Berberine treatment attenuates the palmitate-mediated inhibition of glucose uptake and consumption through increased 1,2,3-triacyl-sn-glycerol synthesis and accumulation in H9c2 cardiomyocytes

In cardiomyocytes insulin binding to its receptor stimulates glucose uptake through the insulin signaling cascade. Palmitate is taken up by cardiomyocytes and converted to palmitoyl-CoA. The palmitoyl-CoA may be used for ATP production through oxidative phosphorylation (OX-PHOS) or combined with glycerol-3-phosphate (G3P) to form lysophosphatidic acid (LPA) followed by phosphatidic acid (PA). PA is converted to 1,2-diacyl-sn-glycerol (DAG) and then to 1,2,3-triacyl-sn-glycerol (TAG) by 1,2-diacyl-sn-glycerol acyltransferase-2 (DGAT-2). Excess palmitate results in increased DAG production which activates protein kinase C (PKC) which in turn inhibits the insulin signaling cascade. Berberine stimulates glucose uptake through adenosine monophosphate kinase (AMPK) activation of protein kinase B (AKT) and through attenuation of the DAG mediated inhibition of glucose uptake by reducing cellular DAG levels via increasing DGAT-2 expression/activity and reducing TAG hydrolysis.134