Implications of magnesium deficiency in type 2 diabetes: a review.

Magnesium is the fourth most abundant cation in the body and plays an important physiological role in many of its functions. It plays a fundamental role as a cofactor in various enzymatic reactions involving energy metabolism. Magnesium is a cofactor of various enzymes in carbohydrate oxidation and plays an important role in glucose transporting mechanism of the cell membrane. It is also involved in insulin secretion, binding, and activity. Magnesium deficiency and hypomagnesemia can result from a wide variety of causes, including deficient magnesium intake, gastrointestinal, and renal losses. Chronic magnesium deficiency has been associated with the development of insulin resistance. The present review discusses the implications of magnesium deficiency in type 2 diabetes.

Effect of a low magnesium diet on in vitro glucose uptake in sucrose fed rats.

Dietary magnesium deficiency and excess sucrose in the diet have been shown to play an important role in the development of insulin resistance. This study is an extension of a previously published experiment (Magnes Res 2004; 17: 293-300) and is focused on the effect of a low magnesium diet on in vitro glucose uptake in sucrose fed rats. For this purpose male Wistar rats were divided into four groups and fed control, high sucrose, low magnesium and high sucrose low magnesium diets for a period of three months. Serum and erythrocyte magnesium values demonstrated a significant drop in the low magnesium and high sucrose low magnesium groups. A significant increase was observed in the body weight of the high sucrose group, whereas the weights of animals in the high sucrose low magnesium group remained unchanged from controls. The biochemical analysis showed a significant decrease in in vitro glucose uptake in liver, muscle and diaphragm of rats consuming high sucrose, low magnesium and high sucrose low magnesium diets. The maximum reduction, however, was observed in the combined high sucrose low magnesium group. These findings seem to suggest the potential of a high sucrose low magnesium diet to cause insulin resistance by reducing glucose uptake in target tissues of rats.

Implications of oxidative stress in high sucrose low magnesium diet fed rats.

BACKGROUND: Magnesium deficiency as well as excess sucrose in the diet have been shown to be associated with the generation of reactive oxygen species (ROS). AIM OF THE STUDY: In the present study we have investigated the combined effect of low magnesium high sucrose diet on the development of oxidative stress in rats. METHODS: Male Wistar rats were divided into four groups and fed control (C), low magnesium (LM), high sucrose (HS) and low magnesium high sucrose (HSLM) diet for a period of 3 months. Levels of various antioxidants, viz. ascorbic acid, vitamin E, uric acid, glutathione and non-protein thiols were determined along with malondialdehyde levels (lipid peroxidation marker). Anti-oxidant enzyme activities were determined in livers of experimental diet fed animals. RESULTS: Compared to controls, significantly increased lipid peroxidation was observed in plasma and liver tissue of animals in the three experimental groups, however, the combined HSLM group showed greater lipid peroxidation. Levels of various antioxidants fell significantly in plasma and tissue of LM, HS and HSLM rats. Total thiols as well as liver non-protein thiols followed a similar trend with the greatest drop in anti-oxidant potential seen in the HSLM rats. The activities of the anti-oxidant enzymes viz. SOD, GST and catalase also declined considerably in test animals w.r.t controls, with the HSLM group showing the lowest activities. CONCLUSION: These findings suggest that a diet low in magnesium and high in sucrose causes oxidative stress in rats, as reflected by increased lipid peroxidation and reduced anti-oxidant potential.

Insinuation of exacerbated oxidative stress in sucrose-fed rats with a low dietary intake of magnesium: evidence of oxidative damage to proteins.

High sucrose diets and low magnesium intake have been independently implicated in induction of oxidative stress in animal models. The aim of this study was to investigate whether low dietary magnesium intake exacerbates the prooxidant effects of high sucrose feeding. Rats were fed control (C), high sucrose (HS); low magnesium (LM) and high sucrose low magnesium (HSLM) diets for 90 days and oxidative stress evaluated in terms of formation of TBARS, advanced oxidation protein products and protein carbonyls. HS and LM rats showed evidence of lipid peroxidation and protein oxidation in plasma and liver. Enhanced oxidative injury to lipids and proteins after HSLM feeding was indicated by increased carbonyl content (p <0.01) and significantly (p <0.005) higher levels of TBARS in plasma and hepatic tissue relative to both HS and LM groups. Altogether, these results illustrate the potential detrimental and cumulative effects of low magnesium intake combined with high sucrose consumption on oxidative stress variables.

Effect of vitamin E supplementation on diabetes induced oxidative stress in experimental diabetes in rats.

