Abstract
Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological and dietary interventions is used to prevent the progression of pre-diabetes to T2DM. However, poor patient compliance leads to negligence of the dietary intervention and thus reduced drug efficiency. Oleanolic acid (OA) has been reported to possess anti-diabetic effects in type 1 diabetic rats. However, the effects of this compound on pre-diabetes have not yet been established. Consequently, this study sought to evaluate the effects OA on a diet-induced pre-diabetes rat model. Pre-diabetic male Sprague Dawley rats were treated with OA in both the presence and absence of dietary intervention for a period of 12 weeks. The administration of OA with and without dietary intervention resulted in significantly improved glucose homeostasis through reduced caloric intake, body weights, plasma ghrelin concentration and glycated haemoglobin by comparison to the pre-diabetic control. These results suggest that OA may be used to manage pre-diabetes as it was able to restore glucose homeostasis and prevented the progression to overt type 2 diabetes.
Highlights
The global prevalence of type two diabetes mellitus (T2DM) has increased rapidly and has been implicated in the increased prevalence of metabolic syndrome [1,2]
A recent study in our laboratory showed that animals fed a high-fat high-carbohydrate (HFHC) diet for 20 weeks develop pre-diabetes and various metabolic derangements including increased HbA1c, impaired glucose tolerance and elevated levels of plasma ghrelin [8]
The administration of Oleanolic acid (OA) with and without dietary intervention resulted in a significant progressive decrease in caloric intake over the 12-week period by comparison to pre-diabetic control group (PC) (Table 1)
Summary
The global prevalence of type two diabetes mellitus (T2DM) has increased rapidly and has been implicated in the increased prevalence of metabolic syndrome [1,2]. The progression from normoglycemia to the diabetic state encompasses a long-lasting intermediate period of moderate hyperglycaemia and increased levels of glycated haemoglobin known as pre-diabetic state [4] These physiological derangements have been directly linked to the pathogenesis of T2DM [5]. OA and its derivatives have been reported to upregulate the expression of GLUT4 which increases the glucose uptake in adipose and muscle cell lines [14,15] Previous studies in our laboratory have indicated that the plant-derived triterpene oleanolic acid (OA) possesses anti-hyperglycaemic properties and suppress postprandial hyperglycaemia in a streptozotocin (STZ)-induced type 1 diabetic rat model [16,17]. The current study sought to evaluate the effects of administering plant-derived OA with and without diet intervention on glucose handling as well as the metabolic hormones involved in glucose homeostasis in a diet-induced pre-diabetes animal model
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