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Updated: May 18, 2026

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
Isoorientin reverts TNF-α-induced insulin resistance in adipocytes activating the insulin signaling pathway
Angel Josabad Alonso-Castro1, Rocio Zapata-Bustos, Guadalupe Gómez-Espinoza
1Instituto Potosino de Investigación Científica y Tecnológica, Molecular Biology Division, San Luis Potosí, México.
Abstract:
Isoorientin (ISO) is a plant C-glycosylflavonoid with purported antidiabetic effects but unexplored mechanisms of action. To gain insight into its antidiabetic mechanisms, we assayed nontoxic ISO concentrations on the 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxy-d-glucose (2-NBDG) uptake by murine 3T3-F442A and human sc adipocytes. In insulin-sensitive adipocytes, ISO stimulated the 2-NBDG uptake by 210% (murine) and 67% (human), compared with insulin treatment. Notably, ISO also induced 2-NBDG uptake in murine (139%) and human (60%) adipocytes made resistant to insulin by treatment with TNF-α, compared with the incorporation induced in these cells by rosiglitazone. ISO induction of glucose uptake in adipocytes was abolished by inhibitors of the insulin signaling pathway. These inhibitors also blocked the proper phosphorylation of insulin signaling pathway components induced by ISO in both insulin-sensitive and insulin-resistant adipocytes. Additionally, ISO stimulated the transcription of genes encoding components of insulin signaling pathway in murine insulin-sensitive and insulin-resistant adipocytes. In summary, we show here that ISO exerts its antidiabetic effects by activating the insulin signaling pathway in adipocytes, reverts the insulin resistance caused in these cells by TNF-α by stimulating the proper phosphorylation of proteins in this signaling pathway, and induces the expression of genes encoding these proteins.
Insights
Isoorientin (ISO) activates the insulin signaling pathway in fat cells, enhancing glucose uptake. This plant flavonoid also reverses insulin resistance induced by TNF-α, offering potential antidiabetic benefits.
Area of Science:
- Biochemistry
- Metabolic Research
- Pharmacology
Background:
- Isoorientin (ISO), a plant C-glycosylflavonoid, is suggested to possess antidiabetic properties.
- The precise mechanisms underlying ISO's potential antidiabetic effects remain largely unelucidated.
Purpose of the Study:
- To investigate the antidiabetic mechanisms of Isoorientin (ISO) in adipocytes.
- To determine if ISO influences glucose uptake and insulin signaling pathways.
Main Methods:
- Assessed 2-NBDG uptake in murine 3T3-F442A and human adipocytes treated with ISO.
- Evaluated ISO's effects on insulin signaling pathway components and gene expression.
- Utilized TNF-α to induce insulin resistance in adipocytes for comparative analysis.
Main Results:
- ISO significantly stimulated glucose uptake in both insulin-sensitive and insulin-resistant adipocytes.
- ISO's glucose uptake induction was dependent on the insulin signaling pathway.
- ISO treatment promoted proper phosphorylation of insulin signaling proteins and stimulated relevant gene transcription.
Conclusions:
- Isoorientin (ISO) exerts antidiabetic effects by activating the insulin signaling pathway in adipocytes.
- ISO effectively reverses TNF-α-induced insulin resistance by modulating key signaling proteins and gene expression.
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