PTP1B inhibitor improves both insulin resistance and lipid abnormalities in vivo and in vitro
Abstract
PTP1B is a negative regulator of insulin signaling pathway. This study investigated the effects of compound CCF06240, a PTP1B inhibitor, on insulin sensitivity and lipid metabolic abnormalities in vivo and in vitro, respectively. The insulin resistant IRM mouse model was induced by HFD. The responses to insulin were determined by OGTT, ITT, and hyperinsulinemic-euglycemic clamp test. The body weight and the levels of serum TC and TG were measured to estimate the lipid metabolism in vivo. Recombinant human GST-PTP1B protein was used to measure the inhibition of CCF06240 on PTP1B activity. The hepatocyte lipid accumulation was induced by high concentrations of FFA and insulin in HepG(2) cells, and evaluated by the Oil Red O method. In IRM mice, the insulin resistance was improved; the body weight and the levels of TC and TG were also reduced by oral CCF06240 administration. In lipid accumulated model cells, CCF06240 was found to reverse the increased PTP1B activity, enhance the insulin-induced tyrosine phosphorylation in insulin signaling pathway, attenuate the FFA-insulin-induced cellular lipid accumulation, and down-regulate the expressions of genes related fatty acid synthesis. These results demonstrated that the PTP1B inhibitor, compound CCF06240, could increase insulin sensitivity through the regulation of insulin signaling pathway, and decrease FFA-insulin-induced hepatocytes lipid accumulation by reducing fatty acid syntheses.
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Current treatment algorithms are less prescriptive than before and advocate a more personalized approach to the choice of medications and treatment targets for type 2 diabetes.
“While current treatment algorithms are less prescriptive than before and advocate a more personalized approach to the choice of medications and treatment targets for type 2 diabetes131”
From Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future (2014) · cites this paper as [131]
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Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future
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- Authors
- Ma, Y.-M., Tao, R.-Y., Liu, Q., Li, J., Tian, J.-Y., Zhang, X.-L., Xiao, Z.-Y., & Ye, F.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Ye, Fei
- Venue
- Molecular and Cellular Biochemistry
- Published
- 2011-05-21
- Volume
- 357
- Issue
- 1-2
- Pages
- 65-72
- ISSN
- 0300-8177 (ISSN-L)
- 1573-4919
- OpenAlex
- W2033715247
- Cited by
- 62
- References
- 24
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 1 · 2016: 4 · 2015: 4 · 2014: 8 · 2013: 5 · 2012: 5
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular and Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- PTP1B, PTP1B inhibitors, insulin resistance, insulin signaling pathway, lipid metabolism, hepatic lipid accumulation, fatty acid synthesis, high-fat diet, tyrosine phosphorylation
- MeSH terms
- Animals, Benzofurans, Blood Glucose, Body Weight, Fatty Acids, Glucose Tolerance Test, Humans, Insulin Resistance, Phenylpropionates, Glucose Clamp Technique, Signal Transduction, Hepatocytes, Lipogenesis, Lipid Metabolism, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 1
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