbers of insulin receptors and their affinity for insulin. Partially purified receptors from four animals in each group were obtained by wheat germ lectin affinity chromatography and used in competition binding studies. Specific binding (mean +/- SE) in the absence of cold insulin was increased in newborn skeletal muscle (9.7 +/- 0.8 versus 4.8 +/- 0.5%, p less than 0.001) and heart (8.1 +/- 1.2 versus 5.5 +/- 0.6%, p less than 0.05). High-affinity insulin receptor number (mean +/- SEM) was increased in newborn skeletal muscle (183 +/- 40 versus 120 +/- 29 pM, p less than 0.002) and heart (264 +/- 94 versus 157 +/- 51 pM, p less than 0.05) as estimated from the X intercept of the Scatchard plot. Using half-maximal binding to estimate affinity, there were no differences between adults and newborns among all tissues studied. High-affinity receptor number and percentage of specific binding were similar for newborn and adult liver tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin receptor number and binding affinity in newborn dogs. 186 18

Erythrocyte insulin receptor binding measurements were evaluated in 8 dogs with spontaneous hyperadrenocorticism. These dogs had normal serum glucose concentration, with normal to high serum insulin concentration (range, 45 to 1,400 pmol/L; normal, 40 to 170 pmol/L). Dogs with hyperadrenocorticism had significant (P less than 0.01) decrease in mean +/- SEM percentage of maximal binding for erythrocyte insulin receptors (2.25 +/- 0.21%), compared with results in 11 clinically normal pet dogs (4.29 +/- 0.42%). The decrease in erythrocyte receptor binding was attributed to significant (P less than 0.01) decrease in high-affinity receptor sites in dogs with hyperadrenocorticism (14.5 +/- 2.8), compared with clinically normal dogs (31.2 +/- 4.3). Significant differences in receptor affinity were not apparent between the 2 groups. Percentage of maximal binding for erythrocyte insulin receptors for dogs with hyperadrenocorticism was inversely correlated with serum insulin concentration (r = -0.85, P less than 0.01). Results indicate that the observed decrease in erythrocyte insulin receptor binding could contribute to insulin resistance and hyperinsulinemia associated with hyperadrenocorticism. Alternatively, decreased binding of insulin receptors in animals with hyperadrenocorticism may result from down-regulation secondary to hyperinsulinemia itself caused by insulin resistance at a postreceptor site (decreased responsiveness).
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PMID:Erythrocyte insulin receptors in dogs with spontaneous hyperadrenocorticism. 188 96

To elucidate the mechanism responsible for the decreased insulin binding to erythrocytes in uremic patients, the effects of incubation with sera obtained from uremic patients or with methylguanidine, respectively, on insulin binding were examined. Insulin binding to erythrocytes from uremic patients was lower than that from normal subjects (3.1 +/- 0.19% vs 6.6 +/- 0.33%, Mean +/- SEM, P less than .005), being due mainly to decreased binding affinity (58% of control). Incubation of erythrocytes with 1:5 diluted sera of uremic patients resulted in decreased insulin binding (65 +/- 5% of control) and this decrease was restored to the level of 78 +/- 3% of the controls after incubation with buffer for 12 h. Methylguanidine inhibited insulin binding to erythrocytes in a dose-dependent manner. Post-dialyzed serum with 100 ng/ml of methylguanidine (as seen in pre-dialyzed uremic patients) inhibited insulin binding to erythrocytes as much as pre-dialyzed serum (54.3 +/- 3% vs 47 +/- 1% of control). Incubation of IM-9 lymphocytes with 100 ng/ml of methylguanidine did not alter the insulin receptor mRNA level. These results suggest that methylguanidine inhibits insulin binding to its receptor, resulting in decreased insulin binding to erythrocytes.
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PMID:Inhibitory effect of methylguanidine on insulin binding to its receptor. Mechanism underlying insulin resistance in uremia. 195 80

