Diabetes mellitus has been recognised as one of the four major non-communicable diseases that demands urgent attention from all key shareholders globally in an effort to address its prevalence and associated complications. It is considered as a top 10 cause of death globally, killing about 1.6 million people worldwide and is seen as the third highest risk factor for worldwide premature mortality due to hyperglycaemia and hyperglycaemic-induced oxidative stress and inflammation. There is a strong link between hyperglycaemia, hyperglycaemic-induced oxidative stress, inflammation and the development and progression of type 2 diabetes mellitus. Various reports have shown that chronic low-grade inflammation is associated with the risk of developing type 2 diabetes and that sub-clinical inflammation contributes to insulin resistance and is linked to the characteristics of metabolic syndrome which include hyperglycaemia. Oxidative stress stimulates the generation of inflammatory mediators and inflammation in turn enhances the production of reactive oxygen species. This interaction between diabetes, oxidative stress and inflammation is the primary motivation for the compilation of this review. Based on previous studies, the review examines the interaction between diabetes, oxidative stress and inflammation, factors promoting prevalence of diabetes mellitus, mechanisms involved in hyperglycaemia-induced oxidative stress with particular focus on type 2 diabetes and selected diabetic complications.

Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links.

Diabetes mellitus is a non-communicable disease that occurs in both developed and developing countries. This metabolic disease affects all systems in the body, including the liver. Hyperglycaemia, mainly caused by insulin resistance, affects the metabolism of lipids, carbohydrates and proteins and can lead to non-alcoholic fatty liver disease, which can further progress to non-alcoholic steatohepatitis, cirrhosis and, finally, hepatocellular carcinomas. The underlying mechanism of diabetes that contributes to liver damage is the combination of increased oxidative stress and an aberrant inflammatory response; this activates the transcription of pro-apoptotic genes and damages hepatocytes. Significant involvement of pro-inflammatory cytokines-including interleukin (IL)-1β, IL-6 and tumour necrosis factor-α-exacerbates the accumulation of oxidative damage products in the liver, such as malondialdehyde, fluorescent pigments and conjugated dienes. This review summarises the biochemical, histological and macromolecular changes that contribute to oxidative liver damage among diabetic individuals.

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Mechanisms of Diabetes-Induced Liver Damage: The role of oxidative stress and inflammation

Vitamin D Activates the Nrf2-Keap1 Antioxidant Pathway and Ameliorates Nephropathy in Diabetic Rats

Hypoglycemic and antioxidant effects of phenolic extracts and purified hydroxytyrosol from olive mill waste in vitro and in rats.

This review provides a current perspective on the mechanism of vitamin D on skeletal muscle function with the emphasis on oxidative stress, muscle anabolic state and muscle energy metabolism. It focuses on several aspects related to cellular and molecular physiology such as VDR as the trigger point of vitamin D action, oxidative stress as a consequence of vitamin D deficiency. The interaction between vitamin D deficiency and mitochondrial function as well as skeletal muscle atrophy signalling pathways have been studied and clarified in the last years. To the best of our knowledge, we summarize key knowledge and knowledge gaps regarding the mechanism(s) of action of vitamin D in skeletal muscle. Vitamin D deficiency is associated with oxidative stress in skeletal muscle that influences the mitochondrial function and affects the development of skeletal muscle atrophy. Namely, vitamin D deficiency decreases oxygen consumption rate and induces disruption of mitochondrial function. These deleterious consequences on muscle may be associated through the vitamin D receptor (VDR) action. Moreover, vitamin D deficiency may contribute to the development of muscle atrophy. The possible signalling pathway triggering the expression of Atrogin-1 involves Src-ERK1/2-Akt- FOXO causing protein degradation. Based on the current knowledge we propose that vitamin D deficiency results from the loss of VDR function and it could be partly responsible for the development of neurodegenerative diseases in human beings.

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Mechanisms of vitamin D on skeletal muscle function: oxidative stress, energy metabolism and anabolic state.

Diabetes mellitus is a major endocrine disorder and a growing health problem in most countries which can be ameliorated by numerous bio-molecules such as 1α,25 dihydroxyvitamin D3 [1α,25(OH)2VD3]. With this in mind, the current study investigated the therapeutic and preventive effects of 1α,25(OH)2VD3 on diabetes and its side effects: toxicity in liver, pancreas and kidneys. Our results show that administration of 1α,25(OH)2VD3 in diabetic rats increased the plasmatic insulin level, favored the normal blood glucose levels and normalized the hepatic glycogen concentration. In addition, 1α,25(OH)2VD3 enhanced superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) (by 207, 52 and 72%, respectively) compared to diabetic rats. It also reduced lipid peroxidation and the indices of toxicity in liver and kidneys by significantly decreasing alkaline phosphatases (PAL), aspartate and lactate transaminase (AST and ALT) activities, total and direct bilirubin, triglycerides (TG), cholesterol, creatinine, urea and iron levels in diabetic rats. Moreover, the plasmatic non-enzymatic antioxidant level of HDL-cholesterol, magnesium (Mg), calcium (Ca) and copper (Cu) increased after 1α,25(OH)2VD3 administration. The administration of 1α,25(OH)2VD3 in diabetic rats protects against alloxan-induced histological changes in pancreas. Conclusion: from these data, it is concluded that 1α,25(OH)2VD3 might be useful for the therapy and prevention of diabetes and the numerous side effects especially toxicity in liver, pancreas and kidneys and this protective effect is more obvious in our preventive experiment.

1α, 25 Dihydroxyvitamin D3 : Therapeutic and Preventive Effects against Oxidative Stress, Hepatic, Pancreatic and Renal Injury in Alloxan-Induced Diabetes in Rats

Hyperglycaemia, stress oxidant, liver dysfunction and histological changes in diabetic male rat pancreas and liver: Protective effect of 17β-estradiol

Objective: Aldosterone was involved in several metabolic disorders. Elevated levels were also reported in polycystic ovary syndrome (PCOS). Objective: to investigate aldosterone and metabolic abnormalities in PCOS at first discovery Design and method: we conducted a case-control study. First diagnosed PCOS patients were included with age and body mass index matched controls. Fasting blood samples were taken at the 3rd day of mezes. Aldosterone was assayed by ELISA DRG kit. The other parameters were dertemined by cobas 6000-Roche. Results: A total of 77 participants were enrolled: 41 PCOS and 35 controls. Aldosterone levels were significantly higher in PCOS. Median value in controls was 160ng/mL. We observed that 70% of aldosterone levels in PCOS were above this median value. Increased aldosterone levels were associated with elevated fasting glucose. Although, There was no significant difference in the prevalence of insulin-resistance, dyslipidemia, obesity, and metabolic syndrome between patients with different aldosterone levels distribution. Conclusions: Elevated aldosterone levels could be the primum movens activating carbohydrate metabolic alterations. Once elevated, aldosterone levels could give evidence of preclinic alterations at an early stage of PCOS.

Dorra Aloulou

Papers

1α, 25 Dihydroxyvitamin D3 : Therapeutic and Preventive Effects against Oxidative Stress, Hepatic, Pancreatic and Renal Injury in Alloxan-Induced Diabetes in Rats

Hyperglycaemia, stress oxidant, liver dysfunction and histological changes in diabetic male rat pancreas and liver: Protective effect of 17β-estradiol

Aldosterone in polycystic ovary syndrome