Matching Diabetes and Alcoholism: Oxidative Stress, Inflammation, and Neurogenesis Are Commonly Involved

Figure 1

Scheme summarizing common pathways implicated in oxidative stress, inflammation, and antioxidant responses. 1. Circulating ethanol and high glucose levels lead to ROS production, antioxidant defense decay, AGE, and aldehyde production (4-HNE, MDA). Alterations on the hypothalamic pituitary axis (HPA) produce glucocorticoid release. 2. RAGE activation and ROS activate Akt but increased levels of 4-HNE; MDA can block Akt phosphorylation. 3. CBP is an acetyl transferase (HAT) that depends on p-Akt. CBP is necessary for p-CREB, Nf-κB, and Nrf2 allowing transcription of proinflammatory or anti-inflammatory genes. Glucocorticoid receptors inhibit CBP activity blocking transcription. Since Nf-κB, p-CREB, and Nrf2 compete for CBP the balance on proinflammation versus anti-inflammation transcription is compromised. GSH: reduced glutathione; NF-κB: nuclear factor kappa B; MDA: malondialdehyde; ROS: reactive oxygen species; MnSOD: manganese superoxide dismutase; TNFα: tumor necrosis factor alpha; COX: cyclooxygenase; iNOS: inducible nitric oxide synthase; GPx: glutathione peroxidase; BDNF: brain-derived neurotrophic factor; NGF: nerve growth factor; Bcl-2: B-cell lymphoma 2; CORT: corticosteroid; CORT-R: corticosteroid receptor; P-CREB: phospho-cAMP response element-binding; CBP: CREB-binding protein; Nrf2: nuclear factor erythroid-derived 2; 4-HNE: 4-hydroxynonenal; Akt: protein kinase B; CYP2E1: cytochrome P450 2E1; RAGE: receptor for advanced glycation end products.