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Titolo:
Molecular mechanism of insulin resistance in type 2 diabetes mellitus: role of the insulin receptor variant forms
Autore:
Sesti, G; Federici, M; Lauro, D; Sbraccia, P; Lauro, R;
Indirizzi:
Univ Roma Tor Vergata, Dipartimento Med Interna, Mol Med Lab, I-00133 Rome, Italy Univ Roma Tor Vergata Rome Italy I-00133 ol Med Lab, I-00133 Rome, Italy Univ Catanzaro Magna, Graecia, Italy Univ Catanzaro Magna Graecia ItalyUniv Catanzaro Magna, Graecia, Italy
Titolo Testata:
DIABETES-METABOLISM RESEARCH AND REVIEWS
fascicolo: 5, volume: 17, anno: 2001,
pagine: 363 - 373
SICI:
1520-7552(200109/10)17:5<363:MMOIRI>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-I; GLUCOSE TRANSPORTER GLUT-4; TISSUE-SPECIFIC EXPRESSION; PANCREATIC BETA-CELLS; HYBRID RECEPTORS; SKELETAL-MUSCLE; NIDDM PATIENTS; INCREASED ABUNDANCE; ALTERED EXPRESSION; SPLICED VARIANTS;
Keywords:
type 2 diabetes; insulin receptor isoforms; IGF-I receptor; hybrid receptor; insulin resistance; genetics of type 2 diabetes;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
77
Recensione:
Indirizzi per estratti:
Indirizzo: Sesti, G Univ Roma Tor Vergata, Dipartimento Med Interna, Mol Med Lab, ViaTor Vergata 135, I-00133 Rome, Italy Univ Roma Tor Vergata Via Tor Vergata135 Rome Italy I-00133 aly
Citazione:
G. Sesti et al., "Molecular mechanism of insulin resistance in type 2 diabetes mellitus: role of the insulin receptor variant forms", DIABET M R, 17(5), 2001, pp. 363-373

Abstract

Type 2 diabetes is a heterogeneous and polygenic disorder resulting from interaction of genetic factors with environmental influences. Numerous candidate genes for insulin signaling proteins have been screened, but no singlemajor susceptibility gene for type 2 diabetes has been identified. Due to its pivotal role in insulin action, the insulin receptor was considered a plausible candidate gene. The insulin receptor exists in two isoforms differing by the absence (Ex11(-)) or presence (Ex11(+)) of a 12 amino acid sequence in, the COOH-terminus of the alpha -subunit, as a consequence of alternative splicing of exon 11. The Ex11(-) binds insulin with two-fold higher affinity than the Ex11(+). This difference is paralleled by a decreased sensitivity for metabolic actions of insulin. Some, but not all, studies have reported that expression of the low-affinity Ex11(+) is increased in target tissues from type 2 diabetic patients, thus suggesting that alterations in abundance of the two isoforms might contribute to insulin resistance. Insulin and type 1 IGF receptors have been shown to form hybrid receptors in tissues co-expressing both molecules. Hybrid receptors bind IGF-1, but not insulin, with high affinity, and behave as IGF-1 holoreceptors, rather than insulin receptors, in terms of receptor autophosphorylation, and hormone internalization. it has been shown that the abundance of hybrid receptors is increased in skeletal muscle and adipose tissue from type 2 diabetic patients, and is negatively correlated with in vivo insulin sensitivity. Mutations in the insulin receptor gene have been identified in studies which examinedan appropriately sized population of patients with type 2 diabetes. The prevalence of mutations in the insulin receptor gene ranged from 0.4%-7.8%. This review will focus on the structural and functional heterogeneity of theinsulin receptor, and will discuss the pathogenetic role of insulin receptor variant forms and polymorphisms in the development of the common form oftype 2 diabetes. Copyright (C) 2001 John Wiley & Sons, Ltd.

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Documento generato il 04/04/20 alle ore 11:54:13