Istituto di Fisiologia Clinica     
Gastaldelli A., Miyazaki Y., Mahankali A., Berria R., Pettiti M., Buzzigoli E., Ferrannini E., Defronzo R. A. The effect of pioglitazone on the liver: role of adiponectin. In: Diabetes Care, vol. 29 pp. 2275 - 2281. American Diabetes Association, 2006.
OBJECTIVE—Diabetic hyperglycemia results from insulin resistance of peripheral tissues and glucose overproduction due to increased gluconeogenesis (GNG). Thiazolidinediones (TZDs) improve peripheral insulin sensitivity, but the effect on the liver is less clear. The goal of this study was to examine the effect of TZDs on GNG. RESEARCH DESIGN AND METHODS—Twenty sulfonylurea-treated type 2 diabetic subjects were randomly assigned (double-blind study) to receive pioglitazone (PIO group; 45 mg/day) or placebo (Plc group) for 4 months to assess endogenous glucose production (EGP) (3-3H-glucose infusion), GNG (D2O technique), and insulin sensitivity by two-step hyperinsulinemic-euglycemic clamp (240 and 960 pmol/min per m2). RESULTS—Fasting plasma glucose (FPG) (10.0 ± 0.8 to 7.7 ± 0.7 mmol/l) and HbA1c (9.0 ± 0.4 to 7.3 ± 0.6%) decreased in the PIO and increased in Plc group (P < 0.05 PIO vs. Plc). Insulin sensitivity increased 40% during high insulin clamp after pioglitazone (P < 0.01) and remained unchanged in the Plc group (P < 0.05 PIO vs. Plc). EGP did not change, while GNG decreased in the PIO group (9.6 ± 0.7 to 8.7 ± 0.6 µmol · min-1 · kgffm-1) and increased in the Plc group (8.0 ± 0.5 to 9.6 ± 0.8) (P < 0.05 PIO vs. Plc). Change in FPG correlated with change in GNG flux (r = 0.63, P < 0.003) and in insulin sensitivity (r = 0.59, P < 0.01). Plasma adiponectin increased after pioglitazone (P < 0.001) and correlated with FPG (r = -0.54, P < 0.03), GNG flux (r = -0.47, P < 0.05), and insulin sensitivity (r = 0.65, P < 0.005). Plasma free fatty acids decreased after pioglitazone and correlated with GNG flux (r = 0.54, P < 0.02). From stepwise regression analysis, the strongest determinant of change in FPG was change in GNG flux. CONCLUSIONS—Pioglitazone improves FPG, primarily by reducing GNG flux in type 2 diabetic subjects.
URL: http://care.diabetesjournals.org.libproxy.uthscsa.edu/cgi/content/full/29/10/2275
Subject FFA, free fatty acid
FPG, fasting plasma glucose
PPAR, peroxisome proliferator-activated receptor
TZD, thiazolidinedione
FFA, free fatty acid
FPG, fasting plasma glucose
PPAR, peroxisome proliferator-activated receptor
TZD, thiazolidinedione

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