Abstract
Both glucose and free fatty acids (FFAs) are used as fuel sources for energy production in a living organism. Compelling evidence supports a role for excess fatty acids synthesized in intramuscular space or dietary intermediates in the regulation of skeletal muscle function. Excess FFA and lipid droplets leads to intramuscular accumulation of lipid intermediates. The resulting downregulation of the insulin signaling cascade prevents the translocation of glucose transporter to the plasma membrane and glucose uptake into skeletal muscle, leading to metabolic disorders such as type 2 diabetes. The mechanisms underlining metabolic dysfunction in skeletal muscle include accumulation of intracellular lipid derivatives from elevated plasma FFAs. This paper provides a review of the molecular mechanisms underlying insulin-related signaling pathways after excess accumulation of lipids.
Highlights
Skeletal muscle is thought to be the primary organ responsible for insulin-stimulated glucose tolerance; the resistant response of skeletal muscle to insulin stimulation is considered a key step in the progress of metabolic diseases [1]
The uptake of circulating free fatty acid (FFA) by the liver, skeletal muscle, and other tissues is a main step in lipid storage and mobilization
FFAs are the substrates in that respond to insulin signaling
Summary
Skeletal muscle is thought to be the primary organ responsible for insulin-stimulated glucose tolerance; the resistant response of skeletal muscle to insulin stimulation is considered a key step in the progress of metabolic diseases [1]. Glucose uptake stimulated by insulin leads to increased lipogenesis and glycogen and protein synthesis, and it inhibits lipolysis, glycogenolysis, and protein breakdown in skeletal muscle [5,6]. 3-kinase signaling, knock-out of SKIP in havecauses clarified that the insulin resistance in skeletal muscle involved the intracellular accumulation of lipid mice increased signaling, leading to enhanced glucose uptake in the skeletal muscle derivatives, such as DAG and ceramides, which are closely associated with elevated plasma free fatty [24]. In skeletal muscle fromcoordinating type 2 diabetic patients, IRS-1demands tyrosine among phosphorylation, 3-kinase activity, maintenance requires systemic energy tissues thatPIstore or use energy and glucose transport activity were impaired, whereas insulin receptor tyrosine phosphorylation, substrates, carbohydrates, and lipids. Insulin-resistant, majority of insulin-stimulated uptake occurs skeletal muscle.
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