Sacha Inchi (Plukenetia volubilis L.) Oil Improves Hepatic Insulin Sensitivity and Glucose Metabolism through Insulin Signaling Pathway in a Rat Model of Type 2 Diabetes

This study aimed to evaluate the role of sacha inchi oil (SI) in alleviating hepatic insulin resistance and improving glucose metabolism by inhibiting oxidative stress and inflammation in a rat model of type 2 diabetes. This model was established by providing a high-fat diet and streptozotocin to the rats, thereby inducing diabetes. The diabetic rats were treated orally with 0.5, 1, and 2 mL/kg body weight (b.w.) of SI or 30 mg/kg b.w. of pioglitazone daily for 5 weeks. Blood and hepatic tissues were used for insulin sensitivity, carbohydrate metabolism, oxidative stress, and inflammatory status assessment. Treatment with SI attenuated hyperglycemia and insulin resistance indices, and improved hepatic histopathological alterations in the diabetic rats in a dose-dependent manner, which is correlated with the decreased serum levels of the liver enzymes, alanine transaminase and aspartate transaminase. SI significantly diminished the hepatic oxidative status of the diabetic rats by inhibiting malondialdehyde and enhancing the antioxidant superoxide dismutase, catalase, and glutathione peroxidase activities. Moreover, pro-inflammatory cytokine levels, including tumor necrosis factor-α and interleukin-6, in the liver of the diabetic rats were significantly decreased by the SI. Furthermore, SI treatment enhanced the hepatic insulin sensitivity of the diabetic rats, as shown by the increased insulin receptor substrate-1 and p-Akt protein expression, decreased phosphoenolpyruvate carboxykinase-1 and glucose-6-phospatase protein expression, and increased hepatic glycogen content. Overall, these findings suggest that SI exerts a potential hepatic insulin-sensitizing effect and an improvement in glucose metabolism in the type 2 diabetic rats, at least in part through enhancing insulin signaling, antioxidant defense, and inhibiting inflammation.