Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle

markers or mediators of insulin resistance in type 2 diabetes?

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: Nov
OriginalsprogEngelsk
TidsskriftCurrent Diabetes Reviews
Vol/bind2
Udgave nummer4
Sider (fra-til)375-395
Antal sider20
ISSN1573-3998
DOI
StatusUdgivet - 2006

Fingeraftryk

Glycogen Synthase
Type 2 Diabetes Mellitus
Insulin Resistance
Skeletal Muscle
Insulin
Muscles
Phospho-Specific Antibodies
Oxidative Phosphorylation
Lipids

Citer dette

@article{aeee80d0cbef11dbbc51000ea68e967b,
title = "Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle: markers or mediators of insulin resistance in type 2 diabetes?",
abstract = "Insulin resistance in skeletal muscle is a major hallmark of type 2 diabetes and an early detectable abnormality in the development of this disease. The cellular mechanisms of insulin resistance include impaired insulin-mediated muscle glycogen synthesis and increased intramyocellular lipid content, whereas impaired insulin activation of muscle glycogen synthase represents a consistent, molecular defect found in both type 2 diabetic and high-risk individuals. Despite several studies of the insulin signaling pathway believed to mediate dephosphorylation and hence activation of glycogen synthase, the molecular mechanisms responsible for this defect remain unknown. Recently, the use of phospho-specific antibodies in human diabetic muscle has revealed hyperphosphorylation of glycogen synthase at sites not regulated by the classical insulin signaling pathway. In addition, novel approaches such as gene expression analysis and proteomics have pointed to abnormalities in mitochondrial oxidative phosphorylation and cellular stress in muscle of type 2 diabetic subjects, and recent work suggests that impaired mitochondrial activity is another early defect in the pathogenesis of type 2 diabetes. This review will discuss the latest advances in the understanding of the molecular mechanisms underlying insulin resistance in human skeletal muscle in type 2 diabetes with focus on possible links between impaired glycogen synthase activity and mitochondrial dysfunction.",
keywords = "Diabetes Mellitus, Type 2, Glucose Transporter Type 4, Glycogen Synthase, Glycogen Synthase Kinase 3, Humans, Insulin, Insulin Resistance, Mitochondria, Muscle, Skeletal, Proteome, Signal Transduction",
author = "Kurt H{\o}jlund and Henning Beck-Nielsen",
year = "2006",
doi = "10.2174/1573399810602040375",
language = "English",
volume = "2",
pages = "375--395",
journal = "Current Diabetes Reviews",
issn = "1573-3998",
publisher = "Bentham Science Publishers Ltd.",
number = "4",

}

TY - JOUR

T1 - Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle

T2 - markers or mediators of insulin resistance in type 2 diabetes?

AU - Højlund, Kurt

AU - Beck-Nielsen, Henning

PY - 2006

Y1 - 2006

N2 - Insulin resistance in skeletal muscle is a major hallmark of type 2 diabetes and an early detectable abnormality in the development of this disease. The cellular mechanisms of insulin resistance include impaired insulin-mediated muscle glycogen synthesis and increased intramyocellular lipid content, whereas impaired insulin activation of muscle glycogen synthase represents a consistent, molecular defect found in both type 2 diabetic and high-risk individuals. Despite several studies of the insulin signaling pathway believed to mediate dephosphorylation and hence activation of glycogen synthase, the molecular mechanisms responsible for this defect remain unknown. Recently, the use of phospho-specific antibodies in human diabetic muscle has revealed hyperphosphorylation of glycogen synthase at sites not regulated by the classical insulin signaling pathway. In addition, novel approaches such as gene expression analysis and proteomics have pointed to abnormalities in mitochondrial oxidative phosphorylation and cellular stress in muscle of type 2 diabetic subjects, and recent work suggests that impaired mitochondrial activity is another early defect in the pathogenesis of type 2 diabetes. This review will discuss the latest advances in the understanding of the molecular mechanisms underlying insulin resistance in human skeletal muscle in type 2 diabetes with focus on possible links between impaired glycogen synthase activity and mitochondrial dysfunction.

AB - Insulin resistance in skeletal muscle is a major hallmark of type 2 diabetes and an early detectable abnormality in the development of this disease. The cellular mechanisms of insulin resistance include impaired insulin-mediated muscle glycogen synthesis and increased intramyocellular lipid content, whereas impaired insulin activation of muscle glycogen synthase represents a consistent, molecular defect found in both type 2 diabetic and high-risk individuals. Despite several studies of the insulin signaling pathway believed to mediate dephosphorylation and hence activation of glycogen synthase, the molecular mechanisms responsible for this defect remain unknown. Recently, the use of phospho-specific antibodies in human diabetic muscle has revealed hyperphosphorylation of glycogen synthase at sites not regulated by the classical insulin signaling pathway. In addition, novel approaches such as gene expression analysis and proteomics have pointed to abnormalities in mitochondrial oxidative phosphorylation and cellular stress in muscle of type 2 diabetic subjects, and recent work suggests that impaired mitochondrial activity is another early defect in the pathogenesis of type 2 diabetes. This review will discuss the latest advances in the understanding of the molecular mechanisms underlying insulin resistance in human skeletal muscle in type 2 diabetes with focus on possible links between impaired glycogen synthase activity and mitochondrial dysfunction.

KW - Diabetes Mellitus, Type 2

KW - Glucose Transporter Type 4

KW - Glycogen Synthase

KW - Glycogen Synthase Kinase 3

KW - Humans

KW - Insulin

KW - Insulin Resistance

KW - Mitochondria

KW - Muscle, Skeletal

KW - Proteome

KW - Signal Transduction

U2 - 10.2174/1573399810602040375

DO - 10.2174/1573399810602040375

M3 - Journal article

VL - 2

SP - 375

EP - 395

JO - Current Diabetes Reviews

JF - Current Diabetes Reviews

SN - 1573-3998

IS - 4

ER -