Diabetes induced by streptozotocin (50 mg/kg body wt, i.p.) in the rats substantially increased the plasma glucose and malondialdehyde levels along with corresponding decrease in the antioxidants levels. Supplementation of vitamin E (200 mg/kg body wt., ip) for 5 weeks resulted in non-significant decrease in the blood glucose levels but plasma malondialdehyde levels were reduced to below normal levels. Plasma vitamin E, vitamin C, uric acid and red blood cell glutathione levels were also restored to near normal levels on vitamin E supplementation to diabetic rats as compared to control (diabetic) rats. The activities of antioxidant enzymes, catalase (EC 1.11.1.6), glutathione peroxidase (GSHPx EC 1.11.1.9), and glutathione reductase (GR EC 1.6.4.2) were also concomitantly restored to near normal levels by vitamin E supplementation to diabetic rats. The results clearly demonstrated that vitamin E supplementation augments the antioxidant defense mechanism in diabetes and provides evidence that vitamin E may have a therapeutic role in free radical mediated diseases.

Evidence of free radical participation in N-glycolylneuraminic acid generation in liver of chicken treated with gallotannic acid.

The occurrence of N-glycolylneuraminic acid (Neu5Gc) in cancerous tissue and inflammatory diseases, conditions associated with increased oxidative stress suggests the participation of reactive oxygen radicals in Neu5Gc generation, where an oxygen atom is transferred. To study this possibility, we treated two groups of domesticated birds and rabbits with different dosages of gallotannic acid (GTA), a compound known to cause generation of reactive oxygen species (ROS). The antioxidant status and leukocyte capacity, as well as amount and form of sialic acids were assessed in plasma and liver. Results showed that while lipid peroxides were increased, white blood cell (WBC) count was decreased significantly in all treated groups. The increased sialic acids and low protein contents were observed in plasma, possibly as a result of decreased sialic acid cycling crucial for formation of new glycoconjugates in tissues, caused by decreased protein synthesis due to microsomal degranulation. The activities of antioxidant enzymes were also decreased in treated groups, implying increased oxidative stress. The presence of Neu5Gc and apparent absence of Neu5Ac hydroxylase activity in liver of chicken treated with GTA indicate that free radicals might be involved in the non-enzymatic hydroxylation of N-acetylneuraminic acid (Neu5Ac) to Neu5Gc in liver, which normally does not express this sialic acid.

Effect of magnesium supplementation on oxidative stress in alloxanic diabetic rats.

Magnesium deficit and oxidative stress are common features of the diabetic state. This concept supported by another observation that magnesium deficiency is also a state of increased oxidative stress prompted us to study the effect of magnesium supplementation on magnesium status and oxidative stress in diabetic rats. For this purpose, male Wistar rats were made diabetic with a single intraperitoneal injection of Alloxan. Experimental diabetes caused a significant decrease in serum and red blood cell magnesium levels and increased urinary excretion of magnesium. Marked increase in plasma malondialdehyde and corresponding decrease in vitamins C & E, uric acid and total thiols was observed in the diabetic rats as compared to control group. In liver, MDA levels were increased significantly with concomitant decrease in vitamin C, non-protein thiols and antioxidant enzymes (SOD & GST). Magnesium supplementation for four weeks restored serum and RBC magnesium levels to near normal levels with marginal but significant decrease in blood glucose levels. Plasma and liver MDA levels were reduced significantly and vitamin C and total thiols were increased significantly with magnesium supplementation. Antioxidant enzyme activity was also increased significantly with magnesium supplementation in diabetic rats. Our data clearly demonstrates that alloxanic diabetes is associated with decreased magnesium status and increased oxidative stress and that magnesium supplementation can in part restore the antioxidant parameters and decrease the oxidative stress in experimental diabetic rats.

N-glycolylneuraminic acid conjugates: implications of their absence in mammalian biochemistry.

N-glycolylneuraminic acid (Neu5Gc) is one of the two most common forms of sialic acids present in glycoproteins and glycolipids of mammalian tissues. It is synthesized from the most ubiquitous sialic acid, N-acetylneuraminic acid (Neu5Ac) in a hydroxylation reaction catalysed by the enzyme Neu5Ac hydroxylase. Though Neu5Gc conjugates are prevalent in many tissues of mammals, they are absent in glycolipids and only trace amounts are present in glycoproteins of the brain and central nervous system. In humans Neu5Ac is the main sialic acid as Neu5Ac hydroxylase is inactive due to mutation of its gene. The importance of sialic acids in biochemical phenomena and the distinct roles played by specific forms of these amino sugars is adequately reflected in functional studies of selectin and sialoadhesin families of adhesion molecules. The absence of Neu5Gc, therefore, in tissues of humans and brain of mammals has raised interest, especially with regard to its impact on biochemical differences evident between humans and other mammals. It is suggested that though Neu5Gc conjugates are important in cellular interactions, their presence in brain and the central nervous system is deleterious to the latter's normal functions. Their interaction with other cellular components to form supramolecular associations is indicated that may have a bearing on major biochemical differences, a few of which are presently evident between humans and other mammals.