Improvement with metformin in insulin internalization and processing in monocytes from NIDDM patients(86 visite) Benzi L, Trischitta V, Ciccarone A, Cecchetti P, Brunetti A, Squatrito S, Marchetti P, Vigneri R, Navalesi R
Parole chiave: Metformin, Radioisotope, Article, Controlled Study, Drug Effect, Glucose Blood Level, High Performance Liquid Chromatography, Human, Human Cell, Hyperinsulinemia, In Vitro Study, Insulin Binding, Insulin Blood Level, Insulin Degradation, Non Insulin Dependent Diabetes Mellitus, Obesity, Priority Journal, Biological Transport, Blood Glucose, Non-Insulin-Dependent, Kinetics, Middle Age, Monocytes, Obesity In Diabetes, Reference Values, Support, Non-U.S. Gov, Non-U. S. Gov,
Cattedra di Malatti, del Ricambio, Inst. di Clinica Medica II, Via Roma 67, 56100 Pisa, Italy
This study investigated the relative effect of obesity alone and in combination with non-insulin-dependent diabetes mellitus (NIDDM) on the intracellular processing of insulin and evaluated the effect of metformin therapy on this process. Monocytes from 11 obese hyperinsulinemic subjects, 13 obese hyperinsulinemic NIDDM patients, and 7 nondiabetic control subjects were incubated with A14-125I-labeled insulin for 60 min at 37°C, and intracellular insulin degradation was characterized by high-performance liquid chromatography. total cell-associated insulin (insulin binding) and internalized and degraded insulin were decreased in obese subjects and significantly decreased in obese NIDDM patients compared with nondiabetic control subjects. In NIDDM patients, intracellular insulin degradation was inversely correlated with fasting plasma glucose (P < 0.01). Eight obese subjects and 9 obese NIDDM patients were restudied after 4 wk of therapy with metformin (850 mg twice a day). Plasma levels of the drug were superimposable in the two groups. Metformin therapy did not change glucose and insulin levels in obese subjects but caused a decrease in blood glucose in obese NIDDM patients. Total cell-associated radioactivity (insulin binding) significantly increased in both groups (P < 0.01). On the contrary, internalized radioactivity increased (0.83 ± 0.3 vs. 1.31 ± 0.35%, P < 0.01), and similarly, insulin degradation was enhanced (54.6 ± 8.9 vs. 74.22 ± 9.15%, P < 0.01) only in monocytes from obese NIDDM patients. However, the levels of these parameters were still lower than in control subjects (internalization, 2.94 ± 0.68%; degradation, 93.03 ± 3.7%). Plasma metformin concentrations showed a significant correlation with total cell-associated radioactivity in obese subjects (P < 0.01) and obese NIDDM patients (P < 0.05). Moreover, in obese NIDDM patients, a significant correlation (P < 0.01) was found between the decrease in fasting plasma glucose and the increase in A14-125I-insulin degradation by monocytes. These data suggest that 1) NIDDM significantly worsens the abnormality of intracellular insulin processing present in obesity; 2) metformin therapy could increase total cell-associated radioactivity, probably with a concentration-dependent effect, independently from its clinical effectiveness; 3) metformin therapy enhances intracellular insulin processing only in cells from obese NIDDM patients, suggesting that the underlying abnormalities may actually be different in these two groups of patients; and 4) the correlation observed in NIDDM patients between the improvement in intracellular insulin degradation and the decrease of plasma glucose levels raises the possibility that metformin-induced degradation changes have a role in insulin action.
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(55 visite) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 DettagliEsporta in BibTeXEsporta in EndNote
Kim YH, Shin SW, Pellicano R, Fagoonee S, Choi IJ, Kim YI, Park B, Choi JM, Kim SG, Choi J, Park JY, Oh S, Yang HJ, Lim JH, Im JP, Kim JS, Jung HC, Ponzetto A, Figura N, Malfertheiner P, Choi IJ, Kook MC, Kim YI, Cho SJ, Lee JY, Kim CG, Park B, Nam BH, Bae SE, Choi KD, Choe J, Kim SO, Na HK, Choi JY, Ahn JY, Jung KW, Lee J, Kim DH, Chang HS, Song HJ, Lee GH, Jung HY, Seta T, Takahashi Y, Noguchi Y, Shikata S, Sakai T, Sakai K, Yamashita Y, Nakayama T, Leja M, Park JY, Murillo R, Liepniece-karele I, Isajevs S, Kikuste I, Rudzite D, Krike P, Parshutin S, Polaka I, Kirsners A, Santare D, Folkmanis V, Daugule I, Plummer M, Herrero R, Tsukamoto T, Nakagawa M, Kiriyama Y, Toyoda T, Cao X, Corral JE, Mera R, Dye CW, Morgan DR, Lee YC, Lin JT, Garcia Martin R, Matia Cubillo A, Lee SH, Park JM, Han YM, Ko WJ, Hahm KB, Leontiadis GI, Ford AC, Ichinose M, Sugano K, Jeong M, Park JM, Han YM, Park KY, Lee DH, Yoo JH, Cho JY, Hahm KB, Bang CS, Baik GH, Shin IS, Kim JB, Suk KT, Yoon JH, Kim YS, Kim DJ * Helicobacter pylori Eradication for Prevention of Metachronous Recurrence after Endoscopic Resection of Early Gastric Cancer(34 visite) N Engl J Med (ISSN: 0028-4793, 0028-4793linking, 1533-4406electronic), 2015 Jun; 30642104201566393291: 749-756. Impact Factor:59.558 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(161 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(308 visite) Rivista Di Neuroradiologia (ISSN: 1120-9976), 2004; 17(6): 807-812. Impact Factor:0.023 DettagliEsporta in BibTeXEsporta in EndNote