The many actions of insulin in skeletal muscle, the paramount tissue determining glycemia

As the principal tissue for insulin-stimulated glucose disposal, skeletal muscle is a primary driver of whole-body glycemic control. Skeletal muscle also uniquely responds to muscle contraction or exercise with increased sensitivity to subsequent insulin stimulation. Insulin's dominating contro...

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Published inCell metabolism Vol. 33; no. 4; pp. 758 - 780
Main Authors Sylow, Lykke, Tokarz, Victoria L., Richter, Erik A., Klip, Amira
Format Journal Article
LanguageEnglish
Published United States 06.04.2021
Subjects
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - pathology
Exercise
Glucose - metabolism
Glucose Transporter Type 4 - metabolism
Humans
Insulin - metabolism
Muscle, Skeletal - metabolism
Oxidative Stress
Receptor, Insulin - metabolism
Signal Transduction
exercise-induced sensitization to insulin
insulin signaling
glucose uptake
insulin
glycogen
GLUT4
skeletal muscle
diabetes
insulin resistance
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Abstract As the principal tissue for insulin-stimulated glucose disposal, skeletal muscle is a primary driver of whole-body glycemic control. Skeletal muscle also uniquely responds to muscle contraction or exercise with increased sensitivity to subsequent insulin stimulation. Insulin's dominating control of glucose metabolism is orchestrated by complex and highly regulated signaling cascades that elicit diverse and unique effects on skeletal muscle. We discuss the discoveries that have led to our current understanding of how insulin promotes glucose uptake in muscle. We also touch upon insulin access to muscle, and insulin signaling toward glycogen, lipid, and protein metabolism. We draw from human and rodent studies in vivo, isolated muscle preparations, and muscle cell cultures to home in on the molecular, biophysical, and structural elements mediating these responses. Finally, we offer some perspective on molecular defects that potentially underlie the failure of muscle to take up glucose efficiently during obesity and type 2 diabetes.
AbstractList As the principal tissue for insulin-stimulated glucose disposal, skeletal muscle is a primary driver of whole-body glycemic control. Skeletal muscle also uniquely responds to muscle contraction or exercise with increased sensitivity to subsequent insulin stimulation. Insulin's dominating control of glucose metabolism is orchestrated by complex and highly regulated signaling cascades that elicit diverse and unique effects on skeletal muscle. We discuss the discoveries that have led to our current understanding of how insulin promotes glucose uptake in muscle. We also touch upon insulin access to muscle, and insulin signaling toward glycogen, lipid, and protein metabolism. We draw from human and rodent studies in vivo, isolated muscle preparations, and muscle cell cultures to home in on the molecular, biophysical, and structural elements mediating these responses. Finally, we offer some perspective on molecular defects that potentially underlie the failure of muscle to take up glucose efficiently during obesity and type 2 diabetes.As the principal tissue for insulin-stimulated glucose disposal, skeletal muscle is a primary driver of whole-body glycemic control. Skeletal muscle also uniquely responds to muscle contraction or exercise with increased sensitivity to subsequent insulin stimulation. Insulin's dominating control of glucose metabolism is orchestrated by complex and highly regulated signaling cascades that elicit diverse and unique effects on skeletal muscle. We discuss the discoveries that have led to our current understanding of how insulin promotes glucose uptake in muscle. We also touch upon insulin access to muscle, and insulin signaling toward glycogen, lipid, and protein metabolism. We draw from human and rodent studies in vivo, isolated muscle preparations, and muscle cell cultures to home in on the molecular, biophysical, and structural elements mediating these responses. Finally, we offer some perspective on molecular defects that potentially underlie the failure of muscle to take up glucose efficiently during obesity and type 2 diabetes.
As the principal tissue for insulin-stimulated glucose disposal, skeletal muscle is a primary driver of whole-body glycemic control. Skeletal muscle also uniquely responds to muscle contraction or exercise with increased sensitivity to subsequent insulin stimulation. Insulin's dominating control of glucose metabolism is orchestrated by complex and highly regulated signaling cascades that elicit diverse and unique effects on skeletal muscle. We discuss the discoveries that have led to our current understanding of how insulin promotes glucose uptake in muscle. We also touch upon insulin access to muscle, and insulin signaling toward glycogen, lipid, and protein metabolism. We draw from human and rodent studies in vivo, isolated muscle preparations, and muscle cell cultures to home in on the molecular, biophysical, and structural elements mediating these responses. Finally, we offer some perspective on molecular defects that potentially underlie the failure of muscle to take up glucose efficiently during obesity and type 2 diabetes.
Author Richter, Erik A.
Tokarz, Victoria L.
Klip, Amira
Sylow, Lykke
Author_xml – sequence: 1
  givenname: Lykke
  orcidid: 0000-0003-0905-5932
  surname: Sylow
  fullname: Sylow, Lykke
– sequence: 2
  givenname: Victoria L.
  surname: Tokarz
  fullname: Tokarz, Victoria L.
– sequence: 3
  givenname: Erik A.
  orcidid: 0000-0002-6850-3056
  surname: Richter
  fullname: Richter, Erik A.
– sequence: 4
  givenname: Amira
  orcidid: 0000-0001-7906-0302
  surname: Klip
  fullname: Klip, Amira
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33826918$$D View this record in MEDLINE/PubMed
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Keywords exercise-induced sensitization to insulin
insulin signaling
glucose uptake
insulin
glycogen
GLUT4
skeletal muscle
diabetes
insulin resistance
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Snippet As the principal tissue for insulin-stimulated glucose disposal, skeletal muscle is a primary driver of whole-body glycemic control. Skeletal muscle also...
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SubjectTerms Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - pathology
Exercise
Glucose - metabolism
Glucose Transporter Type 4 - metabolism
Humans
Insulin - metabolism
Muscle, Skeletal - metabolism
Oxidative Stress
Receptor, Insulin - metabolism
Signal Transduction
Title The many actions of insulin in skeletal muscle, the paramount tissue determining glycemia
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