Biomaterial Database

Regulation of excitation contraction coupling by insulin-like growth factor-1 in aging skeletal muscle. 2000

O Delbono

Departments of Physiology and Pharmacology and Internal Medicine, Gerontology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. odelbono@wfubmc.edu

Excitation-contraction (EC) uncoupling is a primary muscle alteration and constitutes a major cause of decline in skeletal muscle force with aging. The structural substratum for EC uncoupling in muscles from aging mammals is a reduction in number of dihydropyridine receptors (DHPR) at the T-tubule and SR membrane leading to an increase in the percent of sarcoplasmic reticulum calcium release channels or ryanodine receptors (RyR1) uncoupled to DHPR. The main functional consequence of this alteration is a failure in the transduction of sarcolemmal depolarization into a calcium signal and a mechanical response. This review summarizes recent studies from our laboratory aimed at elucidating the modulation of EC coupling by insulin-like growth factor-1 (IGF-1) in skeletal muscle. We demonstrated that transgenic overexpression of human IGF-1 exclusively in skeletal muscle increases the number and prevents age-related decline in the number of DHPR. IGF-1 enhances rat skeletal muscle DHPR function and gene expression. The functional significance of these findings is that IGF-1 prevents the age-related decline in muscle force.

UI	MeSH Term	Description	Entries
D007334	Insulin-Like Growth Factor I	A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.	IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D009119	Muscle Contraction	A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009124	Muscle Proteins	The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.	Muscle Protein,Protein, Muscle,Proteins, Muscle
D009133	Muscular Atrophy	Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation.	Atrophy, Muscle,Neurogenic Muscular Atrophy,Neurotrophic Muscular Atrophy,Atrophies, Muscle,Atrophies, Muscular,Atrophies, Neurogenic Muscular,Atrophies, Neurotrophic Muscular,Atrophy, Muscular,Atrophy, Neurogenic Muscular,Atrophy, Neurotrophic Muscular,Muscle Atrophies,Muscle Atrophy,Muscular Atrophies,Muscular Atrophies, Neurogenic,Muscular Atrophies, Neurotrophic,Muscular Atrophy, Neurogenic,Muscular Atrophy, Neurotrophic,Neurogenic Muscular Atrophies,Neurotrophic Muscular Atrophies
D000375	Aging	The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.	Senescence,Aging, Biological,Biological Aging
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012519	Sarcoplasmic Reticulum	A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.	Reticulum, Sarcoplasmic,Reticulums, Sarcoplasmic,Sarcoplasmic Reticulums
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018482	Muscle, Skeletal	A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.	Anterior Tibial Muscle,Gastrocnemius Muscle,Muscle, Voluntary,Plantaris Muscle,Skeletal Muscle,Soleus Muscle,Muscle, Anterior Tibial,Muscle, Gastrocnemius,Muscle, Plantaris,Muscle, Soleus,Muscles, Skeletal,Muscles, Voluntary,Skeletal Muscles,Tibial Muscle, Anterior,Voluntary Muscle,Voluntary Muscles
D019837	Ryanodine Receptor Calcium Release Channel	A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.	Calcium-Ryanodine Receptor Complex,RyR1,Ryanodine Receptor 1,Ryanodine Receptor 2,Ryanodine Receptor 3,Ryanodine Receptors,Ca Release Channel-Ryanodine Receptor,Receptor, Ryanodine,RyR2,RyR3,Ryanodine Receptor,Ca Release Channel Ryanodine Receptor,Calcium Ryanodine Receptor Complex,Complex, Calcium-Ryanodine Receptor,Receptor 1, Ryanodine,Receptor 2, Ryanodine,Receptor 3, Ryanodine,Receptor Complex, Calcium-Ryanodine,Receptors, Ryanodine