Identification and characterization of peroxisome proliferator response element in the mouse GLUT2 promoter

Abstract

A bstractIn the present study, w e show that the expression of type 2 glucose transporter isoform (GLUT2) could be regulated by PPA R -γ in the liver. R osiglitazone, PPA R -γ agonist, activated the G LU T2 m R N A level in the prim ary cultured hepatocytes and Alexander cells, when these cells w ere transfected w ith PPA R -γ/R XR -α. W e have localized the peroxisom e proliferator response elem ent in the m ouse G LUT2 prom oter by serial deletion studies and site-directed m utagenesis. C hrom atin im m unoprecipitation assay using ob/ob m ice also showed that PPAR-γ rather than PPAR-α binds to the -197/-184 region of G LU T2 prom oter. Taken together, liver G LU T2 m ay be a direct target of PPA R -γ lig an d contribu tin g to glu co se tran sport into liver in a condition w hen PA PR -γ expression is increased as in type 2 diabetes or in severe obesity.

Thiazolidinediones inhibit hepatocarcinogenesis in hepatitis B virus–transgenic mice by peroxisome proliferator‐activated receptor γ–independent regulation of nucleophosmin†

“…3A, lanes [5][6][7][8]. The ability of these drugs to modulate PPARc activation was confirmed by the induced expression of GLUT-2, a PPARc target gene, 16 in hepatocytes isolated from both TZD-treated and GW1929-treated mice (Fig. 3B, lanes 1-4).…”

Peroxisome Proliferator-Activated Receptor γ Activation Restores Islet Function in Diabetic Mice through Reduction of Endoplasmic Reticulum Stress and Maintenance of Euchromatin Structure

“…Importantly, Glut2 has been shown to contain PPAR-␥ recognition sequences and is positively regulated by PPAR-␥ agonists (21,26). However, from our studies we cannot know whether increases in the activation of these genes are a direct result of the presence of PPAR-␥ agonists, as these genes are also direct targets of Pdx1 (5,53,55).…”

“…Although thiazolidinediones are classically thought to act as peripheral insulin sensitizers, there is growing evidence from studies of human and animal models that these agents may also act to preserve and/or enhance ␤-cell function in the setting of progressive type 2 diabetes and insulin resistance (3, 12). PPAR-␥ is known to be expressed in the pancreatic islet (8, 48), and PPAR-responsive elements have been identified in the promoters of genes involved in glucose-stimulated insulin secretion, including Glut2, Gck, and Pdx1 (16,21,26,27,33). Reports from studies of ␤-cell lines, rodent models of progressive type 2 diabetes, and humans at risk for type 2 diabetes suggest that PPAR-␥ agonist administration leads to preservation of islet mass and function (10,13,18,22,25,33,57,58).…”

Current Protocols in Mouse Biology

“…Reagents and Solutions: Rosiglitazone maleate (2 mM in 5% BSA and 5% dimethly sulfoxide) diluted to the final concentration of 2 µM as described in (Im et al 2005) Equipment: 18-20 gauge feeding tubes with rounded tip Appropriate housing facility for mice Cages (with bedding, food, and water)…”