Automated Methods for the Analysis of Skeletal Muscle Fiber Size and Metabolic Type - International Review of Cell and Molecular Biology - page 277

patients could not be assigned to known mutations ( Clement et al., 2012 ),
illustrating the lack of understanding of these afflictions. Limb-girdle mus-
cular dystrophies (LGMD) are similar to the CMD in that they occur rarely
and are due to mutations in calpain-3, dysferlin, isoforms of sarcoglycan,
fukutin, and fukutin-related protein, and others. The mutations responsible
for LGMD are unknown for approximately 37% of the LGMD patients
( Rosales and Tsao, 2012 ). LGMD initially presents as weakness of the prox-
imal muscle groups, particularly in the pelvic girdle, followed later by weak-
ness in the shoulder girdle, and is generally not fatal. Other muscular
dystrophies include oculopharyngeal muscular dystrophy, caused by a muta-
tion in polyadenylate-binding protein nuclear 1 gene (PABPN1) which
weakens the muscles of the eyelids and pharynx leading to dropping of
the eyelids and difficulty with swallowing ( Ruegg et al., 2005 ); myotonic
dystrophies, in which it is difficult to relax muscles due to mutations in
dystrophia myotonica-protein kinase ( Romeo, 2012 ); and distal myopa-
thies, in which weakness develops in the feet and hands, which are due
to mutations in at least 14 different proteins ( Udd, 2012 ). Myofibrillar
myopathies represent another disease group, characterized by disorganized
muscle fibers and inappropriate accumulations of muscle proteins due to
mutations in alphaB-crystalin, Zasp, or Bag3 ( Selcen, 2010 ).
2.7. Diabetes
The development of obesity leads to elevation of plasma fatty acids,
increased fat content of skeletal muscle, and insensitivity to insulin-mediated
glucose uptake into the muscle; this, in turn, leads to increased glucose in the
plasma and development of Type II (adult-onset) diabetes ( Eckardt et al.,
2011; Guo, 2007 ). While these relationships initially appear related in a sim-
ple manner, the mechanisms via which insulin resistance is acquired are
complex and remain to be fully elucidated. For example, while triglyceride
containing lipid droplets are found in skeletal muscle and are elevated in
muscle of insulin-resistant subjects, particularly within the Type I fibers,
insulin resistance may correlate more closely with lipid metabolites such
as ceramide or diacylglycerol rather than overall muscle triglyceride content
( Coen et al., 2010 ). There are also alterations in fiber-type expression and
metabolism associated with diabetes. For example, for human diabetic
patients, the proportion of slow (Type I) fibers within the vastus lateralis
muscle is reduced ( Gaster et al., 2001 ) and there is upregulation of both gly-
colytic and oxidative enzymes within the fast (Type II fibers) ( Oberbach