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Eckstein, S.S.* ; Weigert, C. ; Lehmann, R.

Divergent roles of IRS (Insulin receptor substrate) 1 and 2 in liver and skeletal muscle.

Curr. Med. Chem. 24, 1827-1852 (2017)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
IRS1 and IRS2 are the most important representatives of the IRS protein family and critical nodes in insulin/IGF1-signaling. Although they are quite similar in their structural and functional features they show tissue-specific differences. In this review, we outline the functions of IRS1 and IRS2 in skeletal muscle and liver with regard to their importance for metabolism, growth and differentiation. Mechanisms contributing to IRS1 and IRS2 dysregulation in disease states as well as consequences thereof are discussed. IRS1 plays the dominant role in skeletal muscle. It is crucial for normal growth and differentiation of myofibers, insulin- dependent glucose uptake and glycogen synthesis. The presence of IRS2 in skeletal muscle is negligible for insulin-induced glucose uptake and the general role of IRS2 in muscle is still not fully understood. In liver IRS1 and IRS2 are important to mediate insulindependent regulation of glucose and lipid metabolism and complement each other in the diurnal regulation thereof. IRS1 in the liver is more important for signaling in the late refeeding period, whereas IRS2 signaling is mostly dominating in the period directly after food intake and during fasting. Importantly, the expression level of IRS1 and IRS2 is different within the liver lobule, which could be an explanation for the phenomenon of selective insulin resistance. Dysregulated muscular or hepatic abundance and/or phosphorylation status of IRS1 and IRS2 are important factors in the pathogenesis of insulin resistance, type 2 diabetes and muscle wasting.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Korrespondenzautor
Schlagwörter Insulin Receptor Substrate ; Skeletal Muscle ; Liver ; Metabolism ; Insulin Resistance ; Phosphorylation ; Degradation; Glycogen-synthase Kinase-3; Forkhead Transcription Factor; Element-binding Protein-1c; Phosphatidylinositol 3-kinase Activity; Stimulated Glucose-transport; C-reactive Protein; Signal-transduction; Serine Phosphorylation; Lipid-metabolism; Nonalcoholic Steatohepatitis
ISSN (print) / ISBN 0929-8673
e-ISSN 1875-533X
Zeitschrift Current Medicinal Chemistry
Quellenangaben Band: 24, Heft: 17, Seiten: 1827-1852 Artikelnummer: , Supplement: ,
Verlag Bentham Science Publishers
Verlagsort Sharjah
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)