Abstract:
The objective of this study was to investigate the effect of sacha inchi (Plukenetia volubilis L.) oil on hepatic damage, insulin sensitivity and glucose metabolizing enzymes in type 2 diabetes mellitus (T2DM) rats and identify its underlying mechanisms. T2DM rats were established by providing a high fat diet (HFD) and a low dose of streptozotocin (STZ). Diabetic rats were treated with sacha inchi oil at doses of 0.5, 1, and 2 ml/kg b.w., and a positive group was administrated with the antidiabetic drug, pioglitazone (30 mg/kg b.w.). The experiment was conducted over 5 weeks, during which time fasting blood glucose (FBG) and body weight were monitored. Also, hepatic histopathology, liver function tests, oxidative stress markers, and antioxidant enzymes were determined. Furthermore, proinflammatory cytokine mediators, the expression levels of proteins involved in insulin signaling and carbohydrate metabolic enzymes, and hepatic glycogen content were evaluated. Treatment with sacha inchi oil in a dose-dependent manner ameliorated FBG levels and tended to improve weight loss of diabetic rats. Sacha inchi oil also improved hepatic histopathological alterations in the diabetic rats, which correlates with the reduced serum levels of the liver enzymes ALT and AST. Additionally, sacha inchi oil significantly diminished the hepatic oxidative stress status of the diabetic rats by inhibiting MDA and enhancing the activities of antioxidant SOD, CAT and GPx. Proinflammatory cytokine TNF-α and IL-6 levels in the liver of the diabetic rats were significantly depleted by the sacha inchi. Moreover, sacha inchi oil treatment enhanced the hepatic insulin sensitivity of the diabetic rats, shown by increased IRS-1 and p-Akt protein expression, decreased PCK-1 and G6Pase protein expression, as well as an increment in hepatic glycogen content. In conclusion, the results suggest that sacha inchi oil exerts a potential hepatoprotective and hepatic insulin-sensitizing effects in the T2DM rat model, at least in part through the improvement in insulin signaling, glucose metabolizing enzymes, antioxidant defense and inhibiting proinflammatory cytokine production.