2011 ADA Posters 1261-2041.indd - Diabetes

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of genetically obese and diabetic (ob/ob) mice display a 50% size reduction and a dramatic lipid accumulation as compared to lean mice. To determine whether activation of Wnt signaling could improve lipid deposition in vivo, we performed a direct electrotransfection of Wnt10b cDNA or injected BIO in Tibialis Anterior (TA) muscles of ob/ob mice. Both up-regulated Wnt10b and down-regulated SREBP-1c proteins 21 days later, then inducing a drastic decrease in lipid deposition. Furthermore, mitochondrial Succinic DeHydrogenase (SDH) staining showed that Wnt signaling increased oxidative fi bers number by 12% ± 3% in TA of ob/ob mice, while decreasing glycolytic fi bers of the same amount, the size and total number of fi bers remaining unchanged. Immunostaining of TA slices using antibodies raised against the slow myosin MyhcI isoform and the fast MyhcIIA isoform (the most oxidative among fast isoforms) showed a 16% ± 4% increase in oxidative fi bers number, the number of glycolytic fi bers being decreased of the same amount. Our results show that activation of Wnt/β-catenin signaling in human and mouse skeletal muscle not only decreased lipid deposition, but also induced a shift towards oxydative MyHC-expressing fi bers, leading to improved insulin sensitivity. Supported by: AFM & 1727-P Mitochondrial Defi ciency of Aging Is Not Associated with Insulin Resistance or Higher Intramyocellular Lipid Storage FREDERICO G.S. TOLEDO, BRET H. GOODPASTER, PETER CHOMENTOWSKI III, Pittsburgh, PA In young adults, insulin resistance has been associated with lower mitochondrial oxidative capacity in skeletal muscle. This association suggests a defi ciency in mitochondria that may promote intramyocellular lipid (IMCL) deposition and insulin resistance. However, whether a defi ciency in mitochondria by itself is suffi cient to promote IMCL excess and insulin resistance in humans has not been established. Aging is associated with a decline in mitochondrial content and thus it is plausible that older adults with a decline in mitochondria should express higher IMCL accumulation and insulin resistance. To test this hypothesis, we studied the skeletal muscle mitochondrial content of younger and older adults as it relates to IMCL content and insulin sensitivity. Non-diabetic, middle-age (30-55 years-old) and older adults (>65) were divided into insulin-sensitive (IS) and resistant (IR) groups (Younger-IS, Younger-IR, Old-IS, and Old-IR). Euglycemic clamps were used to measure insulin sensitivity defi ned as glucose disposal (mg/ kgFFM/min). Quantitative analysis of electron micrographs of skeletal muscle biopsies was used to measure mitochondrial and IMCL content. In the IR groups, glucose disposal was nearly half of the respective IS groups (Younger: 5.8 vs 12.1; Old: 4.7 vs 10.7, P
Integrated Physiology/ Obesity POSTERS 28±6% of basal blood glucose, STZ-KO 42±7% of basal blood glucose, p
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2011 ADA Posters 1261-2041.indd - Diabetes

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