The effect of a controlled stress (DPT inoculation) on the hormonal control of glucose homeostasis was investigated in children nutritionally rehabilitated from severe malnutrition. The age range of the 15 children studied was 6-26 months. Plasma insulin (INS), growth hormone (GH) and interleukin-1 (IL-1) were measured by radioimmunoassay; plasma glucose (GLU) by a glucose oxidase method; and red cell insulin binding (%SB) was determined, using A-14 monoiodinated insulin. Measurements were made on two occasions: (T-0) at 10 a.m., 12 hr before DPT inoculation, and (T-36) 36 hr. after inoculation. On both occasions, 4 hr post-prandial blood samples were used, and the mean body temperature (T) on the day of the test was determined. Red cell insulin binding (%SB) was significantly higher at T-36 than at T-0 (16.8 +/- 1.7 vs 12.1 +/- 1.2 (14), p = 0.005). (Results were expressed as mean +/- SEM, numbers of paired observations in parentheses). The higher %SB after DPT was accompanied by an increase in the number of receptor sites (S) (29.05 +/- 6.5 vs 15.6 +/- 2.5 (14), p = 0.025). However, insulin receptor affinity (K x 10(9) M-1) was decreased (0.7 +/- 0.1 vs 1.5 +/- 0.3 (14), p = 0.008). There were no significant differences in the plasma levels of insulin, glucose and interleukin-1, but plasma growth hormone (microU/ml) was increased after DPT, (18.0 +/- 3.0 vs. 11.5 +/- 1.2 (13), p = 0.04). Body temperature (degree C) was also significantly increased after DPT, (99.6 +/- 0.4 vs. 98.3 +/- 0.2 (14), p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of DPT inoculation on the hormonal control of glucose homeostasis in children recovered from malnutrition. 208 66

Insulin-like growth factor I (IGF-I) and insulin have been implicated in the regulation of differentiated functions in many cells. We have reported that IGF-I stimulates the release of decidual PRL, acting through the type I IGF receptor (1). To determine whether insulin regulates the synthesis and secretion of decidual PRL, monolayer cultures of human decidual cells were exposed to insulin at concentrations ranging from 10 ng to 10 micrograms/ml for up to 5 days. Insulin stimulated a dose-dependent increase in PRL release (half-maximal concentration, 50 ng/ml), beginning 48 h after initial exposure. Insulin-exposed cells released 62 +/- 2% (mean +/- SEM), 97 +/- 3% and 82 +/- 6% more PRL than control cultures on days 3, 4, and 5, respectively. Insulin also stimulated de novo PRL synthesis. During the final 24-h culture period, insulin-exposed cells released 73 +/- 7% more immunoprecipitable [35S]-methionyl PRL than control cells, comparable to the 60 +/- 7% increase in PRL (by RIA) during the same period. Insulin effects were relatively specific to PRL, since insulin had a much smaller effect on the synthesis of total trichloroacetic acid-precipitable proteins. Additionally, insulin had no significant effect on cell number, total DNA, or total cellular protein. Specific and saturable insulin-binding sites were observed in decidual cells, and polyclonal antibodies to the insulin receptor acted as insulin agonists, stimulating an increase in PRL release comparable to that produced by insulin alone. These observations suggest that the responses to insulin are mediated through the insulin receptor. Furthermore, our studies suggest that insulin may have a role in the regulation of PRL synthesis and release from human decidua.
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PMID:Insulin stimulates the synthesis and release of prolactin from human decidual cells. 265 48

Crossbred gilts (controls; n = 7) had 8.8 +/- 1.1% (mean +/- SEM) maximum binding of [125I]insulin to insulin receptors on erythrocytes. The number of insulin-binding sites per cell was 137 +/- 19, with a binding affinity ranging from 7.4 X 10(7)M-1 to 11.2 X 10(7)M-1 and mean of 8.8 X 10(7)M-1. Pregnant sows (n = 5) had a significant increase (P less than 0.01) in maximum binding due to an increase in number of receptor sites per cell. Lactating sows fed a high-fiber diet (n = 3) and a low-fiber diet (n = 4) did not develop a significant difference in maximum binding of insulin. Sows fed the low-fiber diet had a significantly higher number of binding sites and a significantly lower binding affinity than did sows fed a high-fiber diet. Receptor-binding affinity was lower in the low-fiber diet group than in cycling gilts, whereas data from sows fed the high-fiber diet did not differ from data for cycling gilts. Data from this study indicated that insulin receptors of swine erythrocytes have binding characteristics similar to those in other species. Pregnancy and diet will alter insulin receptor binding in swine.
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PMID:Binding characteristics of swine erythrocyte insulin receptors. 299 89

