ArticleAging cell2012
Essential role of protein tyrosine phosphatase 1B in obesity-induced inflammation and peripheral insulin resistance during aging.
Article in Aging cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 88 citations in OpenAlex.
- A hypothalamus-liver-skeletal muscle axis controlled by JNK1 and FGF21 mediates olanzapine-induced insulin resistance in an intraperitoneal treatment in male mice.Redox biology · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Deletion of PTP1B in cardiomyocytes alters cardiac metabolic signaling to protect against cardiomyopathy induced by a high-fat diet.Science signaling · 2025Article
- Skeletal muscle mitochondrial dysfunction is associated with increased Gdf15 expression and circulating GDF15 levels in aged mice.Scientific reports · 2025Article
- Protein tyrosine phosphatase 1B in metabolic diseases and drug development.Nature reviews. Endocrinology · 2024Review
- The importance of including the C-terminal domain of PTP1BJournal of enzyme inhibition and medicinal chemistry · 2023Article
- Insulin Sensitivity Initially Worsens but Later Improves With Aging in Male C57BL/6N Mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- c-Jun N-terminal kinase signaling in cellular senescence.Archives of toxicology · 2023Review
- Role of Oxidative Stress on Insulin Resistance in Diet-Induced Obesity Mice.International journal of molecular sciences · 2023Article
- Computational Study of Asian Propolis Compounds as Potential Anti-Type 2 Diabetes Mellitus Agents by Using Inverse Virtual Screening with the DIA-DB Web Server, Tanimoto Similarity Analysis, and Molecular Dynamic Simulation.Molecules (Basel, Switzerland) · 2022Article
- Antidiabetic Activity of Ficusonolide, a Triterpene Lactone fromACS omega · 2021Article
- Redox regulation of the insulin signalling pathway.Redox biology · 2021Review
- Aging adipose: Depot location dictates age-associated expansion and dysfunction.Ageing research reviews · 2021Review
- Article
- Impact of global PTP1B deficiency on the gut barrier permeability during NASH in mice.Molecular metabolism · 2020Article
- Protein tyrosine phosphatase 1b deficiency protects against hepatic fibrosis by modulating nadph oxidases.Redox biology · 2019Article
- The leptin sensitizer celastrol reduces age-associated obesity and modulates behavioral rhythms.Aging cell · 2019Article
- Adiposity-Independent Effects of Aging on Insulin Sensitivity and Clearance in Mice and Humans.Obesity (Silver Spring, Md.) · 2019Article
- Programming of central and peripheral insulin resistance by low birthweight and postnatal catch-up growth in male mice.Diabetologia · 2018Article
- Protection against gamma-radiation injury by protein tyrosine phosphatase 1B.Redox biology · 2018Article
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes (T2DM). In this study, we have evaluated the role of PTP1B in the development of aging-associated obesity, inflammation, and peripheral insulin resistance by assessing metabolic parameters at 3 and 16 months in PTP1B(-/-) mice maintained on mixed genetic background (C57Bl/6J × 129Sv/J). Whereas fat mass and adipocyte size were increased in wild-type control mice at 16 months, these parameters did not change with aging in PTP1B(-/-) mice. Increased levels of pro-inflammatory cytokines, crown-like structures, and hypoxia-inducible factor (HIF)-1α were observed only in adipose tissue from 16-month-old wild-type mice. Similarly, islet hyperplasia and hyperinsulinemia were observed in wild-type mice with aging-associated obesity, but not in PTP1B(-/-) animals. Leanness in 16-month-old PTP1B(-/-) mice was associated with increased energy expenditure. Whole-body insulin sensitivity decreased in 16-month-old control mice; however, studies with the hyperinsulinemic-euglycemic clamp revealed that PTP1B deficiency prevented this obesity-related decreased peripheral insulin sensitivity. At a molecular level, PTP1B expression and enzymatic activity were up-regulated in liver and muscle of 16-month-old wild-type mice as were the activation of stress kinases and the expression of p53. Conversely, insulin receptor-mediated Akt/Foxo1 signaling was attenuated in these aged control mice. Collectively, these data implicate PTP1B in the development of inflammation and insulin resistance associated with obesity during aging and suggest that inhibition of this phosphatase by therapeutic strategies might protect against age-dependent T2DM.
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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.