Preventative effect of Zingiber officinale on insulin resistance in a high-fat high-carbohydrate diet-fed rat model and its mechanism of action.

Insulin resistance is a core component of metabolic syndrome and usually precedes the development of type 2 diabetes mellitus. We have examined the preventative effect of an ethanol extract of ginger (Zingiber officinale, Zingiberaceae) on insulin resistance in a high-fat high-carbohydrate (HFHC) diet-fed rat model of metabolic syndrome. The HFHC control rats displayed severe insulin resistance, whilst rats treated with ginger extract (200 mg/kg) during HFHC diet feeding showed a significant improvement of insulin sensitivity using the homeostatic model assessment of insulin resistance (HOMA-IR) after 10 weeks (p < 0.01). An in vitro mechanistic study showed that (S)-[6]-gingerol, the major pungent phenolic principle in ginger, dose-dependently (from 50 to 150 μM) increased AMPK α-subunit phosphorylation in L6 skeletal muscle cells. This was accompanied by a time-dependent marked increment of PGC-1α mRNA expression and mitochondrial content in L6 skeletal muscle cells. These results suggest that the protection from HFHC diet-induced insulin resistance by ginger is likely associated with the increased capacity of energy metabolism by its major active component (S)-[6]-gingerol.