Background and Objectives: The present review critically discusses the high occurrence rate, insulin resistance and type-2 diabetes in tobacco exposed individuals. Tobacco extracts and smoke contain a large number of toxic materials and a significant number of those are metabolic disintegrators. Discussion: Glucose and lipid homeostasis is severely impaired by this compound. Tobacco exposure contributes to adverse effects by impairing the physical, biochemical and molecular mechanisms in the tissues. The immunological components are damaged by tobacco with high production of proinflammatory cytokines (IL-6, TNF-∞) and augmentation of inflammatory responses. These events result in damages to cytoskeletal structures of different tissues. Degradation of matrix structure (by activation of different types of MMPs) results in the permanent damages to the tissues and their metabolic functions. Cellular antioxidant defense system mostly cannot or hardly nullify CS-induced ROS production that activates polymorphonuclear neutrophils (PMNs), which are a major source of cytokines and chemokines (TNFα, IL6, IL8, INFγ). Additive effects of these immediately promote the low energy-metabolism as well as inflammation. Oxidative stress, mitochondrial dysfunction, and inflammation contribute to the direct nicotine toxicity via nAChRs in diabetes. The investigator identified that skeletal muscle insulin-resistance occurs in smokers due to phosphorylation of insulin receptor substrate1 (IRS1) at Ser-636 position. Conclusion: Tobacco exposure initiates free radical related immunological impairment, DNA damage, and inflammation. So, the present analysis is of importance to figure out the mechanistic layout of tobacco-induced tissue damage and its possible therapeutic interventions.

Chronic alcohol consumption has emerged as a leading cause of metabolic derangement in susceptible cohorts worldwide; ethanol has a high calorific value and excessive intake interferes with energy metabolism. It has a very high glycemic index, so the glucose homeostasis does not follow the normal physiological regulations in chronic consumption of ethanol. Chronic alcohol consumption is a global concern for its health issues. The detailed mechanism of alcohol-associated organ damage and health anomalies has been reviewed here. Almost all of its metabolic fates has minor to major impacts on any physiological process. The main rate-limiting markers of glucose homeostasis, i.e. NADH/NAD+ and ATP/ADP, are physiologically misjudged in ethanol consumption; as a result, excess acetoacetyl CoA becomes engaged in ketone body formation resulting in ketoacidosis. Ethanol induced ROS production and antioxidant depletion resulting in necrotic tissue damage especially in the stomach, intestine epithelial cells, and liver. Increased oxidative stress causes vascular dysfunction, NO deregulation, peripheral vascular resistance, increased blood pressure, and aldosterone-induced hypertension. Ethanol manipulates intracellular phosphorylation regulations by influencing MAPK and inflammatory molecule, like TNFa and IL-6, and transcriptional stress factor like NF-κβ, Nrf-2, and Hif-α via redox signalling. Activation of lipogenic factors and PPAR signalling drastically increase body fat accumulation. Direct damage to the pancreatic cells generates insulin resistance. Synergistic effects of several metabolic malfunctioning develop insulin resistance, chronic hyperglycaemia, and abnormal fat accumulation.