Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:034761 (insulin)
 211,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NSILA-s (nonsuppressible insulin-like activity, soluble in acid ethanol) is a serum peptide that has insulin-like and growth-promoting activities. We have demonstrated previously that liver plasma membranes possess separate receptors for NSILA-s and insulin and have characterized the insulin receptor in detail. In the present study we have characterized the properties and specificity of the NSILA-s receptor and compared them to those of the insulin receptor in the same tissue. Both 125I-NSILA-s and 125I-insulin bind rapidly and reversibly to their receptors in liver membranes; maximal NSILA-s binding occurs at 20 degrees while maximal insulin binding is seen at 1-4 degrees. The pH optimum for NSILA-s binding is broad (6.0 to 8.0), in contrast to the very sharp pH optimum (7.5 to 8.0) for insulin binding. Both receptors exhibit a high degree of specificity. With the insulin receptor, NSILA-s and insulin analogues compete for binding in proportion to their insulin-like potency: insulin greater than proinsulin greater than NSILA-s. With the NSILA-s receptor, NSILA-s is most potent and the order is reversed: NSILA-s greater than proinsulin greater than insulin. Furthermore, six preparations of NSILA-s which varied 70-fold in biological activity competed for 125I-NSILA-s binding in order of their potencies. NSILA-s which had been inactivated biologically by reduction and aminoethylation and growth hormone were less than 1/100,000 as potent as the most purified NSILA-s preparation. Purified preparations of fibroblast growth factor, epidermal growth factor, nerve growth factor, and somatomedins B and C were less than 1% as effective as NSILA-s in competing for the 125I-NSILA-s suggesting that these factors act through other receptors. In contrast, somatomedin A was 10% as active as NSILA-s and multiplication-stimulating activity was fully as active as NSILA-s in competing for the NSILA-s receptor. Analysis of the data suggests that there are approximately 50 times more insulin receptors than NSILA-s receptors per liver cell, while the apparent affinity of NSILA-s receptors is somewhat higher than that of the insulin receptor.
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PMID:The NSILA-s receptor in liver plasma membranes. Characterization and comparison with the insulin receptor. 0 Mar 91

The fluorescnece porperties of 1,8-TNS in relation to the polarity and viscosity of the solvents have been studied and found to be just as useful as those of its positional isomer 2,6-TNS in the capacity of being a fluorescent probe. The properties of the hydrophobic region of insulin, des-pentapeptide (B26-30)- insulin (DPI), bovine plasma albumin, lysozyme, and ovalbumin have been investigated by employing this fluorescent probe. It has been shown that there is a small but definite hydrophobic region in DPI just as in insulin. This suggests that removal of the C-terminal pentapeptide does not impair seriously the hydrophobic structure related to the binding with insulin receptor. However, at physiologic pH, the hydrophobic region of DPI becomes more exposed than that of insulin and its conformation is less stable. As the pH is increased, the local conformation of the DPI molecule probably suffers some distortion, which damages the conformation of the hydrophobic region to a certain extent. In comparison with insulin, the DPI molecule is relatively loose and unstable.
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PMID:Structural studies on des-pentapeptide (B26-30)-insulin. IV. A preliminary investigation on the hydrophobic region by employing a fluorescence probe, 1-p-toluidinylnaphthalene-8-sulphonate. 1 Jun 23

Avian erythrocytes possess insulin receptors which have binding properties that are virtually identical to those of the well studied mammalian insulin receptors. The affinity for porcine insulin was identical for the turkey and mammalian receptors over the entire range of insulin concentrations, as was the affinity of each of four insulin analogues which differed 300-fold in biological potency. Insulin induced acceleration of dissociation (i.e., the negatively cooperativite site-site interaction) was indistinguishable over a 10(6) range of insulin concentrations. Sharp pH dependence of binding was identical for turkey and mammalian receptors. The effects of temperature on association, dissociation and steady state binding were also identical. Thus, although birds and mammals have evolved separately for 300 million years there has been little change in the properties of the insulin receptor over this time period.
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PMID:The insulin receptor of the turkey erythrocyte: similarity to mammalian insulin receptors. 1 89

Turkey erythrocytes possess insulin receptors with binding properties very similar to those of mammalian insulin receptors. In the present study, the insulin receptor of the avian erythrocyte has been solubilized in Triton X-100, extensively characterized and partially purified, and its properties compared to those of the membrane-bound receptor. The solubilized insulin receptor has a Stokes radius of 70 A and an apparent molecular weight of 300 000 in 0.05% Triton. The binding of insulin to the soluble receptor was very similar to the binding observed with the membrane-bound receptor. Thus, binding was markedly temperature dependent for both the soluble and membrane-bound forms, although the kinetics of binding were slower with the soluble receptor. Both forms of the receptor also showed a sharp pH optimum; however, solubilization produced a shift from maximal binding at pH 7.8 to pH 7.3. The soluble receptor also retained insulin analog specificity, ion sensitivity and negative cooperativity. The soluble receptor did not appear to degrade either bound or free insulin. On DEAE-cellulose chromatography the receptor eluted as a single peak. The specific activity of this partially purified preparation was 25--30 pmol/mg protein (about 500-fold enrichment over crude extract and 5-fold over highly purified membranes). Extensive attempts to purify further the receptor by gel filtration, carboxymethyl-cellulose chromatography and affinity chromatography resulted in either a very low yield or only modest enrichment. Purification was also complicated because the receptor was easily denatured; about 40% of the activity was lost after a 90-min exposure to 3 M urea or pH 4.5. These data suggest that the insulin receptor retains its properties in the absence of the lipid bilayer of the membrane. Complete purification will be difficult due to a lack of stability under a number of conditions.
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PMID:Properties and partial purification of the detergent-solubilized insulin receptor: a demonstration of negative cooperativity in micellar solution. 2 36

