ArticleNature communications2016
Differential hepatic distribution of insulin receptor substrates causes selective insulin resistance in diabetes and obesity.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 128 citations in OpenAlex.
- Insulin resistance in the 21st century: new takes on an old problem-2025 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetologia · 2026Review
- Single-cell and spatial omics in liver identify cell-cell communication regulators in aging and insulin resistance.Metabolism: clinical and experimental · 2026Article
- Revisiting Insulin Resistance in the Pathophysiology of Type 2 Diabetes Mellitus: A Multi-Organ Perspective.Diabetes & metabolism journal · 2026Review
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- Therapeutic delivery of albumin-binding siRNA targeting IRS2 to diverse cell types reduces mammary tumor growth.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Type 2 diabetes mellitus.Nature reviews. Disease primers · 2026Review
- MASLD In Children - A Distinct Phenotype?Current obesity reports · 2026Review
- A Combined Probiotic-International journal of molecular sciences · 2026Article
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- Improving Non-alcoholic Fatty Liver Disease Treatment in High-fat Diet Fed Mice with Fisetin and Hydroxychloroquine: The Cooperative Pathways for Improved Metabolic Health.Current medicinal chemistry · 2026Article
- Advances in the application of insulin resistance-related indicators in the clinical evaluation of metabolic dysfunction-associated steatotic liver disease.Frontiers in gastroenterology (Lausanne, Switzerland) · 2026Review
- Fructose and follistatin potentiate acute MASLD during complete hepatic insulin resistance.Nature communications · 2025Article
- Hepatic Insulin Resistance and Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: New Insights into Mechanisms and Clinical Implications.Diabetes & metabolism journal · 2025Review
- Spatial regulation of glucose and lipid metabolism by hepatic insulin signaling.Cell metabolism · 2025Article
- MASLD in children: integrating epidemiological trends with mechanistic and translational advances.The Journal of clinical investigation · 2025Review
- Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunctionassociated steatotic liver disease.Clinical and molecular hepatology · 2025Review
- Lipogenesis and MASLD: re-thinking the role of SREBPs.Archives of toxicology · 2025Review
- Whole Exome Sequencing in 26 Saudi Patients Expands the Mutational and Clinical Spectrum of Diabetic Nephropathy.Medicina (Kaunas, Lithuania) · 2025Article
- Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatic insulin signalling involves insulin receptor substrates (Irs) 1/2, and is normally associated with the inhibition of gluconeogenesis and activation of lipogenesis. In diabetes and obesity, insulin no longer suppresses hepatic gluconeogenesis, while continuing to activate lipogenesis, a state referred to as 'selective insulin resistance'. Here, we show that 'selective insulin resistance' is caused by the differential expression of Irs1 and Irs2 in different zones of the liver. We demonstrate that hepatic Irs2-knockout mice develop 'selective insulin resistance', whereas mice lacking in Irs1, or both Irs1 and Irs2, develop 'total insulin resistance'. In obese diabetic mice, Irs1/2-mediated insulin signalling is impaired in the periportal zone, which is the primary site of gluconeogenesis, but enhanced in the perivenous zone, which is the primary site of lipogenesis. While hyperinsulinaemia reduces Irs2 expression in both the periportal and perivenous zones, Irs1 expression, which is predominantly in the perivenous zone, remains mostly unaffected. These data suggest that 'selective insulin resistance' is induced by the differential distribution, and alterations of hepatic Irs1 and Irs2 expression.
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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.