New Advances on Pathophysiology of Diabetes Neuropathy and Pain Management: Potential Role of Melatonin and DPP-4 Inhibitors

Abstract

Pre-diabetes and diabetes are growing threats to the modern world. Diabetes mellitus (DM) is associated with comorbidities such as hypertension (83.40%), obesity (90.49%), and dyslipidemia (93.43%), creating a substantial burden on patients and society. Reductive and oxidative (Redox) stress level imbalance and inflammation play an important role in DM progression. Various therapeutics have been investigated to treat these neuronal complications. Melatonin and dipeptidyl peptidase IV inhibitors (DPP-4i) are known to possess powerful antioxidant and anti-inflammatory properties and have garnered significant attention in the recent years. In this present review article, we have reviewed the recently published reports on the therapeutic efficiency of melatonin and DPP-4i in the treatment of DM. We summarized the efficacy of melatonin and DPP-4i in DM and associated complications of diabetic neuropathy (DNP) and neuropathic pain. Furthermore, we discussed the mechanisms of action and their efficacy in the alleviation of oxidative stress in DM.

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

“…It was discovered that it directly reacts with the superoxide anions as ascorbic acid under ROS physiological conditions. It was discovered to reduce oxidative damage and enhance the antioxidant capacity of various antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione levels (GSH), and glutathione peroxidase (GPx) [ 37 , 38 ]. Recent research has shown that CA can be used as a supplement to reduce cytokine release and, as a result, inflammation in humans [ 39 ].…”

Comparative study of aqueous, methanol and petroleum ether extracts of unripe Carica papaya seed on liver and kidney function in streptozotocin-induced diabetic rats

“…Diabetes affects many organs, including the liver, which plays a key role in the regulation of carbohydrate, lipid, and protein metabolism 4,6,23,24 . Elevated serum aminotransferases level; aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyltransferase (γ-GT) which was observed in this study due to induction of diabetes was in line with other precious findings on diabetes [25][26][27] .…”

“…Concern regarding this chronic disease is the complications which can affect multiple vital organ systems, thereby leading to more severe and irreversible pathological conditions such as nephropathy, retinopathy, vasculopathy, neuropathy and cardiovascular diseases, as well as hepatopathy [1][2][3] . Research indicates that DM is associated with a number of liver abnormalities, such as abnormal glycogen deposition, non-alcoholic fatty liver disease (NAFLD), fibrosis, cirrhosis, hepatocellular carcinomas (HCCs), abnormal elevated hepatic enzymes, acute liver disease and viral hepatitis [4][5][6] . A fatty liver and hyperglycaemia can destroy the hepatocytes and contribute to increased morbidity and mortality among diabetic patients 4,7 .…”