Normalization of Skeletal Muscle Glycogen Synthesis and Glycolysis in Rosiglitazone-Treated Zucker Fatty Rats

Abstract

The aim of this study was to characterize insulin-stimulated skeletal muscle glucose metabolism in Zucker fatty rats and to provide insight into the therapeutic mechanism by which rosiglitazone increases insulinstimulated glucose disposal in these rats. Metabolic parameters were measured using combined in vivo 13 C nuclear magnetic resonance (NMR) spectroscopy to measure skeletal muscle glucose uptake and its distributed fluxes (glycogen synthesis and glycolysis), and 31 P NMR was used to measure simultaneous changes in glucose-6-phosphate (G-6-P) during a euglycemic-hyperinsulinemic clamp in awake Zucker fatty rats. [G-6-P] increased in the FRSG and LC groups versus baseline during the clamp (13.0 ؎ 11.1 and 16.9 ؎ 5.8%, respectively), whereas [G-6-P] in the FC group decreased (؊23.3 ؎ 13.4%, P < 0.05). There were no differences between groups in intramyocellular glucose, as measured by biochemical assay. These data suggest that the increased insulin-stimulated glucose disposal in muscle after rosiglitazone treatment can be attributed to a normalization of glucose transport and metabolism.

Rosiglitazone Restores G-Protein Coupling, Recruitment, and Function of Renal Dopamine D 1A Receptor in Obese Zucker Rats

“…11,29,30 However, the present study as well as some recent reports show that even lower doses (3 to 5 mg/kg per day) of rosiglitazone for 7 to 14 days improve insulin sensitivity to the same extent. [31][32][33] In obese rats, fasting blood glucose levels were completely normalized to levels seen in lean rats, and plasma insulin values were reduced to similar extent with both treatment regimens of rosiglitazone.…”

Divergent effects of rosiglitazone on protein-mediated fatty acid uptake in adipose and in muscle tissues of Zucker rats

“…This increased plasma cholesterol was equally distributed among the three different lipoprotein fractions (i.e., VLDL, LDL, and HDL) (data not shown). These effects of Rgz are characteristic of the treatment of insulin resistance with PPAR ␥ agonists in rodent and human studies (2,3,(25)(26)(27).…”

“…Several studies with insulinresistant rodent models and type 2 diabetic patients have demonstrated that TZD treatment reduces both hyperinsulinemia and hyperlipidemia (1)(2)(3)(4)(5). Another important effect of TZDs is the normalization of insulin-stimulated whole-body glucose disposal, as reflected by an improved insulin action on skeletal muscle (2) and heart (4). TZDs are agonists of the peroxisome proliferator-activated receptor ␥ (PPAR ␥ ) (6,7).…”

In Vivo Heteronuclear Magnetic Resonance Spectroscopy

“…We obtain a total bolus of 0.423 g/kg. To transform expression 8 into volume values, we will consider an estimated glucose disposal rate (eGDR) of 33.2 mg/kg/min [36], duration of the bolus of 5 min, and a glucose solution of 200 g/L. The total volume can be calculated as shown in Eq.…”