The effect of rosiglitazone on the liver: Decreased gluconeogenesis in patients with type 2 diabetes

Amalia Gastaldelli, Yoshinori Miyazaki, Maura Pettiti, Eleonora Santini, Demetrio Ciociaro, Ralph A. DeFronzo, Ele Ferrannini

Resultado de la investigación: Articlerevisión exhaustiva

59 Citas (Scopus)

Resumen

Aims/Hypothesis: Diabetic hyperglycemia results from insulin resistance of peripheral tissues and glucose overproduction due to increased gluconeogenesis (GNG). Thiazolidinediones have been shown to improve glycemic control and increase peripheral insulin sensitivity. Whether chronic thiazolidinedione treatment is associated with a decrease in GNG has not been determined. Materials and Methods: We studied 26 diet-treated type 2 diabetic patients randomly assigned to rosiglitazone (RSG; 8 mg/d; n = 13) or placebo (n = 13) for 12 wk. At baseline and 12 wk, we measured endogenous glucose production (by [3H]glucose infusion) and GNG(by the [2H]2O technique) after a 15-h fast. Peripheral insulin sensitivity was evaluated by a two-step (240 and 960 pmol/min/m-2) euglycemic insulin clamp. Results: Compared with placebo, RSG reduced fasting plasma glucose (9.7 ± 0.7 to 7.4 ± 0.3 mmol/liter; P < 0.001), fasting fractional GNG (-15 ± 4%; P = 0.002), and fasting GNG flux (-3.9 ± 1.2 μmol/min/kg fat-free mass; P = 0.004), with no effect on glycogenolytic flux. Changes in GNG flux and fasting glucose were tightly correlated (r = 0.83; P < 0.0001). During both clamp steps, RSG enhanced insulin-mediated glucose clearance (by 26% and 31%; P = 0.01 and P < 0.02, respectively). In a subgroup of patients studied with magnetic resonance imaging, the reduction in GNG flux was correlated (r = 0.65; P < 0.02) with the reduction in visceral fat area. Conclusion/Interpretation: RSG increases peripheral tissue insulin sensitivity and decreases endogenous glucose release via an inhibition of gluconeogenesis.

Idioma originalEnglish (US)
Páginas (desde-hasta)806-812
Número de páginas7
PublicaciónJournal of Clinical Endocrinology and Metabolism
Volumen91
N.º3
DOI
EstadoPublished - mar. 2006

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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