Figure 6.

PPARγ and its targets Pdx1 and SetD7 are downregulated in islets of hyperglycemic 90% Px rats. Rats undergoing sham and 90% Px were supplemented with or without pioglitazone (2.5 mg/kg in a formulated diet) daily for 3 weeks. A, improvement of fed blood glucose levels and glucose tolerance in the 90% Px with pioglitazone compared with 90% Px vehicle group (∗p < 0.004) and as shown by IPGTT curves and corresponding AUC plot (∗p < 0.02). B, RT-PCR gene expression analysis: Total RNA preparations were processed for RT-PCR for the expression of Pdx1, Setd7, and PPARγ using FAM-tagged rat PCR primers. The CT values were normalized with β-actin. Whereas downregulation of Pdx1, Setd7, and PPARγ is observed in islets from 90% Px rats compared with sham controls, pioglitazone supplementation increased Pdx1 mRNA compared with the corresponding sham group and restores the levels of Setd7 and PPARγ to that of the sham group treated with pioglitazone (∗p < 0.005). C, representative confocal immunofluorescence images of pancreatic islets of sham/Px groups ± pioglitazone; Pdx1 (red) and insulin (green) immunostaining demonstrates markedly reduced β-cell Pdx-1 in control 90% Px hyperglycemic rats but enhanced nuclear Pdx1 staining with a pioglitazone-supplemented diet. D, β-cell mass: Pioglitazone intervention in 90% Px rats shows a trend in partially restoring β-cell mass compared with the control 90% Px group. p = 0.09. The data presented represents n = 5 for gene expression, n = 5 for fed glycemia and IPGTT, and n = 3 or 4 for β-cell mass.