Diabetes is reaching pandemic levels in both developing and developed countries and requires safe, affordable, and effective therapies. This report summarises work in our laboratory on the effects of Zingiber officinale (ginger) and its components in diabetes models and provides a future outlook on the potential for their use in type 2 diabetes. A high fat diet rat model showed modulation of body weight gain and normalisation of glucose and lipid metabolic disturbances, with reduction of insulin resistance in a high fat-high carbohydrate diet model. Ginger extract inhibits enhanced NF-κB in liver of high fat-fed rats through inhibition of the IKK/IκBα/NF-κB classical pathway. The major active component (S)-[6]-gingerol inhibited elevated cytokines in inflamed HuH7 cells through suppression of COX2 expression and protection against the ROS pathway. Ginger extract and gingerols enhanced glucose uptake in L6 myotubes, by enhancing translocation of GLUT4 to the surface membrane and activation of AMPKα1 through a Ca2+/calmodulin-dependent protein kinase kinase pathway. (S)-[6]-Gingerol also enhanced energy metabolism through marked increment of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) gene expression and mitochondrial content in L6 skeletal muscle cells. Future studies will require well designed clinical trials on ginger preparations of defined chemical composition. 1. Introduction 1.1. Diabetes and Prediabetic States: The Scope of the Problem According to recent estimates the prevalence of diabetes has reached pandemic proportions, with 382 million people worldwide living with this condition. A further 316 million (6.9%) adults worldwide with impaired glucose tolerance are at high risk of developing diabetes [1]. By the end of 2013 it was estimated that there would be 5.1 million deaths and a cost of USD 548 million in health care spending. Estimates indicate that there will be 592 million people living with the disease within 25 years without positive action, yet it is considered that most of these cases are preventable [1]. Contrary to expectations, 80% of people with diabetes live in low- and middle-income countries [1]. There is also a growing trend for younger people to develop diabetes, leading to an increasing incidence of premature deaths [2]. Diabetes mellitus is characterised by chronic hyperglycemia resulting from impaired insulin action/secretion [3]. Type 2 diabetes, accounting for >90% of diabetes [3], is associated with metabolic disorders of both lipid and carbohydrate [4]. Effective control of hyperglycemia in
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