Defects in insulin-receptor internalization and processing in monocytes of obese subjects and obese NIDDM patients(99 visite) Trischitta V, Brunetti A, Chiavetta A, Benzi L, Papa V, Vigneri R
Parole chiave: Insulin, Insulin Receptor, Radioisotope, Adult, Article, Cell Surface, Clinical Article, Controlled Study, Human, Human Cell, Insulin Binding, Insulin Resistance, Monocyte, Non Insulin Dependent Diabetes Mellitus, Obesity, Priority Journal, Radioimmunoassay, Non-Insulin-Dependent, Female, Kinetics, Middle Age, Obesity In Diabetes, Protein Processing, Post-Translational, Reference Values,
Affiliazioni:
Department of Endocrinology, University of Catania, Catania, Italy
Riferimenti:
Non disponibile.
We investigated intracellular processing of the insulin-receptor complex in monocytes from 12 healthy control subjects, 11 obese nondiabetic subjects, and 13 obese patients with non-insulin-dependent diabetes mellitus (NIDDM) by measuring receptor internalization, recovery of cell-surface insulin binding after receptor internalization, and the release of intracellular intact insulin (insulin retroendocytosis). When monocytes from the three groups of subjects were exposed to 100 nM unlabeled insulin for 30 min at 37°C, the subsequent cell-surface 125I-labeled insulin binding was reduced, but the total number of insulin receptors, measured by radioimmunoassay, was not changed. These findings indicate a redistribution of insulin receptors from the surface to the cell interior. Insulin-receptor internalization was significantly lower in monocytes of obese NIDDM patients (mean ± SE 17.8 ± 4.7%) than in obese subjects and healthy control subjects (33.5 ± 4.5%, P < .05, and 34.4 ± 3.7%, P < .02, respectively). Moreover, in downregulated cells, a complete recovery of the initial insulin binding was observed in control subjects but not in obese NIDDM patients or obese nondiabetic subjects. The release of internalized insulin was also reduced in obese NIDDM patients and obese subjects (t( 1/2 ) = 49.0 ± 2.4 min, P < .02; 47.4 ± 5.7 min, P < .05; and 32.9 ± 3.8 in NIDDM patients, obese subjects, and control subjects, respectively). In the radioactivity released from monocytes of obese subjects and obese NIDDM patients, the percentage of intact insulin was higher (P < .05) than in control subjects, suggesting reduced intracellular insulin degradation in obese subjects and obese NIDDM patients. This study indicates that insulin-resistant obese subjects and obese NIDDM patients have multiple postbinding defects of the insulin-receptor intracellular processing. Among these defects, decreased insulin-receptor internalization is specifically associated with diabetic patients.
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(60 visite) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 DettagliEsporta in BibTeXEsporta in EndNote
Santulli G, Cipolletta E, Sorriento D, Del Giudice C, Anastasio A, Monaco S, Maione AS, Condorelli G, Puca A, Trimarco B, Illario M, Iaccarino G * CaMK4 gene deletion induces hypertension(135 visite) J Am Heart Assoc Journal Of The American Heart Association (ISSN: 2047-9980), 2012; 1(4): N/D-N/D. Impact Factor:2.882 DettagliEsporta in BibTeXEsporta in EndNote
Bruni AC, Bernardi L, Colao R, Rubino E, Smirne N, Frangipane F, Terni B, Curcio SA, Mirabelli M, Clodomiro A, Di Lorenzo R, Maletta R, Anfossi M, Gallo M, Geracitano S, Tomaino C, Muraca MG, Leotta A, Lio SG, Pinessi L, Rainero I, Sorbi S, Nee L, Milan G, Pappata S, Postiglione A, Abbamondi N, Forloni G, St George Hyslop P, Rogaeva E, Bugiani O, Giaccone G, Foncin JF, Spillantini MG, Puccio G * Worldwide distribution of PSEN1 Met146Leu mutation: A large variability for a founder mutation(136 visite) Neurology (ISSN: 0028-3878, 1526-632x, 1526-632xelectronic), 2010 Mar 9; 74(10): 798-806. Impact Factor:8.017 DettagliEsporta in BibTeXEsporta in EndNote
Aloj L, Aurilio M, Rinaldi V, D'Ambrosio L, Tesauro D, Peitl PK, Maina T, Mansi R, Von Guggenberg E, Joosten L, Sosabowski JK, Breeman WA, De Blois E, Koelewijn S, Melis M, Waser B, Beetschen K, Reubi JC, De Jong M * The EEE project(177 visite) Proc Int Cosm Ray Conf Icrc Universidad Nacional Autonoma De Mexico, 2007; 5(HEPART2): 977-980. Impact Factor:0 DettagliEsporta in BibTeXEsporta in EndNote
Hesse B, Tagil K, Cuocolo A, Anagnostopoulos C, Bardies M, Bax J, Bengel F, Busemann Sokole E, Davies G, Dondi M, Edenbrandt L, Franken P, Kjaer A, Knuuti J, Lassmann M, Ljungberg M, Marcassa C, Marie PY, Mckiddie F, O'connor M, Prvuolovich E, Underwood R * 3. 0 T perfusion MR imaging(312 visite) Rivista Di Neuroradiologia (ISSN: 1120-9976), 2004; 17(6): 807-812. Impact Factor:0.023 DettagliEsporta in BibTeXEsporta in EndNote
Vitiello M, Finamore E, Falanga A, Raieta K, Cantisani M, Galdiero F, Pedone C, Galdiero M, Galdiero S * Fusion in Coq(144 visite) Lecture Notes In Computer Science (ISSN: 0302-9743, 0302-974335404636319783540463634, 0302-974335402975459783540297543), 2001; 2178LNCS: 583-596. Impact Factor:0.415 DettagliEsporta in BibTeXEsporta in EndNote
