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  • 1
    ISSN: 1432-0428
    Keywords: Insulin receptor ; insulin proreceptor ; insulin resistance ; transformed lymphocytes ; point mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An alteration of an amino acid sequence in the processing site of the insulin proreceptor by a point mutation of the insulin receptor gene produced extreme insulin resistance. We characterized functional properties of the unprocessed insulin receptor in transformed lymphocytes from a patient. Insulin binding to intact cells and to a partially purified insulin receptor preparation was radically decreased to 20% and 18% of the control values, respectively. In competitive insulin binding to intact cells, [LeuA3]-, [LeuB24]-, [SerB24-insulin, and mini-proinsulin ([B(1–29)-Ala-Ala-Lys-A(1–21)]-insulin) had the same relative binding activity in both the patient's and the control cells, but proinsulin and IGF-I were markedly less able to displace 125I-insulin in the patient's cells. In contrast to the study in intact cells, proinsulin and IGF-I as well as other insulin analogues had the same relative binding activity to bind to the partially lectin-purified insulin receptor preparations from both the patient's and the control cells. As regards the signal transduction after receptor binding, insulin-stimulated autophosphorylation of the unprocessed insulin proreceptor occurred proportionally to the amount of decreased insulin binding. With 0.025% trypsin treatment, the abnormal binding characteristics and autophosphorylation were normalized through conversion to functionally normal receptors. In spite of the abnormal processing, self-association of receptors into oligomeric structures was observed in the proreceptor. These results suggest that the unprocessed insulin proreceptor in the plasma membranes has an altered conformation which affects its binding characteristics but not its intramolecular signal transmission.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2013
    Keywords: Tetrodotoxin ; Kurzschlußstrom ; Harnblase einer Kröte ; Verbrauch des Sauerstoffs ; aktiver Natriumtransport ; Tetrodotoxin ; Short-circuit Current ; Toad Bladder ; Oxygen Consumption ; Active Transport of Sodium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary 1. Tetrodotoxin (TTX) inhibited active sodium transport of the urinary bladder of toad,Bufo bufo japonicus, at the concentration of 3.6×10−4 m. TTX was effective when it was added in the serosal chamber, but ineffective in the mucosal chamber. 2. TTX did not inhibit the Na, K-dependent ATPase activity of the homogenate of the bladder. 3. TTX suppressed the oxygen consumption of the toad bladder membrane in both sodium containing and sodium-free medium at the concentration of 3.6×10−4 m. TTX slightly suppressed the state IV of the rat liver mitochondrial respiration at the concentration of 1.4×10−4 m. 4. These results suggest that TTX inhibits the active sodium transport of the toad bladder by suppressing the electron transport system of mitochondria
    Notes: Zusammenfassung 1. Wir untersuchten die Wirkungen von Tetrodotoxin (TTX) auf den aktiven Natriumtransport für die biologische Membran, wobei wir die Harnblase einer Kröte,Bufo bufo japonicus, benutzten. TTX hemmte die Wirkungen in der Konzentration von 3,6 · 10−4 m. Dabei zeigt TTX eine prompte und schnelle reversible Verminderung von Kurzschlußstrom und Potentialdifferenz mit der Zugabe auf der Innenseite der Membran, während es im Fall der Außenseite unwirksam blieb. 2. TTX hatte keine Hemmung auf die Na- und K-abhängende ATPase Aktivität des Homogenitats der Harnblase der Kröte. 3. TTX unterdrückte den Verbrauch des Sauerstoffs für die Membran der Harnblase der Kröte sowohl im natriumenthaltenden als auch im natriumfreien Medium in der Konzentration von 3,6 · 10−4 m. PARABei einer Dosis von 1.4 · 10−4 m wurde eine leichte Hemmung der Mitochondrienatmung der Rattenleber festgestellt. 4. Es läßt sich vermuten, daß TTX durch Unterdrückung des Elektronentransportsystems der Mitochondrien den aktiven Natriumtransport der Harnblase der Kröte hemmt.
    Type of Medium: Electronic Resource
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