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- Title
Normalization of skeletal muscle glycogen synthesis and glycolysis in rosiglitazone-treated Zucker fatty rats: an in vivo nuclear magnetic resonance study.
- Authors
Jucker, Beat M.; Schaeffer, Thomas R.; Haimbach, Robin E.; McIntosh, Thomas S.; Chun, Daniel; Mayer, Matthew; Ohlstein, Derek H.; Davis, Hugh M.; Smith, Stephen A.; Cobitz, Alexander R.; Sarkar, Susanta K.
- 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 insulin-stimulated glucose disposal in these rats. Metabolic parameters were measured using combined in vivo [sup 13]C nuclear magnetic resonance (NMR) spectroscopy to measure skeletal muscle glucose uptake and its distributed fluxes (glycogen synthesis and glycolysis), and [sup 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. Three groups of Zucker fatty rats (fatty rosiglitazone [FRSG], fatty control [FC], lean control [LC]) were treated for 7 days before the experiment (3 mg/kg rosiglitazone or vehicle via oral gavage). Rates of glycolysis and glycogen synthesis were assessed after treatment by monitoring 1,6-[sup 13]C[sub 2] glucose label incorporation into 1-[sup 13]C glycogen, 3-[sup 13]C lactate, and 3-[sup 13]C alanine during a euglycemic (~7–8 mmol/l)-hyperinsulinemic (10 mU · kg[sup -1] · min[sup -1]) clamp. The FRSG group exhibited a significant increase in insulin sensitivity, reflected by an increased whole-body glucose disposal rate during the clamp (24.4 ± 1.9 vs. 17.6 ± 1.4 and 33.2 ± 2.0 mg · kg[sup -1] · min[sup -1] in FRSG vs. FC [P < 0.05] and LC [P < 0.01] groups, respectively). The increased insulin-stimulated glucose disposal in the FRSG group was associated with a normalization of the glycolytic flux (52.9 ± 9.1) to LC (56.2 ± 16.6) versus FC (18.8 ± 8.6 nmol · g[sup -1] · min[sup -1], P < 0.02) and glycogen synthesis flux (56.3 ± 11.5) to LC (75.2 ± 15.3) versus FC (16.6 ± 12.8 nmol · g[sup -1] · min[sup -1], P < 0.05). [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.
- Subjects
GLYCOGEN synthesis; GLYCOLYSIS; MUSCLES
- Publication
Diabetes, 2002, Vol 51, Issue 7, p2066
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.51.7.2066