RESUMEN
Several reports indicate anti-hyperglycemic effects of Syzygium aromaticum. In the present study, we report for the first time that clove extract (SAM) and its compound nigricin (NGC) decreases free fatty acid-mediated insulin resistance in mouse myoblasts. In addition, NGC was able to diminish insulin resistance in a diabetic mouse model. We observed that SAM and its compound NGC exhibited significant antioxidant activity in murine skeletal muscle cells. They also modulated stress signaling by reducing p38 MAP kinase phosphorylation. NGC and SAM treatments enhanced proximal insulin signaling by decreasing serine phosphorylation of insulin receptor substrate-1 (IRS-1) and increasing its tyrosine phosphorylation. SAM and NGC treatments also modified distal insulin signaling by enhancing protein kinase B (PKB) and glycogen synthase kinase-3-beta (GSK-3 beta) phosphorylation in muscle cells. Glucose uptake was enhanced in muscle cells after treatment with SAM and NGC. We observed increased glucose tolerance, glucose-stimulated insulin secretion, decreased insulin resistance, and increased beta cell function in diabetic mice treated with NGC. The results of our study demonstrate that clove extract and its active agent NGC can be potential therapeutic agents for alleviating insulin resistance.
Asunto(s)
Ácidos Grasos no Esterificados/farmacología , Resistencia a la Insulina , Fibras Musculares Esqueléticas/efectos de los fármacos , Syzygium/química , Animales , Benzodioxoles/farmacología , Cromatografía Liquida , Diabetes Mellitus Experimental/tratamiento farmacológico , Femenino , Flores/química , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Glucógeno Sintasa Quinasa 3/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Células Secretoras de Insulina/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Fibras Musculares Esqueléticas/metabolismo , Mioblastos Esqueléticos/efectos de los fármacos , Mioblastos Esqueléticos/metabolismo , Fosforilación , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Tirosina/químicaRESUMEN
The present study aimed to decipher the mechanism of action of selected anti-diabetic plants extracts on palmitic acid mediated insulin resistance in muscle cells. Our results showed that extract from Peganum harmala seeds, Eucalyptus camaldulensis and Syzygium aromaticum leaves, showed significant antioxidant activity. We found that these extracts were able to affect stress signalling by reducing p-38 MAP kinase phosphorylation. They also reduced phosphorylation of substrate for insulin receptor (IRS) at serine residues and increased its phosphorylation at tyrosine residues and also enhanced PKB phosphorylation. Glucose uptake was also enhanced in muscle cells after treatment with these extracts. Extracts from Lantana camara, Psidium gujava fruit and different parts of Cassia alata did not affect FFA mediated down-regulation of insulin signalling. The study conclude that seeds of Peganum harmala and leaves of Eucalyptus camaldulensis and Syzygium aromaticum enhanced insulin signal transduction and glucose uptake in muscle cells via reducing oxidative stress. As a result, these herbal extracts may be considered useful to protect from insulin resistance.