Oxidative stress, inflammation, and metabolic dysregulation in type 2 diabetes: Therapeutic potential of Carica papaya

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterised by progressive insulin resistance, β-cell dysfunction, chronic hyperglycaemia, oxidative stress, and low-grade inflammation. These disturbances disrupt metabolic signalling pathways in the liver, skeletal muscle, adipose tissue, and kidney, contributing to impaired glucose homeostasis and the development of vascular and metabolic complications. Although current therapies improve glycaemic control and reduce cardiometabolic risk, they do not fully address the interconnected molecular mechanisms driving disease progression. This narrative review summarises the major molecular pathways involved in T2DM pathogenesis, with emphasis on dysregulation of IRS–PI3K/AKT and AMPK signalling and their interactions with oxidative stress- and inflammation-related pathways, including Nrf2, JNK, and NF-κB. Tissue-specific alterations in hepatic glucose production, skeletal muscle glucose uptake, adipose dysfunction, and renal glucose handling are discussed within an integrated metabolic framework. Recent advances in T2DM management, including SGLT2 inhibitors and incretin-based therapies, are also reviewed in relation to their metabolic and organ-protective effects. To illustrate the potential of multi-target interventions, Carica papaya is presented as a focused case study. Recent experimental evidence (2020–2025) indicates that extracts and phytochemical fractions from different parts of C. papaya modulate pathways involved in glucose metabolism, oxidative stress, and inflammatory signalling. Reported effects include enhanced glucose uptake, activation of AMPK and insulin-signalling pathways, attenuation of NF-κB- and JNK-mediated inflammation, and improved antioxidant responses through Nrf2-associated mechanisms. However, current evidence remains largely preclinical and is limited by variability in extract preparation, lack of standardisation, limited bioavailability data, and absence of human clinical studies. Overall, this review highlights oxidative stress and inflammation as central drivers of metabolic dysfunction in T2DM and emphasises the need for multi-target therapeutic strategies. While C. papaya demonstrates promising mechanistic relevance, further standardisation, pharmacokinetic evaluation, toxicological assessment, and clinical validation are required before translational application can be established.