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Molecular Nutrition
Abbreviations: DPPH, 2,2-diphenyl-1-picrylhydrazyl; GCK, glucokinase; G6Pase, glucose-6-phosphatase; LBEO, lemon balm essential oil; PEPCK, phosphoenolpyruvate carboxykinase; SREBP, sterol regulatory element-binding protein
Diabetes mellitus is a major public health problem that affects approximately 5 % of the world population(1). Type 2 diabetes is the most common form, accounting for more than 90 % of patients, and is characterised by chronic hyperglycaemia resulting from abnormalities in glucose metabolism and insulin secretion and activity.
Many recent studies on the treatment of type 2 diabetes have focused on the potential use of plant constituents with hypoglycaemic and hypolipidaemic effects. Consequently, there has been a growing interest in herbal essential oils, due to their antioxidative and hypolipidaemic activities(2-5). Several plant constituents have been implicated in insulin signalling pathways modulating glucose transport and glucose metabolism-related enzyme activation, and PPAR activation, all of which play roles in diabetes(6,7). In particular, glucokinase (GCK) gene transcription is stimulated by insulin and increased GCK activity enhances glucose utilisation and uptake in the liver. There have been efforts over recent years to discover and develop GCK activators as a novel therapy for type 2 diabetes(8). Glucose-6-phosphatase (G6Pase) is a key enzyme controlling hepatic gluconeogenesis and glucose output in liver(9,10) and is normally suppressed by insulin(11). Reduced activity of two key gluconeogenic enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and G6Pase, decreases hepatic glucose production(9,10).
In adipose and muscle tissues, insulin stimulates glucose uptake by rapidly recruiting GLUT4 from an intracellular compartment to the plasma membrane(12). PPAR control the expression of many genes involved in glucose and lipid metabolism. In a previous study, a single molecule was found to act as a dual agonist for both PPAR-α and PPAR-γ, producing simultaneous hypolipidaemic and hypoglycaemic effects, respectively(13). Sterol regulatory element-binding protein (SREBP)-1c is primarily involved in the regulation of fatty acid biosynthesis(14).
In addition to the gene expression changes in glucose metabolism and insulin signalling pathway, oxidative stress plays critical roles in insulin signalling and the aetiology...