AD01, an Antidiabetic Plant of the Eastern James Bay Cree, Attenuates Insulin Resistance in a Diet-Induced Obesity Mouse Model

We investigated the anti-diabetic effect of a medicinal plant used by the Cree nation of northern Quebec, AD01, in a diet-induced obesity (DIO) mouse model. C57BL6 mice were divided into 5 groups and given a standard CHOW diet (˜ 4% of lipids) or a high fat-diet (˜ 35% of lipids) during 8 weeks until they became obese and insulin resistant. Treatment then began by adding the plant extract at 3 different doses (125, 250, 500mg/kg) into the high fat diet for another 8 weeks. At the end of the study, insulin sensitive tissues (liver, skeletal muscle, adipose tissue) were collected to investigate the plant's molecular mechanisms. AD01 prevented weight gain (by 6%), reduced blood glucose (by 13%) and plasma insulin (by 65%) while preventing hepatic steatosis (up to 42% reduction in hepatic triglyceride levels) in DIO mice. Western immunoblot analysis demonstrated that AD01 stimulated the activation of insulin dependent AKT pathway and increased the expression of Glut 4 in skeletal muscle. In the liver, AD01 stimulated two pathways; the insulin dependent Akt and the insulin independent AMPK ones. The improvement of hepatic steatosis observed in DIO treated mice was associated with a reduction of inflammation and with a decrease in the hepatic content of SREBP-1. These data suggest that AD01 exerts potential anti-diabetic action by improving insulin sensitivity and mitigating high-fat diet-induced obesity and hyperglycemia. They also validate the safety and efficacy of this plant. AD01 thus represents a promising candidate for culturally relevant complementary treatment in Cree diabetics.