Parole chiave: Insulin, Insulin A 14 I 125, Iodine 125, Radioisotope, Tyrosine I 125, Unclassified Drug, Adult, Blood And Hemopoietic System, Cytology, Diabetes Mellitus, Drug Analysis, Drug Binding, Drug Determination, Drug Distribution, Drug Identification, Drug Metabolism, Drug Receptor Binding, Drug Tissue Level, Endocrine System, Etiology, High Performance Liquid Chromatography, Histology, Human, Human Cell, Insulin Resistance, Monocyte, Non Insulin Dependent Diabetes Mellitus, Normal Value, Pharmacokinetics, Priority Journal, Aged, High Pressure Liquid, Type 2, Female, Immunosorbent Techniques, Iodides, Iodine Radioisotopes, Middle Aged,
Cattedra di Endocrinologia e Patologia Costituzionale, Universita di Catania, 95123 Catania, Italy
We studied total cell-associated A14-[125I]insulin radioactivity (including surface-bound and internalized radioactivity), insulin internalization, and its intracellular degradation at 37 C in monocytes from nonobese type II untreated diabetic patients (n = 9) and normal subjects (n = 7). Total cell-associated radioactivity was decreased in diabetic patients [2.65 ± 1.21% (±SD) vs. 4.47 ± 1.04% of total radioactivity; P < 0.01]. Insulin internalization was also reduced in diabetic patients (34.0 ± 6.8% vs. 59.0 ± 11.3% of cell-associated radioactivity; P < 0.01). Using high-performance liquid chromatography six intracellular forms of radioactivity derived from A14-[125I]insulin were identified; 10-20% of intracellular radioactivity had approximately 300,000 mol wt and was identified as radioactivity bound to the insulin receptor, and the remaining intracellular radioactivity included intact A14-[125I]insulin, [125I]iodide, or [125I]tyrosine, and three intermediate compounds. A progressive reduction of intact insulin and a corresponding increase in iodine were found when the incubation time was prolonged. Intracellular insulin degradation was reduced in monocytes from diabetic patients; intracellular intact insulin was 65.6 ± 18.1% vs. 37.4 ± 18.0% of intracellular radioactivity (P < 0.01) after 2 min and 23.6 ± 22.3% vs. 3.9 ± 2.3% (P < 0.01) after 60 min in diabetic patients vs. normal subjects, respectively. In conclusion, 1) human monocytes internalize and degrade insulin in the intracellular compartment in a stepwise time-dependent manner; and 2) in monocytes from type II diabetic patients total cell-associated radioactivity, insulin internalization, and insulin degradation are significantly reduced. These defects may be related to the cellular insulin resistance present in these 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(78 visite) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 DettagliEsporta in BibTeXEsporta in EndNote
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Testino G, Leone S, Fagoonee S, Del Bas JM, Rodriguez B, Puiggros F, Marine S, Rodriguez MA, Morina D, Armengol L, Caimari A, Arola L, Cimini FA, Barchetta I, Carotti S, Bertoccini L, Baroni MG, Vespasiani-gentilucci U, Cavallo MG, Morini S, Nelson JE, Roth CL, Wilson LA, Yates KP, Aouizerat B, Morgan-stevenson V, Whalen E, Hoofnagle A, Mason M, Gersuk V, Yeh MM, Kowdley KV, Lee SM, Jun DW, Cho YK, Jang KS, Kucukazman M, Ata N, Dal K, Yeniova AO, Kefeli A, Basyigit S, Aktas B, Akin KO, Agladioglu K, Ure OS, Topal F, Nazligul Y, Beyan E, Ertugrul DT, Catena C, Cosma C, Camozzi V, Plebani M, Ermani M, Sechi LA, Fallo F, Goto Y, Ray MB, Mendenhall CL, French SW, Gartside PS Serum vitamin A deficiency and increased intrahepatic expression of cytokeratin antigen in alcoholic liver disease(33 visite) Hepatology (ISSN: 1827-1669electronic, 0026-4806linking), 1988 Sep; 83120693611123109(5): 1019-1026. Impact Factor:0.913 DettagliEsporta in BibTeXEsporta in EndNote
675 Records (648 escludendo Abstract e Conferenze). Impact factor totale: 2545.938 (2444.616 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 2687.177 (2582.168 escludendo Abstract e Conferenze).