Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.3.5.1 (
succinate dehydrogenase
)
8,177
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Resistance to the anabolic effects of growth hormone (GH) occurs with severe caloric deficit. This study examined whether moderate caloric deficit (50% of daily intake for 7 days) in the adolescent rat exceeds a critical threshold for GH action and whether a combination of GH and
insulin-like growth factor I
(
IGF-I
) would have enhanced anabolic effects on the diaphragm (Dia). Five groups of rats (4 wk old) were studied: 1) control (Ctl), 2) nutritionally deprived (ND), 3) ND + GH, 4) ND +
IGF-I
, and 5) ND + GH +
IGF-I
.
IGF-I
was given by continuous infusion (200 microg/day). GH was injected subcutaneously (250 microg every 12 h). Contractile and fatigue properties of the Dia were determined in vitro. Quantitative histochemical methods were used to determine Dia fiber type proportions, cross-sectional areas, and
succinate dehydrogenase
activities. The body weight of Ctl rats increased 46% compared with 7% in ND animals, whereas that of ND rats receiving growth factors was intermediate. Serum
IGF-I
levels were reduced 54% in ND animals and maintained with the provision of growth factors. Dia fatigue resistance was improved in ND animals receiving growth factors. There were no differences in Dia contractile properties, fiber type proportions, or
succinate dehydrogenase
activities across groups. ND resulted in atrophy/growth arrest of all Dia fibers (20-32%) compared with Ctl. Administration of
IGF-I
and/or GH completely prevented atrophy/growth arrest of all Dia fibers. No additive or synergistic effects were noted. We propose that these growth factors may provide useful short-term adjunctive nutritional support in circumstances in which the provision of optimal nutrition may be delayed or inadequate.
...
PMID:IGF-I and/or growth hormone preserve diaphragm fiber size with moderate malnutrition. 965 74
The impact of a targeted disruption of the Igf1 gene, encoding the
insulin-like growth factor I
(
IGF-I
), on diaphragm (DIA) cellularity was studied in 2-mo-old homozygous mutant [
IGF-I
(-/-)] mice and their wild-type [WT; i.e.,
IGF-I
(+/+)] littermates. DIA fiber types were classified histochemically. DIA fiber cross-sectional areas (CSA) were determined from digitized muscle sections, and fiber
succinate dehydrogenase
(
SDH
) activity was determined histochemically using a microdensitometric procedure. An acidic ATPase reaction was used to visualize capillaries. Myosin heavy chain (MyHC) isoforms were identified by SDS-PAGE, and their proportions were determined by scanning densitometry. The body weight of
IGF-I
(-/-) animals was 32% that of WT littermates. DIA fiber type proportions were unchanged between the groups. The CSAs of types I, IIa, and IIx DIA fibers of
IGF-I
(-/-) mutants were 63, 68, and 65%, respectively, those of WT animals (P < 0.001). The DIA thickness and the number of fibers spanning its entire thickness were reduced by 36 and 25%, respectively, in
IGF-I
(-/-) mice (P < 0. 001).
SDH
activity was significantly increased in all three types of DIA fibers of
IGF-I
(-/-) mutants (P < 0.05). The number of capillaries per fiber was reduced approximately 30% in
IGF-I
(-/-) animals, whereas the capillary density was preserved. The proportions of MyHC isoforms were similar between the groups. Muscle hypoplasia likely reflects the importance of
IGF-I
on cell proliferation, differentiation, and apoptosis (alone or in combination) during development, although reduced cell size highlights the importance of
IGF-I
on rate and/or maintenance of DIA fiber growth in the postnatal state. Reduced capillarity may result from both direct and indirect influences on angiogenesis. Improved oxidative capacity likely reflects DIA compensatory mechanisms in
IGF-I
(-/-) mutants.
...
PMID:Influences of IGF-I gene disruption on the cellular profile of the diaphragm. 1075 Dec 6
Limited knowledge exists regarding the efficacy of
insulin-like growth factor I
(
IGF-I
) administration as a therapeutic intervention for muscular dystrophies, although findings from other muscle pathology models suggest clinical potential. The diaphragm muscles of mdx mice (a model for Duchenne muscular dystrophy) were examined after 8 weeks of
IGF-I
administration (1 mg/kg s.c.) to test the hypothesis that
IGF-I
would improve the functional properties of dystrophic skeletal muscles. Force per cross-sectional area was approximately 49% greater in the muscles of treated mdx mice (149.6 +/- 9.6 kN/m(2)) compared with untreated mice (100.1 +/- 4.6 kN/m(2), P < 0.05), and maintenance of force over repeated maximal contraction was enhanced approximately 30% in muscles of treated mice (P < 0.05). Diaphragm muscles from treated mice comprised fibers with approximately 36% elevated activity of the oxidative enzyme
succinate dehydrogenase
, and approximately 23% reduction in the proportion of fast IId/x muscle fibers with concomitant increase in the proportion of type IIa fibers compared with untreated mice (P < 0.05). The data demonstrate that
IGF-I
administration can enhance the fatigue resistance of respiratory muscles in an animal model of dystrophin deficiency, in conjunction with enhancing energenic enzyme activity. As respiratory function is a mortality predictor in Duchenne muscular dystrophy patients, further evaluation of
IGF-I
intervention is recommended.
...
PMID:Improved contractile function of the mdx dystrophic mouse diaphragm muscle after insulin-like growth factor-I administration. 1246 40
