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Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
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Long-Chain Acylcarnitines Decrease the Phosphorylation of the Insulin Receptor at Tyr1151 Through a PTP1B-Dependent
Karlis Vilks1,2, Melita Videja1,3, Marina Makrecka-Kuka1
1Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Aizkraukles Str. 21, LV-1006 Riga, Latvia.
International Journal of Molecular Sciences
|July 2, 2021
Summary
Long-chain acylcarnitines impair insulin signaling by activating PTP1B, reducing insulin receptor phosphorylation, and inhibiting Akt phosphorylation. This disrupts cellular energy metabolism and insulin sensitivity.
Area of Science:
- Metabolic pathways
- Cellular energy regulation
- Insulin resistance
Background:
- Lipid intermediates accumulation can disrupt energy metabolism.
- Elevated long-chain acylcarnitines are associated with insulin resistance.
Purpose of the Study:
- Investigate long-chain acylcarnitines' effects on insulin signaling.
- Elucidate mechanisms of impaired insulin response.
Main Methods:
- Examined palmitoylcarnitine's impact on insulin receptor (InsR) and Akt phosphorylation.
- Assessed protein tyrosine phosphatase 1B (PTP1B) activity.
- Utilized insulin-sensitizing agents and phosphatase inhibitors.
Main Results:
- Palmitoylcarnitine induced InsR dephosphorylation via PTP1B activation.
- Palmitoylcarnitine suppressed Akt phosphorylation independently of InsR status.
- Palmitoylcarnitine stimulated insulin release in RIN5F cells by inhibiting Akt phosphorylation.
Conclusions:
- Long-chain acylcarnitines activate PTP1B, decreasing InsR and Akt phosphorylation.
- This limits cellular response to insulin, contributing to insulin resistance.
- Palmitoylcarnitine's effects on Akt are independent of InsR phosphorylation levels.
Keywords:
Aktinsulin receptorinsulin resistancelong-chain acylcarnitinespalmitoylcarnitineprotein tyrosine phosphatase 1BMore Related Videos
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