Abstract
Because diabetes mellitus (DM) is a multifactorial metabolic disease, its prevention and treatment has been a constant challenge for basic and clinical investigators focused on translating their discoveries into clinical treatment of this complex disorder. In this review, we highlight recent experimental and clinical evidences of potential coadjuvants in the management of DM, such as polyphenols (quercetin, resveratrol and silymarin), cultured probiotic microorganisms and drugs acting through direct/indirect or pleiotropic effects on glycemic control in DM. Among several options, we highlight new promising therapeutic coadjuvants, including chemical scavengers, the probiotic kefir and the phosphodiesterase 5 inhibitors, which besides the reduction of hyperglycemia and ameliorate insulin resistance, they reduce oxidative stress and improve endothelial dysfunction in the systemic vascular circulation. In the near future, experimental studies are expected to clear the intracellular pathways involving coadjuvants. The design of clinical trials may also contribute to new strategies with coadjuvants against the harmful effects of diabetic complications.
Highlights
Diabetes mellitus (DM) is an important public health issue because it is highly associated with increased morbidity and mortality [1]
Investigators have been challenged to test potential therapies for DM based on functional foods, which are of low cost and very accessible
Many studies have demonstrated that this bioflavonoid may act through diverse pathways to decrease the tissue-damaging effects of chronic hyperglycemia, such as stimulation of glucose uptake via GLUT4 [72,73,74], inhibiting hepatic glycogenolysis and gluconeogenesis [72,75], and inhibiting α-glucosidase in the small intestine [76] or intestinal glucose transporter GLUT2 [77]. Another potential advantage is that quercetin exhibits all the characteristics of an adequate antioxidant for diabetes treatment: free radical scavenger ability [78,79], long half-life (~20 h in humans) [80,81], capacity to suppress pro-oxidant enzymes (NADPH oxidase, xanthine oxidase and CYP) [82,83,84] and the ability to stimulate antioxidant enzymes (SOD, catalase, glutathione peroxidase and glutathione reductase) [68,85,86] with high mitochondrial permeability [46,87], which are an important source of reactive oxygen species (ROS) in diabetes [88,89]
Summary
Diabetes mellitus (DM) is an important public health issue because it is highly associated with increased morbidity and mortality [1]. The main issue of this pandemic is the increase in mortality associated with diabetes due to the risk of cardiovascular diseases (CVD), which are the leading cause of death in this population. With the mission of ameliorating this health problem, eight different classes of drugs for treatment of type 2 DM, with variations in their side effects and costs, have been approved by the US Food and Drug Administration (FDA) [9] In this regard, investigators have been challenged to test potential therapies for DM based on functional foods, which are of low cost and very accessible (e.g., substances derived from marine algae [10]). We discuss drugs with pleiotropic effects, such as phosphodiesterase 5 (PDE5) inhibitors, which lately have been the main focus of investigation in our laboratory
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