Exocytosis Proteins: Typical and Atypical Mechanisms of Action in Skeletal Muscle

Insulin-stimulated glucose uptake in skeletal muscle is of fundamental importance to prevent postprandial hyperglycemia, and long-term deficits in insulin-stimulated glucose uptake underlie insulin resistance and type 2 diabetes. Skeletal muscle is responsible for ~80% of the peripheral glucose upta...

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Bibliographic Details
Published in:Frontiers in endocrinology (Lausanne) 2022-06, Vol.13, p.915509
Main Authors: Hwang, Jinhee, Thurmond, Debbie C
Format: Article
Language:English
Subjects:
Diabetes Mellitus, Type 2 - metabolism
Endocrinology
Exocytosis
Glucose - metabolism
Glucose Transporter Type 4 - metabolism
glucose transporter-4 (GLUT4)
glucose uptake
Humans
Insulin - metabolism
Insulin Resistance
Monosaccharide Transport Proteins - metabolism
Muscle Proteins - metabolism
Muscle, Skeletal - metabolism
skeletal muscle
SNARE protein
SNARE Proteins - metabolism
type 2 diabetes
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Summary:Insulin-stimulated glucose uptake in skeletal muscle is of fundamental importance to prevent postprandial hyperglycemia, and long-term deficits in insulin-stimulated glucose uptake underlie insulin resistance and type 2 diabetes. Skeletal muscle is responsible for ~80% of the peripheral glucose uptake from circulation the insulin-responsive glucose transporter GLUT4. GLUT4 is mainly sequestered in intracellular GLUT4 storage vesicles in the basal state. In response to insulin, the GLUT4 storage vesicles rapidly translocate to the plasma membrane, where they undergo vesicle docking, priming, and fusion the high-affinity interactions among the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) exocytosis proteins and their regulators. Numerous studies have elucidated that GLUT4 translocation is defective in insulin resistance and type 2 diabetes. Emerging evidence also links defects in several SNAREs and SNARE regulatory proteins to insulin resistance and type 2 diabetes in rodents and humans. Therefore, we highlight the latest research on the role of SNAREs and their regulatory proteins in insulin-stimulated GLUT4 translocation in skeletal muscle. Subsequently, we discuss the novel emerging role of SNARE proteins as interaction partners in pathways not typically thought to involve SNAREs and how these atypical functions reveal novel therapeutic targets for combating peripheral insulin resistance and diabetes.
ISSN:1664-2392
1664-2392
DOI:10.3389/fendo.2022.915509