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Titolo:
Mechanisms of action of thiazolidinediones
Autore:
Girard, J;
Indirizzi:
CNRS, UPR 1524, Ctr Rech Endocrinol Mol & Dev, F-92190 Meudon, France CNRS Meudon France F-92190 Endocrinol Mol & Dev, F-92190 Meudon, France
Titolo Testata:
DIABETES & METABOLISM
fascicolo: 2, volume: 27, anno: 2001,
parte:, 2
pagine: 271 - 278
SICI:
1262-3636(200104)27:2<271:MOAOT>2.0.ZU;2-B
Fonte:
ISI
Lingua:
FRE
Soggetto:
ACTIVATED RECEPTOR-GAMMA; RAT SKELETAL-MUSCLE; STIMULATED GLUCOSE-TRANSPORT; IMPROVED INSULIN-SENSITIVITY; OBESE PREDIABETIC RATS; DIABETIC FATTY RATS; BETA-CELL FUNCTION; ZUCKER FA/FA RAT; PROTEIN-KINASE-B; PPAR-GAMMA;
Keywords:
thiazolidinediones; insulin resistance; glucose utilization; adipocyte; PPAR; skeletal muscle; TNF alpha; glucose-fatty acid cycle;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
69
Recensione:
Indirizzi per estratti:
Indirizzo: Girard, J CNRS, UPR 1524, Ctr Rech Endocrinol Mol & Dev, 9 Rue Jules Hetzel, F-92190Meudon, France CNRS 9 Rue Jules Hetzel Meudon France F-92190 190Meudon, France
Citazione:
J. Girard, "Mechanisms of action of thiazolidinediones", DIABETE MET, 27(2), 2001, pp. 271-278

Abstract

The recent discovery and marketing of a new class of antidiabetic drug improving insulin sensitivity, the thiazolidinediones (TZD), has opened interesting therapeutic perspectives. Those molecules correct hyperglycemia and hyperinsulinemia in several animal models of NDDM. Clinical studies in humanhave confirmed that TZD lowered postprandial and postabsorptive glycemia and insulinemia. Glucose clamp studies have clearly shown an improvement of insulin-induced glucose utilization (in skeletal muscle). In contrast, the inhibition of glucose production in response to insulin was much less reproducible. TZD have also been used with success to treat insulin resistance in nondiabetic obeses, in glucose-intolerant prediabetic subjects and in patients with polycystic ovary syndrom (pcos). Nevertheless, TZD appears less efficient in human than in animal models. TZD bind to an isoform of a nuclear receptor, the PPAR gamma (Peroxisome Proliferator Activated Receptor). PPAR gamma is a transcription factor which, after heterodimerization with the retinoid receptor (RXR), bind to specific response elements of a number of target genes and control their transcription. There is an excellent correlation between the hypoglycemic effects of TZD in vivo and their affinity for PPAR gamma in vitro, but the site of action and the molecular mechanism of TZD still remain poorly known. In human, skeletal muscles are responsible for more than 80% of glucose uptake in response to insulin. Unfortunately, skeletal muscles contain limited amounts of PPAR gamma. How TZD with the principal site of action being adipose tissue, can improve glucose metabolism in skeletal muscle ? One possibility is the following: 1- TZD stimulate adipocyte differentiation, generating small adipocytes more sensitive to insulin, 2-TZD decrease TNF alpha and fattyacids production by adipocytes and indirectly improve insulin-resistance in skeletal muscles (improvement of insulin signaling, inhibition of glucose-fatty acid cycle). Another possibility is that chronic treatment with TZD induces PPAR gamma expression in skeletal muscles. Finally, TZD could have a direct effect on skeletal muscles, independently of PPAR gamma.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/04/20 alle ore 22:48:09