The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index.
Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction.
Open accessAbstract
The liver plays a central role in the control of glucose homeostasis and is subject to complex regulation by substrates, insulin, and other hormones. To investigate the effect of the loss of direct insulin action in liver, we have used the Cre-loxP system to inactivate the insulin receptor gene in hepatocytes. Liver-specific insulin receptor knockout (LIRKO) mice exhibit dramatic insulin resistance, severe glucose intolerance, and a failure of insulin to suppress hepatic glucose production and to regulate hepatic gene expression. These alterations are paralleled by marked hyperinsulinemia due to a combination of increased insulin secretion and decreased insulin clearance. With aging, the LIRKO liver exhibits morphological and functional changes, and the metabolic phenotype becomes less severe. Thus, insulin signaling in liver is critical in regulating glucose homeostasis and maintaining normal hepatic function.
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“For example, liver-specific insulin receptor knockout (LIRKO) mice develop insulin resistance, glucose intolerance, impaired insulin suppression of hepatic glucose production, and altered patterns of hepatic gene expression (208).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [208]
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Cites
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Self-citationAlternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene
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Self-citationADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism.Preprint
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Insulin signalling and the regulation of glucose and lipid metabolism
Saltiel, A. R., & Kahn, C. R. (2001) · Nature · doi:10.1038/414799a · Cited by 5,326
Self-citationMechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
Self-citationType 2 diabetes: principles of pathogenesis and therapy
Stumvoll, M., Goldstein, B. J., & van Haeften, T. W. (2005) · The Lancet · doi:10.1016/s0140-6736(05)61032-x · Cited by 2,662
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
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Self-citationRole of Bile Acids and Bile Acid Receptors in Metabolic Regulation
Lefebvre, P., Cariou, B., Lien, F., Kuipers, F., & Staels, B. (2009) · Physiological Reviews · doi:10.1152/physrev.00010.2008 · Cited by 1,678
Metadata
- Authors
- Michael, M. D., Kulkarni, R. N., Postic, C., Previs, S. F., Shulman, G. I., Magnuson, M. A., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Vanderbilt University (US)
- Yale University (US)
- Corresponding author
- Kahn, C.Ronald
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2000-07
- Volume
- 6
- Issue
- 1
- Pages
- 87-97
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2118688616
- Cited by
- 1,296
- References
- 82
- Citations by year
- 2026: 12 · 2025: 24 · 2024: 47 · 2023: 37 · 2022: 45 · 2021: 56 · 2020: 46 · 2019: 60 · 2018: 64 · 2017: 66 · 2016: 60 · 2015: 73 · 2014: 61 · 2013: 64 · 2012: 68
- FWCI
- 13.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- School of Medicine, Vanderbilt University
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK031036, P01DK042502, R01DK040936, F32DK009825)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- insulin resistance, insulin signaling, hepatocytes, insulin receptor, liver-specific knockout, glucose homeostasis, hepatic glucose production, hyperinsulinemia, insulin secretion, insulin clearance, hepatic gene expression, aging, liver dysfunction
- MeSH terms
- Aging, Animals, Glucose, Homeostasis, Insulin, Insulin Resistance, Liver, Mice, Inbred C57BL, Microscopy, Electron, Receptor, Insulin, Signal Transduction, Mice, Knockout, Mice
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