Most human cells utilize glucose as the primary substrate, cellular uptake requiring insulin. Insulin signaling is therefore critical for these tissues. However, decrease in insulin sensitivity due to the disruption of various molecular pathways causes insulin resistance (IR). IR underpins many metabolic disorders such as type 2 diabetes and metabolic syndrome, impairments in insulin signaling disrupting entry of glucose into the adipocytes, and skeletal muscle cells. Although the exact underlying cause of IR has not been fully elucidated, a number of major mechanisms, including oxidative stress, inflammation, insulin receptor mutations, endoplasmic reticulum stress, and mitochondrial dysfunction have been suggested. In this review, we consider the role these cellular mechanisms play in the development of IR.

It has been reported that oxidative stress has a pivotal role in many disorders such as chronic kidney diseases. Free radicals can directly attack cellular elements, trigger intracellular signaling pathways, or induce systemic responses leading to renal damages. In the current review, we evaluated the literature focusing on the main recognized effects of oxidative stress on the pathophysiology of chronic renal disorders. We searched the PubMed-Medline and Scopus databases by using the following key words: oxidative stress, kidney, chronic kidney diseases, and free radicals and found about 200 related articles. Then, we focused on the molecular mechanisms underlying chronic kidney diseases which can be induced by oxidative stress and explored how free radicals stimulate these mechanisms. By reviewing the literature, we found that there are almost nine important molecular pathways through which free radicals influence the renal function. Based on the retrieved data, oxidative stress has an important role in the pathophysiology of chronic kidney diseases. Understanding these pathophysiologic pathways may lead us to find new approaches for the management of these debilitating disorders.

Glucagon-like peptide-1 receptor (GLP-1R) agonists are a class of newly introduced antidiabetic medications that potentially lower blood glucose by several molecular pathways. DPP-4 inhibitors are the other type of novel antidiabetic medications which act by preventing GLP-1 inactivation and thereby increasing the activity levels of GLP-1, leading to more glucose-induced insulin release from islet β-cells and suppression of glucagon release. Most patients with diabetes have concurrent hypertension and cardiovascular disorder. If antihyperglycemic agents can attenuate the risk of hypertension and cardiovascular disease, they will amplify their overall beneficial effects. There is conflicting evidence on the cardiovascular benefits of GLP-1R induction in laboratory studies and clinical trials. In this study, we have reviewed the main molecular mechanisms by which GLP-1R induction may modulate the cardiovascular function and the results of cardiovascular outcome clinical trials.