2011 ADA Posters 1261-2041.indd - Diabetes

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