The insulin receptor for human placental membranes has been solubilized in Triton X-100 and its properties have been examined in detail. Binding of [125 I]iodoinsulin to the soluble receptor is markedly inhibited by increas-ng concentrations of Triton X-100, due to a fall in receptor affinity. In 0.02--0.10% Triton X-100, the soluble receptor exhibits all the essential characteristics of the intact or particulate receptor. These include strict specificity for insulin and its analogues, increase in steady state binding with decrease in temperature, a pH optimum at 7.8--8.0, and negatively cooperative site-site interactions. The initial association rate of [125 I]iodoinsulin and the soluble receptor is a direct function of temperature, but the level of steady-state binding is lower at higher temperatures due to a marked increase in dissociation rate. Scatchard binding plots are curvilinear and show a large increase in affinity at 4 C with no change in total binding capacity (R0); increased binding to the particulate placental membrane at 4 C is due chiefly to an increase in R3. Negative cooperatively in the soluble receptor has been confirmed by kinetic experiments; thus, the dissociation of [125I]iodoinsulin from the receptor in the presence of "infinite" dilution is accelerated in the presence of 10(-8) M unlabeled insulin. The apparent molecular weight of the placental receptor, determined by gel filtration on 6% agarose, is approximately 300,000. These studies show that the basic properties of the insulin receptor do not depend on it being an integral conponent of the cell membrane.
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PMID:The effect of solubilization on the properties of the insulin receptor of human placental membranes. 3 98

A sensitive and specific radioimmunoassay for the insulin receptor has been developed employing receptor autoantibodies from the serum of a patient with insulin-resistant diabetes. The assay detects insulin binding sites at concentrations as low as 0.1 nanomolar; distinguishes between receptors originating from human placental membranes, human lymphoblastoid cells, and mouse liver membranes; and measures the receptor independently of its binding function. Down-regulation, or loss of binding after exposure to insulin, is associated with loss of immunoreactive receptor.
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PMID:Radioimmunoassay of the insulin receptor: a new probe of receptor structure and function. 8 75

Human insulin receptors obtained from normal human placentae were highly purified by affinity chromatography and used to immunize rabbits. The immunological response was evaluated in order to reveal the presence of antibodies blocking the binding of insulin to monocytes of normal subjects. Since no blocking activity was found IgG from rabbits were coupled to agarose in order to evaluate the presence of antibodies directed to determinant(s) other than the insulin binding site. One rabbit was found to produce antibodies binding the insulin receptor on a site different from the insulin binding site.
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PMID:Specificities of rabbit anti-human insulin receptor antibodies. 9 85

The role of the surrounding membrane structure on the binding characteristics of the insulin receptor was studied by using several digestive enzymes. The effects observed with particulate membrane preparations are compared with those from soluble receptor preparations. beta-Galactosidase and neuraminidase had no effect on insulin binding to either particulate or soluble receptors from human placentae. Exposure to 2 units of phospholipase C/ml increased insulin binding to particulate membranes, but was without effect on the soluble receptor preparation. The increase in binding to particulate membranes was shown to be due to an increase in apparent receptor number. After 5 min exposure to 500 microgram of trypsin/ml there was an increase in insulin binding to the particulate membrane fraction, owing to an increase in receptor affinity. After 15 min exposure to this amount of trypsin, binding decreased, owing to a progressive decrease in receptor availability. In contrast, this concentration of trypsin had no effect on the solubilized receptor preparation. Because of the differential effects of phospholipase C and trypsin on the particulate compared with the solubilized receptor preparations, it is concluded that the effects of these enzymes were due to an effect on the surrounding membrane structure. Changes in receptor configuration due to alterations within the adjoining membrane provide a potential mechanism for mediating short-term alterations in receptor function.
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PMID:The effects of digestive enzymes on characteristics of placental insulin receptor. Comparison of particulate and soluble receptor preparations. 10 Jan 6

Insulin sensitivity with respect to changes in blood glucose, lactate, and ketone body concentrations has been studied in normal and streptozotocin-diabetic rats. Insulin was infused at doses ranging from 0.03 to 100 U/kg/hr and dose response curves established. Maximal responsiveness was achieved at 1 U/kg/hr for glucose and 0.3 U/kg/hr for ketone bodies in normal rats. In diabetic rats, responsiveness and sensitivity were directly proportional to pH. When pH was less than 6.9, there was little or no response. Ammonium chloride administration to normal rats or to mildly acidotic diabetic rats caused almost total loss of responsiveness to insulin. The insulin insensitivity found in severely acidemic diabetic rats could be reversed by sodium bicarbonate administration. Liver and muscle metabolite patterns suggested that loss of responsiveness and sensitivity was due both to effects at the insulin receptor and direct effects on glycolysis, presumptively at phosphofructokinase. Reversal of these changes with bicarbonate was associated with a fall in hepatic ATP content. It is suggested that the insulin resistance of severe diabetic ketoacidosis in the rat is secondary to inhibitory effects of hydrogen ion; the exact mechanism remains to be established.
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PMID:Acidemia and insulin resistance in the diabetic ketoacidotic rat. 10 3

Autoantibodies to the insulin receptor mimic the effects of insulin on glycogen synthase and phosphorylase. The interaction of antibodies with adipocyte cell surface insulin receptors seems sufficient to promote stable changes in the activities of these intracellular enzymes, suggesting that internalization or processing of insulin is not important in the generation of these biological responses.
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PMID:Autoantibodies to the insulin receptor activate glycogen synthase in rat adipocytes. 10 36


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