Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes

A. M. Fernández, J. K. Kim, Shoshana Yakar, J. Dupont, C. Hernandez-Sanchez, A. L. Castle, J. Filmore, G. I. Shulman, D. Le Roith

Research output: Contribution to journalArticle

Abstract

Peripheral insulin resistance and impaired insulin action are the primary characteristics of type 2 diabetes. The first observable defect in this major disorder occurs in muscle, where glucose disposal in response to insulin is impaired. We have developed a transgenic mouse with a dominant-negative insulin-like growth factor-I receptor (KR-IGF-IR) specifically targeted to the skeletal muscle. Expression of KR-IGF-IR resulted in the formation of hybrid receptors between the mutant and the endogenous IGF-I and insulin receptors, thereby abrogating the normal function of these receptors and leading to insulin resistance. Pancreatic β-cell dysfunction developed at a relative early age, resulting in diabetes. These mice provide an excellent model to study the molecular mechanisms underlying the development of human type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)1926-1934
Number of pages9
JournalGenes & development
Volume15
Issue number15
DOIs
StatePublished - Aug 1 2001

Fingerprint

IGF Type 1 Receptor
Insulin Receptor
Type 2 Diabetes Mellitus
Insulin Resistance
Skeletal Muscle
Insulin
Human Development
Vascular Resistance
Transgenic Mice
Glucose
Muscles

Keywords

  • Dominant-negative
  • IGF-I receptor
  • Insulin receptor
  • Skeletal muscle
  • Transgenic
  • Type 2 diabetes

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Fernández, A. M., Kim, J. K., Yakar, S., Dupont, J., Hernandez-Sanchez, C., Castle, A. L., ... Le Roith, D. (2001). Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes. Genes & development, 15(15), 1926-1934. https://doi.org/10.1101/gad.908001

Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes. / Fernández, A. M.; Kim, J. K.; Yakar, Shoshana; Dupont, J.; Hernandez-Sanchez, C.; Castle, A. L.; Filmore, J.; Shulman, G. I.; Le Roith, D.

In: Genes & development, Vol. 15, No. 15, 01.08.2001, p. 1926-1934.

Research output: Contribution to journalArticle

Fernández, AM, Kim, JK, Yakar, S, Dupont, J, Hernandez-Sanchez, C, Castle, AL, Filmore, J, Shulman, GI & Le Roith, D 2001, 'Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes', Genes & development, vol. 15, no. 15, pp. 1926-1934. https://doi.org/10.1101/gad.908001
Fernández, A. M. ; Kim, J. K. ; Yakar, Shoshana ; Dupont, J. ; Hernandez-Sanchez, C. ; Castle, A. L. ; Filmore, J. ; Shulman, G. I. ; Le Roith, D. / Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes. In: Genes & development. 2001 ; Vol. 15, No. 15. pp. 1926-1934.
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