| First Author | Fernández AM | Year | 2001 |
| Journal | Genes Dev | Volume | 15 |
| Issue | 15 | Pages | 1926-34 |
| PubMed ID | 11485987 | Mgi Jnum | J:71205 |
| Mgi Id | MGI:2149297 | Doi | 10.1101/gad.908001 |
| Citation | Fernandez AM, et al. (2001) Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes. Genes Dev 15(15):1926-34 |
| abstractText | 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 beta-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. |
