Due to the importance of glycation in the genesis of diabetic complications, there is an intensive search for new synthetic antiglycative agents. However, a somewhat neglected approach is the search for endogenous compounds that can inhibit the process and become a source of protopreparations. Based on their ubiquitous distribution, their polycationic nature, their significant role in growth, their relatively high concentrations in tissues and their high concentrations in spermatozoa, we assumed that polyamines inhibit glycation and that this may be one of their hitherto elusive functions. In this study, we demonstrate the potent anti-glycative effect of physiological concentrations of polyamines, spermine and spermidine.
Diabetes mellitus is a metabolic disease characterized by insufficient insulin secretion. Polyamine oxidase (PAO), a FAD-containing enzyme, is involved in the biodegradation of Sp and Spd, catalyzing the oxidative deamination of Sp and Spd, which leads to the formation of ammonia (NH3) corresponding to amino aldehydes and H2O2. Malonic aldehyde (MDA) and acrolein (CH2 = CHCHO), potentially toxic agents that cause oxidative stress in mammalian cells, then spontaneously form from amino aldehydes. The main signs of oxidative stress in children with diabetes were the values of HbA1c and MDA levels. Polyamines have an insulin-like effect. The antiglastic properties of spermine and spermidine have recently been confirmed.
Correlation analysis revealed a significant positive relationship between fasting and spermine insulin levels. Multiple logistic regression analysis (taking into account age, gender, and body mass index) showed that serum putrescine and spermine levels were associated with a higher risk of developing diabetes. Findings. Our study shows that the metabolism of polyamines is disturbed in T2DM.
There was a decrease in autophagy in cardiomyocytes in type 2 diabetes mellitus.
NR (NAD +)
Treatment with high doses of nicotinamide (niacinamide, vitamin B3) prevents or delays insulin-deficient diabetes in several animal models with type 1 diabetes and protects islet cells from the cytotoxic effect in vitro. With newly developed type 1 diabetes, administration of nicotinamide improves the function of beta cells without significantly reducing the need for insulin.
NR improved glucose tolerance, reduced weight gain, liver damage and the development of liver steatosis in pre-diabetic mice, while protecting against sensory neuropathy. In T2D mice, NR significantly reduced fasting and fasting blood glucose levels, increased liver weight and steatosis, while protecting against diabetic neuropathy.
Nicotinamide can protect the NOD mouse from diabetes if it is taken early enough and in sufficient dose. The effect is partially reduced with time. Inflammation of the islets is reduced. Such protective effects can be demonstrated in quasi-experimental human interventions — both diabetic and non-diabetic — that are considered to be at risk of developing diabetes due to the presence of antibodies to islet cells. Nicotinamide protects isolated islets in vitro from the toxicity of a number of agents, but only at doses that cause significant inhibition of PARP and increase intracellular levels of NAD. The drug is safe in doses used in humans.
The introduction of IIT (intensive insulin therapy) with the addition of nicotinamide during diagnosis, which lasted for 2 years, improves the metabolic control according to HbA1c. A decrease in C-peptide was not detected 2 years after diagnosis, which indicates that IIT and nicotinamide retain C-peptide secretion.
The use of NR increases the bioavailability of NAD +, which leads to the activation of SIRT1 and protection against metabolic diseases. Here, we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), the recently described natural precursor NAD + with the ability to increase the levels of NAD +, Sir2-dependent silence of the genes and the replicative lifespan of yeast. We show that adding NR in mammalian cells and mouse tissues increases NAD + levels and activates SIRT1 and SIRT3, which leads to increased oxidative metabolism and protection against metabolic disorders caused by a high-fat diet. Consequently, our results show that natural vitamin NR can be used as a food additive to improve metabolic and age-related disorders characterized by impaired mitochondrial function.
A clinical study conducted at the University of Copenhagen, Aarhus University Hospital and the University of Iowa, provided the first human evidence of the potential of nicotinamide riboside (HP) to improve human health in obesity.
RESTORES THE SECRETION OF INSULIN
In the white adipose tissue of mice, it activates the enzyme UCP1, which can contribute to lipolysis and normalization of body weight.
Fucus vesiculosus water and ethanol extracts are able to inhibit α-glucosidase activity in vitro with 50% inhibition at 0.32 μg / ml with water and 0.49 μg / ml with ethanol extracts, respectively. Inhibition of α-glucosidase and PTP1B activity leads to a decrease in plasma glucose levels and an enhanced insulin action. Inhibition of the formation of AGE and the activity of aldemoreductase is another approach that is currently being studied in the treatment of hyperglycemia with the use of algae.
Fucoxanthin reduces the expression of MCP-1 mRNA, PAI-1, IL-6 and TNF-α in white adipose tissue of diabetic KK-Ay mice. Fucoxanthinol reduced the over-expression of iNOS and COX-2 mRNA in macrophage-like RAW264.7 cells, and also reduced the overexpression of MCP-1 and IL-6 mRNA during the differentiation of 3T3-F442A adipocytes in vitro. Fucoidan also reduces the expression of MCP-1, PAI-and TNF-α during adipogenesis in 3T3-L1 cells in vitro. High levels of pro-inflammatory cytokines, such as PAI-1, IL-6, TNF-α and reduced secretion of anti-inflammatory IL-10, are associated with increased insulin resistance. Fucoidan and fucoxanthin have a pronounced anti-diabetic effect through various molecular pathways.
As a result of in vivo studies, the anti-diabetic activity of fucoxanthin was shown in a group of mice (Maeda et al., 2007). Fucoxanthin markedly reduced blood glucose and plasma insulin, as well as water consumption.
diabetic / obese mice of the KK-Au line. It is suggested that this carotenoid improves insulin resistance and reduces the blood glucose level, at least partially, through adipokine downregulation (tumor necrosis factor-a, interleukin-6, inhibitor plasminogen activator-1), directly acting on adipocytes and macrophages in white adipose tissue with increased regulation
GLUT-4 in skeletal muscle in mice (Peng et al., 2011; D’Orazio et al., 2012). The study group of mice for 4 weeks was given food with fucoxanthin concentration of 0.1 and 0.2%. At the same time, blood glucose levels, insulin levels and concentration were recorded.
leptin in serum. As a result, these indicators were significantly lower in the fucoxanthin group compared with the control group (Maeda et al., 2007; Park et al., 2011).
NARINGIN / NARINGININ
It has anti-diabetic effect, reduces insulin resistance, warns and treats obesity. More details: http://young-life.ru/science/naringin/