ArticleMolecular and cellular biology2009
The Irs1 branch of the insulin signaling cascade plays a dominant role in hepatic nutrient homeostasis.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.
- Pooled it
- Progranulin deficiency in the brain activates an insulin signaling pathway that may promote neurodegeneration.iScience · 2026Article
- Fructose and follistatin potentiate acute MASLD during complete hepatic insulin resistance.Nature communications · 2025Article
- Relationship of Ageing to Insulin Resistance and Atherosclerosis.Metabolites · 2025Review
- Blood glucose reduction associated with wholewheat noodle diet in rats with type 2 diabetes mellitus.Scientific reports · 2025Article
- Comparison of different insulin resistance surrogates in predicting hyperuricemia in non-diabetic Yi residents in Yunnan Province.Frontiers in endocrinology · 2025Article
- IFNγ-IL12 axis regulates intercellular crosstalk in metabolic dysfunction-associated steatotic liver disease.Nature communications · 2024Article
- Loss of FoxO1 activates an alternate mechanism of mitochondrial quality control for healthy adipose browning.Clinical science (London, England : 1979) · 2024Article
- BRD7 improves glucose homeostasis independent of IRS proteins.The Journal of endocrinology · 2023Article
- Reciprocal Regulation of Hepatic TGF-β1 and Foxo1 Controls Gluconeogenesis and Energy Expenditure.Diabetes · 2023Article
- Cinnamaldehyde supplementation acts as an insulin mimetic compound improving glucose metabolism during adolescence, but not during adulthood, in healthy male rats.Hormones (Athens, Greece) · 2023Article
- The Pathogenesis of Diabetes.International journal of molecular sciences · 2023Review
- Coronarin A modulated hepatic glycogen synthesis and gluconeogenesis via inhibiting mTORC1/S6K1 signaling and ameliorated glucose homeostasis of diabetic mice.Acta pharmacologica Sinica · 2023Article
- Review
- Distinct impacts of fat and fructose on the liver, muscle, and adipose tissue metabolome: An integrated view.Frontiers in endocrinology · 2022Article
- Cross-Talking Pathways of Forkhead Box O1 (FOXO1) Are Involved in the Pathogenesis of Alzheimer's Disease and Huntington's Disease.Oxidative medicine and cellular longevity · 2022Article
- Insulin action at a molecular level - 100 years of progress.Molecular metabolism · 2021Review
- The transcriptional coregulator CITED2 suppresses expression of IRS-2 and impairs insulin signaling in endothelial cells.American journal of physiology. Endocrinology and metabolism · 2021Article
- FoxO1 suppresses Fgf21 during hepatic insulin resistance to impair peripheral glucose utilization and acute cold tolerance.Cell reports · 2021Article
- Heme Oxygenase-1 Regulates Ferrous Iron and Foxo1 in Control of Hepatic Gluconeogenesis.Diabetes · 2021Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
We used a Cre-loxP approach to generate mice with varied expression of hepatic Irs1 and Irs2 to establish the contribution of each protein to hepatic nutrient homeostasis. While nutrient-sensitive transcripts were expressed nearly normally in liver lacking Irs2 (LKO2 mice), these transcripts were significantly dysregulated in liver lacking Irs1 (LKO1 mice) or Irs1 and Irs2 together (DKO mice). Similarly, a set of key gluconeogenic and lipogenic genes was regulated nearly normally by feeding in liver retaining a single Irs1 allele without Irs2 (DKO/1 mice) but was poorly regulated in liver retaining one Irs2 allele without Irs1 (DKO/2 mice). DKO/2 mice, but not DKO/1 mice, also showed impaired glucose tolerance and insulin sensitivity-though both Irs1 and Irs2 were required to suppress hepatic glucose production during hyperinsulinemic-euglycemic clamp. In contrast, either hepatic Irs1 or Irs2 mediated suppression of HGP by intracerebroventricular insulin infusion. After 12 weeks on a high-fat diet, postprandial tyrosine phosphorylation of Irs1 increased in livers of control and LKO2 mice, whereas tyrosine phosphorylation of Irs2 decreased in control and LKO1 mice. Moreover, LKO1 mice -- but not LKO2 mice -- that were fed a high-fat diet developed postprandial hyperglycemia. We conclude that Irs1 is the principal mediator of hepatic insulin action that maintains glucose homeostasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.