The effect of pioglitazone on the liver

Role of adiponectin

Amalia Gastaldelli, Yoshinori Miyazaki, Archana Mahankali, Rachele Berria, Maura Pettiti, Emma Buzzigoli, Eleuterio Ferrannini, Ralph A Defronzo

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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 ΔFPG (r = -0.54, P < 0.03), ΔGNG flux (r = -0.47, P < 0.05), and Δinsulin sensitivity (r = 0.65, P < 0.005). Plasma free fatty acids decreased after pioglitazone and correlated with ΔGNG 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.

Original languageEnglish (US)
Pages (from-to)2275-2281
Number of pages7
JournalDiabetes Care
Volume29
Issue number10
DOIs
StatePublished - Oct 2006

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pioglitazone
Gluconeogenesis
Adiponectin
Glucose
Insulin Resistance
Liver
Fasting
Thiazolidinediones
Glucose Clamp Technique

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Gastaldelli, A., Miyazaki, Y., Mahankali, A., Berria, R., Pettiti, M., Buzzigoli, E., ... Defronzo, R. A. (2006). The effect of pioglitazone on the liver: Role of adiponectin. Diabetes Care, 29(10), 2275-2281. https://doi.org/10.2337/dc05-2445

The effect of pioglitazone on the liver : Role of adiponectin. / Gastaldelli, Amalia; Miyazaki, Yoshinori; Mahankali, Archana; Berria, Rachele; Pettiti, Maura; Buzzigoli, Emma; Ferrannini, Eleuterio; Defronzo, Ralph A.

In: Diabetes Care, Vol. 29, No. 10, 10.2006, p. 2275-2281.

Research output: Contribution to journalArticle

Gastaldelli, A, Miyazaki, Y, Mahankali, A, Berria, R, Pettiti, M, Buzzigoli, E, Ferrannini, E & Defronzo, RA 2006, 'The effect of pioglitazone on the liver: Role of adiponectin', Diabetes Care, vol. 29, no. 10, pp. 2275-2281. https://doi.org/10.2337/dc05-2445
Gastaldelli A, Miyazaki Y, Mahankali A, Berria R, Pettiti M, Buzzigoli E et al. The effect of pioglitazone on the liver: Role of adiponectin. Diabetes Care. 2006 Oct;29(10):2275-2281. https://doi.org/10.2337/dc05-2445
Gastaldelli, Amalia ; Miyazaki, Yoshinori ; Mahankali, Archana ; Berria, Rachele ; Pettiti, Maura ; Buzzigoli, Emma ; Ferrannini, Eleuterio ; Defronzo, Ralph A. / The effect of pioglitazone on the liver : Role of adiponectin. In: Diabetes Care. 2006 ; Vol. 29, No. 10. pp. 2275-2281.
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AU - Gastaldelli, Amalia

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AU - Mahankali, Archana

AU - Berria, Rachele

AU - Pettiti, Maura

AU - Buzzigoli, Emma

AU - Ferrannini, Eleuterio

AU - Defronzo, Ralph A

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N2 - 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 ΔFPG (r = -0.54, P < 0.03), ΔGNG flux (r = -0.47, P < 0.05), and Δinsulin sensitivity (r = 0.65, P < 0.005). Plasma free fatty acids decreased after pioglitazone and correlated with ΔGNG 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.

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