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

Abstract

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- 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.

Effect of Aqueous Leaf Extract of Terminalia catappa (Indian Almond) on the Liver of Alloxan-Induced Diabetic Wistar Rat

“…The levels of AST, ALT and ALP in this study significantly increased in diabetic induced Wistar rats, this was in line with the result of Ohaeri and Eluwa, [22]. Previous research has proven that a decrease in SOD and CAT activities within an hyperglycaemic state leads to an increase in ROS, which eventually contributes to oxidation-induced liver damage [23], thus, resulting in the leakage of AST, ALT and ALP from the liver cytosol into the blood stream, which gives an indication of the hepatotoxic effect of diabetogenic agent. Increase in serum activities of AST shows hepatic injuries similar to viral hepatitis, infarction, and muscle damages.…”

Evaluating the Potential of Plukenetia volubilis Linneo (Sacha Inchi) in Alleviating Cardiovascular Disease Risk Factors: A Mini Review

“…SI enhances hepatic insulin sensitivity by downregulating IR-β and stimulating IRS-1 and Akt. Moreover, SI also inhibited the activities of glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase-1 (PCK-1) in the liver of diabetic rats [98]. Reduced G-6-Pase and PCK-1 levels suppress hepatic gluconeogenesis and enhance glycogenesis, thereby reducing blood glucose levels [101].…”

“…The treatment of type 2 diabetic rats with 0.5-2 mL/kg of SI oil for five weeks significantly reduced fasting blood glucose levels and improved insulin sensitivity indices and glucose tolerance in a dose-dependent manner [98]. Insulin plays a pivotal role in regulating glucose metabolism by activating the insulin receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.…”

“…Reduced G-6-Pase and PCK-1 levels suppress hepatic gluconeogenesis and enhance glycogenesis, thereby reducing blood glucose levels [101]. The bioactive compounds present in SI, including ω-3 fatty acids, β-sitosterols, and flavonoids, contribute to its insulin sensitizing effect [98].…”

“…SI oil supplementation protected the liver from diabetesinduced liver damage, as evidenced by reduced serum alanine transaminase and aspartate transaminase (AST) levels, and improved hepatic histopathological changes [98]. The underlying mechanisms of such findings were attributed to the antioxidative and antiinflammatory effects of SI, as treatment with SI oil reduced the oxidative stress marker (MDA), enhanced the antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase) and reduced the inflammatory markers (TNF-α and IL-6) in the liver of diabetic rats [98]. However, to date, no studies have investigated how SI impacts other diabetes-related target organ damage, such as those affecting the kidneys, heart, and blood vessels.…”