Sutherlandia frutescens prevents changes in diabetes-related gene expression in a fructose-induced insulin resistant cell model

Ethnopharmacological relevance: The African medicinal plant Sutherlandia frutescens (L.) R.Br. (Fabaceae) is traditionally used to treat diabetes and has been shown to have anti-diabetic properties in animal models. The present study investigated the capacity of an aqueous extract of Sutherlandia frutescens to prevent insulin resistance (a precursor of type 2 diabetes) in a human liver cell culture and to identify genes regulated by Sutherlandia frutescens treatment. Materials and methods: A combination of insulin and fructose was used to generate an in vitro model of insulin resistance in human liver cells to compare untreated control, insulin resistant and Sutherlandia frutescens treated insulin resistant cultures. Insulin resistance and its prevention by Sutherlandia frutescens were measured by glucose uptake, gluconeogenesis and lipid accumulation in the cell cultures. Changes in gene expression were quantified using the RT(2)Profiler (TM) PCR Array of 84 diabetes-related genes. Results: The insulin resistant Chang liver cells took up significantly less 2-[H-3]-deoxyglucose (p < 0.05) than controls, released more glucose into the culture medium (p < 0.05) and accumulated more intracellular lipid (p < 0.05). Simultaneous treatment with Sutherlandia frutescens prevented development of these insulin resistance parameters (p < 0.05). A total of 27 potential gene targets of Sutherlandia frutescens were significantly up or down regulated in the Sutherlandia frutescens treated insulin resistant cells. The gene VAMP3, which plays a role in vesicle transport, was down-regulated by insulin resistance, and up-regulated by Sutherlandia frutescens. Twenty six other genes encoding vesicle transporters, receptors, signalling molecules, transcription factors, and metabolic enzymes were significantly regulated by Sutherlandia frutescens. Conclusion: These results confirm that Sutherlandia frutescens can prevent insulin resistance in hepatocytes. The identified changes in gene expression indicate several potential mechanisms of anti-diabetic action for Sutherlandia frutescens, reflecting the multiple bioactive compounds previously identified in aqueous extracts of Sutherlandia frutescens. (C) 2013 Elsevier Ireland Ltd. All rights reserved.