To characterize the insulin-like growth factor I (IGF-I) receptor on human erythrocytes, cells were purified from peripheral blood by Ficoll-Hypaque gradient centrifugation and incubated with [125I]IGF-I. Specific binding was maximal at pH 8.0 after 24 h at 4 C and increased linearly with cell number to 3.9 +/- 0.2% (+/- SEM) for 3.0 X 10(9) cells/ml. The Scatchard plot of the binding data was linear, with 7 fmol [125I]IGF-I bound/10(9) cells and an affinity constant (K) of 1.8 X 10(9) M-1. Unlabeled IGF-I inhibited tracer binding half-maximally at 6 ng/ml. Multiplication-stimulating activity (or rat IGF-II) was 40% as potent (ED50, 15 ng/ml), whereas insulin and proinsulin were 30- to 500-fold less potent. A monoclonal antibody to the IGF-I receptor (alpha IR-3) inhibited IGF-I binding by 50% at a 1:1000 dilution and by 80% at a 1:250 dilution. Insulin binding was unaffected by the same dilutions. IGF-I receptor phosphorylation was studied in erythrocyte ghosts prepared by hypotonic lysis and solubilized in 1% Triton. The extract was preincubated with and without 100 ng/ml IGF-I or porcine insulin and incubated with [gamma-32P]ATP in the presence of Mn2+, and the receptor was identified by immunoprecipitation with alpha IR-3 antibody and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. IGF-I stimulated 4-fold the incorporation of 32P into a protein of 95,000 mol wt, which was immunoprecipitated by alpha IR-3; insulin produced a 2-fold stimulation of this protein. This protein corresponds to the beta-subunit of the IGF-I receptor. These data demonstrate that human erythrocytes have specific receptors for IGF-I, and that this IGF-I receptor, like the insulin receptor, undergoes ligand-stimulated autophosphorylation. Thus, analysis of erythrocyte IGF-I binding and receptor phosphorylation may be useful tools for the study of patients with a variety of growth disorders.
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PMID:The human erythrocyte insulin-like growth factor I receptor: characterization and demonstration of ligand-stimulated autophosphorylation. 300 55

Cultured IM-9 lymphocytes were preincubated with 1 microM insulin, a condition resulting in a 56% reduction in cell surface insulin receptors. Cellular proteins were then metabolically labeled, and the radioactivity incorporated into the insulin proreceptor and receptor mature subunits was measured over a 4-hr chase period. As early as 30 min of chase, incorporation into the proreceptor was 28 +/- 6% higher in down-regulated cells than in control cells (mean +/- SEM, P less than 0.05). By 1 hr of chase, the difference reached 41 +/- 14% for the proreceptor and 84 +/- 28% for the alpha subunit (P less than 0.01); values returned to normal by 2 hr. At 4 hr of chase, labeling of the alpha subunit of down-regulated cells was diminished 36 +/- 9% below control (P less than 0.05). The increased biosynthetic rate of the proreceptor was more prominent when the chase medium contained 25 microM monensin, an inhibitor of processing of the proreceptor into mature subunits. Similar effects occurred whether [3H]mannose or [3H]lysine was used as biosynthetic marker. The effect was specific for the insulin receptor. These data demonstrate that insulin receptor homologous down-regulation is associated with increased proreceptor biosynthesis and processing into mature subunits. This might represent a cellular mechanism compensating for insulin-induced receptor loss.
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PMID:Homologous down-regulation of the insulin receptor is associated with increased receptor biosynthesis in cultured human lymphocytes (IM-9 line). 309 91


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