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Titolo:
In obese individuals dexfenfluramine corrects molecular derangements reflecting insulin resistance
Autore:
Piccinini, M; Rabbone, I; Novi, RF; Alberto, G; Mostert, M; Musso, A; Vai, S; Gamba, S; Rinaudo, MT;
Indirizzi:
Univ Turin, Dipartimento Med & Oncol Sperimentale, Sez Biochim, I-10126 Turin, Italy Univ Turin Turin Italy I-10126 entale, Sez Biochim, I-10126 Turin, Italy Univ Turin, Dept Internal Med, I-10126 Turin, Italy Univ Turin Turin Italy I-10126 , Dept Internal Med, I-10126 Turin, Italy Univ Turin, Dept Paediat Sci, I-10126 Turin, Italy Univ Turin Turin Italy I-10126 n, Dept Paediat Sci, I-10126 Turin, Italy Maria Vittoria Hosp, Karen Bruni Antidiabet Ctr, I-10100 Turin, Italy Maria Vittoria Hosp Turin Italy I-10100 diabet Ctr, I-10100 Turin, Italy
Titolo Testata:
INTERNATIONAL JOURNAL OF OBESITY
fascicolo: 6, volume: 24, anno: 2000,
pagine: 735 - 741
SICI:
0307-0565(200006)24:6<735:IOIDCM>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
PYRUVATE-DEHYDROGENASE COMPLEX; II DIABETIC SUBJECTS; CIRCULATING LYMPHOCYTES; E1-ALPHA SUBUNIT; GLUCOSE DISPOSAL; PROTEIN-KINASE; NIDDM PATIENTS; D-FENFLURAMINE; BODY-WEIGHT; FAT DIET;
Keywords:
dexfenfluramine; pyruvate dehydrogenase; circulating lymphocytes; insulin sensitivity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Rinaudo, MT Univ Turin, Dipartimento Med & Oncol Sperimentale, Sez Biochim, Via Michelangelo 27-B, I-10126 Turin, Italy Univ Turin Via Michelangelo 27-B Turin Italy I-10126 n, Italy
Citazione:
M. Piccinini et al., "In obese individuals dexfenfluramine corrects molecular derangements reflecting insulin resistance", INT J OBES, 24(6), 2000, pp. 735-741

Abstract

BACKGROUND: Circulating lymphocytes of obese individuals with and without type 2 diabetes have derangements of pyruvate dehydrogenase (PDH) that are described as reflecting a disorder underlying systemic insulin resistance, namely basal activity below normal and, in vitro, unresponsiveness to insulin at 33 pmol/l and activation at 330 pmol/l instead of activation and inhibition as in controls. OBJECTIVE: To explore whether the above enzyme derangements are overcome in obese individuals on dexfenfluramine treatment, known to improve poor peripheral insulin sensitivity. METHODS: Fifteen obese diabetic patients and 15 age-matched euglycaemic obese subjects with normal glucose tolerance were enrolled for a trial composed of two 21-day periods; in the first (D-(21)-D-0), participants received a placebo, and in the second (D-0- D-21), dexfenfluramine (30 mg/day). At D-(21), D-0 and D-21 participants were evaluated for weight, BMI, fasting glycaemia (FG), fasting insulinaemia (FI), fasting insulin resistance index (FIRI), area under the glycaemic (G-AUC) and insulinaemic (I-AUC) curves from an OGT test, and for PDH activity assayed in their circulating lymphocytes before (basal activity) and after incubation with 33 or 330 pmol/l insulin. At D-2, basal PDH activity and clinical parameters were assayed. RESULTS: In both groups of participants at D-0 all parameters tested were constant with respect to D-21; at D-2, only basal PDH activity rose significantly; at D-21, basal and insulin stimulated PDH activities were normalized and weight decreased significantly, as did FG, Fl, FIRI and G-AUC in the diabetic, and FI, FIRI, G-AUC and I-AUC in the non-diabetic participants. CONCLUSION: In obese, non-diabetic and diabetic individuals on dexfenfluramine treatment, amelioration of clinical parameters and indexes of poor insulin sensitivity of blood glucose homeostasis are preceded by correction, in their circulating lymphocytes, of PDH derangements described as reflecting a disorder underlying insulin resistance.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 12:10:14