Metabolic Profile and Nitric Oxide Synthase Expression of Skeletal Muscle Fibers are Altered in Patients with Type 1 Diabetes

Abstract

We investigate muscle fiber composition, fiber-specific glycolytic and oxidative enzyme capacity and nitric oxide synthase (NOS) expression in skeletal muscle of patients with type 1 diabetes (T1D) compared to individuals with normal glucose tolerance (NGT). Vastus lateralis muscle was obtained by percutaneous biopsy from 7 T1D patients and 10 healthy controls with similar characteristics. Using cytophotometry, muscle fiber composition and fiber type-specific glycolytic and oxidative enzyme activities were measured in slow oxidative (SO), fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibers. In addition, NOS 1-3 protein expression was mea-sured. The glycolytic fiber fraction was 1.4 fold higher, whereas FOG and SO fiber fractions were significantly reduced by 13.5% and 6.2% in skeletal muscle from T1D patients. Glycolytic enzyme activities and fiber-specific ratio of glycolytic relative to oxidative enzyme activity were significantly higher in all fiber types of T1D patients and correlated with HbA (1c). Expression of NOS1-3 isoforms was reduced in skeletal muscle of T1D subjects. Increased glycolytic enzyme activity in muscle of T1D patients is most likely due to both a higher number of fast glycolytic fibers and a shift towards increased glycolytic metabolism in all fiber types. Alterations in muscle fiber distribution and enzyme activities seem to be due to impaired long-term glycemic control.

Impaired Growth and Force Production in Skeletal Muscles of Young Partially Pancreatectomized Rats: A Model of Adolescent Type 1 Diabetic Myopathy?

“…Consistent with studies using STZ rodents that report reductions in oxidative capacity [62], [64], [65], we also found reductions in SDH and COX activity in the GP muscles in the 8 week Px group. Despite these reductions in oxidative enzymes, we observed attenuation in relative muscular fatigue rates at both 4 and 8 weeks after Px- compared to Sham- surgery (Figure 2 inset).…”

“…type IIb/d fibers), which is indeed counter to what we have speculated to have occurred in these animals. It may be that the small reduction in peak twitch amplitude at 8 weeks might explain the reduced contraction and relaxation time in these animals, although an increase in the number of type II fibers (although with reduced fiber areas) with T1DM, as has been observed in human studies of T1DM [62], [63], can not be ruled out.…”

Diabetic myopathy: impact of diabetes mellitus on skeletal muscle progenitor cells

“…Muscle growth and development is significantly impaired in T1DM, resulting in reduced muscle mass and myofiber size, poor metabolic control, and a switch to a glycolytic phenotype (Andersen et al, 1997, 2004; Crowther et al, 2003; Fritzsche et al, 2008; Krause et al, 2009, 2013). While initial studies in human T1DM reported no difference in capillary density (Leinonen et al, 1982), investigations in T1DM mice illustrate that the disease is associated with a decline in skeletal muscle capillarization and angiogenesis (Kivelä et al, 2006; Krause et al, 2009).…”

Mitochondrial capacity is affected by glycemic status in young untrained women with type 1 diabetes but is not impaired relative to healthy untrained women

“…Some authors report decreased peak oxygen uptake and/or reduced submaximal cardiac output (15,24,27), yet, other investigators showed that peak oxygen uptake is not affected in patients with type 1 diabetes (13,17,37). However, none of these authors have concurrently investigated both skeletal muscle structure and in vivo (mitochondrial) function and combined these data with the functional assessment of peak oxygen uptake and peak cardiac output.…”