ArticleEndocrinology2009
Inhibition of protein tyrosine phosphatase-1B with antisense oligonucleotides improves insulin sensitivity and increases adiponectin concentrations in monkeys.
Article in Endocrinology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 71 citations in OpenAlex.
- The role of classical protein tyrosine phosphatases in diabetic kidney disease and therapeutic implications.Journal of biomedical science · 2026Review
- Protein Tyrosine Phosphatase 1B (PTP1B): A Comprehensive Review of Its Role in Pathogenesis of Human Diseases.International journal of molecular sciences · 2024Review
- Protein tyrosine phosphatase 1B in metabolic diseases and drug development.Nature reviews. Endocrinology · 2024Review
- Protein tyrosine phosphatase 1B in metabolic and cardiovascular diseases: from mechanisms to therapeutics.Frontiers in cardiovascular medicine · 2024Review
- The PTP1B inhibitor MSI-1436 ameliorates liver insulin sensitivity by modulating autophagy, ER stress and systemic inflammation in Equine metabolic syndrome affected horses.Frontiers in endocrinology · 2023Article
- Article
- Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives.International journal of molecular sciences · 2022Review
- The Influence of Diet on Metabolism and Health Across the Lifespan in Nonhuman Primates.Current opinion in endocrine and metabolic research · 2022Article
- Recent advances in PTP1B signaling in metabolism and cancer.Bioscience reports · 2021Review
- MSI-1436 improves EMS adipose derived progenitor stem cells in the course of adipogenic differentiation through modulation of ER stress, apoptosis, and oxidative stress.Stem cell research & therapy · 2021Article
- The Role of Protein Tyrosine Phosphatase (PTP)-1B in Cardiovascular Disease and Its Interplay with Insulin Resistance.Biomolecules · 2019Review
- Animal models of obesity and diabetes mellitus.Nature reviews. Endocrinology · 2018Review
- Novel Mixed-Type Inhibitors of Protein Tyrosine Phosphatase 1B. Kinetic and Computational Studies.Molecules (Basel, Switzerland) · 2017Article
- Use and Importance of Nonhuman Primates in Metabolic Disease Research: Current State of the Field.ILAR journal · 2017Review
- Postprandial hyperglycemia and postprandial hypertriglyceridemia in type 2 diabetes.Journal of biomedical research · 2017Article
- Targeting hepatic glucose metabolism in the treatment of type 2 diabetes.Nature reviews. Drug discovery · 2016Review
- Effects of hepatic protein tyrosine phosphatase 1B and methionine restriction on hepatic and whole-body glucose and lipid metabolism in mice.Metabolism: clinical and experimental · 2015Article
- Protein-tyrosine phosphatase 1B substrates and metabolic regulation.Seminars in cell & developmental biology · 2015Review
- Liraglutide Exerts Antidiabetic Effect via PTP1B and PI3K/Akt2 Signaling Pathway in Skeletal Muscle of KKAy Mice.International journal of endocrinology · 2014Article
- High-fat diet-induced changes in liver thioredoxin and thioredoxin reductase as a novel feature of insulin resistance.FEBS open bio · 2014Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Protein tyrosine phosphatase (PTP)-1B antagonizes insulin signaling and is a potential therapeutic target for insulin resistance associated with obesity and type 2 diabetes. To date, studies of PTP-1B have been limited by the availability of specific antagonists; however, treatment of rodents with antisense oligonucleotides (ASOs) directed against PTP-1B improves insulin sensitivity, inhibits lipogenic gene expression, and reduces triglyceride accumulation in liver and adipose tissue. Here we investigated ASO-mediated PTP-1B inhibition in primates. First, PTP-1B ASO (ISIS 113715) dose-dependently inhibited PTP-1B mRNA and protein expression in cultured monkey hepatocytes. Subcutaneous administration of ISIS 113715 reduced PTP-1B mRNA expression in liver and adipose tissue of normal-weight monkeys by 40-50% and improved insulin sensitivity during an iv glucose tolerance test (IVGTT). In obese, insulin-resistant rhesus monkeys, treatment with 20 mg/kg ISIS 113715 for 4 wk reduced fasting concentrations of insulin and glucose and reduced insulin responses during an IVGTT. In these animals, adiponectin concentrations were also increased by 70%, most of which was an increase of high-molecular-weight oligomers. These effects were not observed in monkeys on a lower, dose-escalation regimen (1-10 mg/kg over 9 wk). Overall, the increase of adiponectin concentrations during ISIS 113715 treatment was correlated with the lowering of insulin responses during IVGTT (r = -0.47, P = 0.042). These results indicate that inhibition of PTP-1B with ASOs such as ISIS 113715 may be a viable approach for the treatment and prevention of obesity-associated insulin resistance and type 2 diabetes because they potently increase adiponectin concentrations in addition to improving insulin sensitivity.
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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.