ArticleThe Journal of clinical investigation2000
Restored insulin-sensitivity in IRS-1-deficient mice treated by adenovirus-mediated gene therapy.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
- Combined Bioinformatic and Experimental Approaches to Analyze miR-182-3p and miR-24-3p Expression and Their Target Genes in Gestational Diabetes Mellitus and Iron Deficiency Anemia During Pregnancy.Current issues in molecular biology · 2025Article
- Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism.Nature communications · 2019Article
- Absence of IQGAP1 Protein Leads to Insulin Resistance.The Journal of biological chemistry · 2017Article
- Sequential cleavage of insulin receptor by calpain 2 and γ-secretase impairs insulin signalling.Diabetologia · 2016Article
- Application of network construction to estimate functional changes to insulin receptor substrates 1 and 2 in Huh7 cells following infection with the hepatitis C virus.Molecular medicine reports · 2016Article
- Compromised Wound Healing in Ischemic Type 2 Diabetic Rats.PloS one · 2016Article
- BMI-related progression of atypical PKC-dependent aberrations in insulin signaling through IRS-1, Akt, FoxO1 and PGC-1α in livers of obese and type 2 diabetic humans.Metabolism: clinical and experimental · 2015Article
- Administration of Danhong Injection to diabetic db/db mice inhibits the development of diabetic retinopathy and nephropathy.Scientific reports · 2015Article
- What model organisms and interactomics can reveal about the genetics of human obesity.Cellular and molecular life sciences : CMLS · 2012Review
- Atypical protein kinase C in cardiometabolic abnormalities.Current opinion in lipidology · 2012Review
- Peroxisome proliferator-activated receptor γ decouples fatty acid uptake from lipid inhibition of insulin signaling in skeletal muscle.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Article
- Correction of metabolic abnormalities in a rodent model of obesity, metabolic syndrome, and type 2 diabetes mellitus by inhibitors of hepatic protein kinase C-ι.Metabolism: clinical and experimental · 2012Article
- Inhibition of insulin signaling in endothelial cells by protein kinase C-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase (PI3K).The Journal of biological chemistry · 2012Article
- Insulin signaling and insulin sensitizing in muscle and liver of obese monkeys: peroxisome proliferator-activated receptor gamma agonist improves defective activation of atypical protein kinase C.Antioxidants & redox signaling · 2011Article
- Spontaneous Irs1 passenger mutation linked to a gene-targeted SerpinB2 allele.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Metabolic functions of atypical protein kinase C: "good" and "bad" as defined by nutritional status.American journal of physiology. Endocrinology and metabolism · 2010Review
- The transcription factor ATF4 regulates glucose metabolism in mice through its expression in osteoblasts.The Journal of clinical investigation · 2009Article
- Article
- The critical role of atypical protein kinase C in activating hepatic SREBP-1c and NFkappaB in obesity.Journal of lipid research · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin resistance is commonly observed both in overt diabetes and in individuals prone to, but not yet manifesting, diabetes. Hence the maintenance or restoration of insulin sensitivity may prevent the onset of this disease. We previously showed that homozygous disruption of insulin receptor substrate-1 (IRS-1) in mice resulted in insulin resistance but not diabetes. Here, we have explored the mechanism of systemic insulin resistance in these mice and used adenovirus-mediated gene therapy to restore their insulin sensitivity. Mice expressing the IRS-1transgene showed almost normal insulin sensitivity. Expression of an IRS-1 mutant (IRS-1Deltap85) lacking the binding site for the p85 subunit of phosphatidylinositol 3-kinase (PI3K) also restored insulin sensitivity, although PI3K is known to play a crucial role in insulin's metabolic responses. Protein kinase B (PKB) activity in liver was decreased in null mice compared with the wild-type and the null mice expressing IRS-1 or IRS-1Deltap85. In primary hepatocytes isolated from null mice, expression of IRS-1 enhanced both PI3K and PKB activities, but expression of IRS-1Deltap85 enhanced only PKB. These data suggest that PKB in liver plays a pivotal role in systemic glucose homeostasis and that PKB activation might be sufficient for reducing insulin resistance even without full activation of PI3K.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.