An Extract of Urtica Dioica L. Mitigates Obesity Induced Insulin Resistance in Mice Skeletal Muscle Via Protein Phosphatase 2A (PP2A)
Affiliations
The leaf extract of Urtica dioica L. (UT) has been reported to improve glucose homeostasis in vivo, but definitive studies on efficacy and mechanism of action are lacking. We investigated the effects of UT on obesity- induced insulin resistance in skeletal muscle. Male C57BL/6J mice were divided into three groups: low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with UT. Body weight, body composition, plasma glucose and plasma insulin were monitored. Skeletal muscle (gastrocnemius) was analyzed for insulin sensitivity, ceramide accumulation and the post translational modification and activity of protein phosphatase 2A (PP2A). PP2A is activated by ceramides and dephosphorylates Akt. C2C12 myotubes exposed to excess free fatty acids with or without UT were also evaluated for insulin signaling and modulation of PP2A. The HFD induced insulin resistance, increased fasting plasma glucose, enhanced ceramide accumulation and PP2A activity in skeletal muscle. Supplementation with UT improved plasma glucose homeostasis and enhanced skeletal muscle insulin sensitivity without affecting body weight and body composition. In myotubes, UT attenuated the ability of FFAs to induce insulin resistance and PP2A hyperactivity without affecting ceramide accumulation and PP2A expression. UT decreased PP2A activity through posttranslational modification that was accompanied by a reduction in Akt dephosphorylation.
Liu D, Wang T, Zhao X, Chen J, Yang T, Shen Y J Cereb Blood Flow Metab. 2023; 44(6):985-999.
PMID: 38069840 PMC: 11318396. DOI: 10.1177/0271678X231219115.
Role of ceramides in diabetic foot ulcers (Review).
Wang Y, Sun Z, Zang G, Zhang L, Wang Z Int J Mol Med. 2023; 51(3).
PMID: 36799149 PMC: 9943538. DOI: 10.3892/ijmm.2023.5229.
Evidence-Based Anti-Diabetic Properties of Plant from the Occitan Valleys of the Piedmont Alps.
Boscaro V, Rivoira M, Sgorbini B, Bordano V, Dadone F, Gallicchio M Pharmaceutics. 2022; 14(11).
PMID: 36365189 PMC: 9693256. DOI: 10.3390/pharmaceutics14112371.
Anti-diabetic potential of Urtica Dioica: current knowledge and future direction.
Chehri A, Yarani R, Yousefi Z, Novin Bahador T, Shakouri S, Ostadrahimi A J Diabetes Metab Disord. 2022; 21(1):931-940.
PMID: 35673511 PMC: 9167344. DOI: 10.1007/s40200-021-00942-9.
Activation of Insulin Signaling by Botanical Products.
Rosenzweig T, Sampson S Int J Mol Sci. 2021; 22(8).
PMID: 33919569 PMC: 8073144. DOI: 10.3390/ijms22084193.