PreprintCited by 369Metabolism, Diabetes, and CancerGrowth Hormone and Insulin-like Growth FactorsPancreatic function and diabetes

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

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Fernández, Ana M., Kim, Jason K., Yakar, Shoshana, Dupont, Joëlle, Hernandez-Sanchez, Catalina, Castle, Arthur L., Filmore, Jonathan, Shulman, Gerald I., Le Roith, Derek·2001·Genes & Development

DOI 10.1101/gad.908001PMC PMC312754

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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 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.

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Lillioja, S., Mott, D. M., Spraul, M., Ferraro, R., Foley, J. E., Ravussin, E., Knowler, W. C., Bennett, P. H., & Bogardus, C. (1993) · New England Journal of Medicine · doi:10.1056/nejm199312303292703 · Cited by 1,508
Molecular and Cellular Aspects of the Insulin-Like Growth Factor I Receptor
LeRoith, D., Werner, H., Beitner‐Johnson, D., & Roberts, C. T. (1995) · Endocrine Reviews · doi:10.1210/edrv-16-2-143 · Cited by 1,424
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Normal growth and development in the absence of hepatic insulin-like growth factor I
Yakar, S., Liu, J., STANNARD, B. S., Butler, A. A., Accili, D., Sauer, B., & LeRoith, D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.13.7324 · Cited by 1,418
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Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction.
Michael, M. D., Kulkarni, R. N., Postic, C., Previs, S. F., Shulman, G. I., Magnuson, M. A., & Kahn, C. R. (2000) · Molecular Cell · doi:10.1016/s1097-2765(05)00015-8 · Cited by 1,296
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Shulman, G. I., Rothman, D. L., Jue, T., Stein, P., DeFronzo, R. A., & Shulman, R. G. (1990) · New England Journal of Medicine · doi:10.1056/nejm199001253220403 · Cited by 1,248
Self-citation
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Brüning, J. C., Michael, M. D., Winnay, J. N., Hayashi, T., Hörsch, D., Accili, D., Goodyear, L. J., & Kahn, C. R. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80155-0 · Cited by 1,173
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Kulkarni, R., Brüning, J. C., Winnay, J. N., Postic, C., Magnuson, M. A., & Kahn, C. R. (1999) · Cell · doi:10.1016/s0092-8674(00)80546-2 · Cited by 1,148
Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance
Zisman, A., Peroni, O. D., Abel, E. D., Michael, M. D., Mauvais-Jarvis, F., Lowell, B. B., Wojtaszewski, J. F. P., Hirshman, M. F., Virkamaki, A., Goodyear, L. J., et al. (2000) · Nature Medicine · doi:10.1038/78693 · Cited by 743
Untitled work
(1997) · Diabetes reviews · Cited by 671
Early neonatal death in mice homozygous for a null allele of the insulin receptor gene
Accili, D., Drago, J., Lee, E. J., Johnson, M. D., Cool, M. H., Salvatore, P., Asico, L. D., José, P. A., Taylor, S. I., & Westphal, H. (1996) · Nature Genetics · doi:10.1038/ng0196-106 · Cited by 594

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Authors: Fernández, A. M., Kim, J. K., Yakar, S., Dupont, J., Hernandez-Sanchez, C., Castle, A. L., Filmore, J., Shulman, G. I., & Le Roith, D.
Affiliations: National Institutes of Health (US)
ORCID: Kim, Jason K.
Yakar, Shoshana
Dupont, Joëlle
Shulman, Gerald I.
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 2001-08-01
Volume: 15
Issue: 15
Pages: 1926-1934
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.908001
PMC: PMC312754
OpenAlex: W2125231550
Cited by: 369
References: 33
Citations by year: 2026: 5 · 2025: 4 · 2024: 8 · 2023: 14 · 2022: 11 · 2021: 18 · 2020: 15 · 2019: 7 · 2018: 7 · 2017: 12 · 2016: 16 · 2015: 25 · 2014: 15 · 2013: 13 · 2012: 19
Type: posted content
Language: en
Open access: hybrid
doi.org
Licence: other-oa
Locations: Genes & Development (publishedVersion, other-oa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion, other-oa)
DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Funders: Howard Hughes Medical Institute
Ministerio de Educación y Cultura
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080756, R01DK040936)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Keywords: type 2 diabetes, insulin resistance, IGF-1 receptor, insulin receptor, skeletal muscle, dominant negative receptor, hybrid receptors, transgenic mouse model, beta-cell dysfunction, glucose disposal
MeSH terms: Insulin Secretion, Aging, Animals, Blood Glucose, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Glucose, Humans, Hyperinsulinism, Insulin, Insulin Resistance, Islets of Langerhans, Liver, Mice, Transgenic, Prediabetic State, Receptor, Insulin, Triglycerides, Glucose Clamp Technique, Mutagenesis, Site-Directed, Receptor, IGF Type 1, Muscle, Skeletal, Mice

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

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