Background:

Pioglitazone (U 72107) is a potent and selective PPARγ agonist with high affinity binding to the PPARγ ligand-binding domain with EC50 of 0.93 and 0.99 μM for human and mouse PPARγ, respectively.

AGEs-induced beta cell necrosis is completely abrogated by adding Pioglitazone (U 72107) to the AGEs culture medium. Furthermore Pioglitazone completely prevented any AGEs-induced increment in caspase-3 activation, thereby restoring caspase-3 activity to the same levels as the control cells. As expected AG is able to counteract AGEs-induced impaired viability[2].

The serum-free fatty acid and triglyceride levels as well as adipocyte sizes in ob/ob and adipo-/- ob/ob mice are unchanged after 10 mg/kg Pioglitazone (U 72107) but are significantly reduced to a similar degree after 30 mg/kg Pioglitazone. Moreover, the expressions of TNFα and resistin in adipose tissues of ob/ob and adipo-/- ob/ob mice are unchanged after 10 mg/kg Pioglitazone but are decreased after 30 mg/kg Pioglitazone. Thus, Pioglitazone-induced amelioration of insulin resistance and diabetes may occur adiponectin dependently in the liver and adiponectin independently in skeletal muscle[3].Pioglitazone (10 mg/kg per d) treatment significantly attenuates the loss of body weight (BW) and cardiac hypertrophy. Pioglitazone treatment significantly reduces the elevated serum glucose levels and markedly improved the associated dyslipidemia. Furthermore, there is a slight but significant increase in serum creatinine level in D rats over their N controls (P<0.05). However, a marked renal dysfunction is observed in diabetic nephropathic (DN) group (P<0.05). Moreover, DN rats exhibits the highest serum activity of CK-MB, relative to both N and D rats (P<0.05). Pioglitazone is able to decrease the elevated serum levels of both creatinine and creatine kinase-MB (CK-MB)[4].

参考文献:
[1]. Kuwabara K, et al. A novel selective peroxisome proliferator-activated receptor alpha agonist, 2-methyl-c-5-[4-[5-methyl-2-(4-methylphenyl)-4-oxazolyl]butyl]-1,3-dioxane-r-2-carboxylic acid (NS-220), potently decreases plasma triglyceride and glucose leve
[2]. Puddu A, et al. Pioglitazone attenuates the detrimental effects of advanced glycation end-products in the pancreatic beta cell line HIT-T15. Regul Pept. 2012 Aug 20;177(1-3):79-84.
[3]. Kubota N, et al. Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways. J Biol Chem. 2006 Mar 31;281(13):8748-55.
[4]. Elrashidy RA, et al. Pioglitazone attenuates cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy. J Cardiovasc Pharmacol Ther. 2012 Sep;17(3):324-33.