sodium-nitrite and Diabetes-Mellitus--Type-1

Numerous factors may influence the incidence of diabetes in the population. The production of reactive oxygen species (ROS) is elevated in diabetes patients. Based on the reported involvement of reactive species and nitrate/nitrite in diabetes, this present study has examined in the alkaline Comet assay, the effect of different levels of NaNO(2) in the presence of the oxygen radical generating agent, hydrogen peroxide (H(2)O(2)). Peripheral lymphocytes from diabetic and non-diabetic Caucasians and Asians of both sexes were studied in vitro. Endogenous factors (e.g., sex, age, body mass index-BMI) and exogenous factors (lifestyle factors e.g., smoking and drinking habits, diet) were taken into account. A preliminary study in two individuals showed that DNA damage remained constant over a wide dose range of NaNO(2) (1-75mM), but when H(2)O(2) was added at a constant concentration of 50microM per dose of NaNO(2), there was an increase in DNA damage corresponding with the varying levels of NaNO(2) investigated. This was also seen with the 44 individuals (non-diabetic, n=24; type 1 diabetic, n=11; type 2 diabetic, n=9) investigated. NaNO(2) was capable of inducing a significant level of DNA damage in lymphocytes (p<0.001), but only with the addition of H(2)O(2). When levels of DNA damage were analysed in terms of the different variables there were few significant differences in damage between diabetic and non-diabetic subjects, or other sub-population groups, and no statistically significant differences in susceptibility were observed between subject covariates using regression techniques.

Topics: Adolescent; Adult; Aged; Asian People; Comet Assay; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; DNA Damage; Dose-Response Relationship, Drug; Drug Synergism; Female; Humans; Hydrogen Peroxide; In Vitro Techniques; Lymphocytes; Male; Middle Aged; Reactive Oxygen Species; Sodium Nitrite; United Kingdom; White People

Painful transcutaneous electrical nerve stimulation (TENS) of the foot dorsum evoked axon reflex vasodilatation, measured by laser Doppler flowmetry. In addition, acetylcholine (ACh) and sodium nitrite (NaNO2) were iontophoresed to cause vasodilatation by endothelium dependent and independent mechanisms, respectively. Compared with healthy volunteers, diabetic patients with clinically diagnosed neuropathy showed reduced electrical axon reflex flare and ACh responses, but not NaNO2 responses. Such reduced cutaneous nocifensor functions may contribute to some symptoms and complications of diabetes mellitus.

Topics: Acetylcholine; Adult; Aged; Axons; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Electric Stimulation; Humans; Lasers; Middle Aged; Reference Values; Reflex; Regional Blood Flow; Rheology; Skin; Sodium Nitrite; Vasodilation

The study was undertaken to determine whether the phenomenon of endothelium-dependent relaxation was impaired in the spontaneously diabetic BB Wistar rat. Endothelium-dependent relaxation in the aorta of overtly diabetic animals was compared with that in nondiabetic BB rats. The relaxative responses were elicited in vitro to acetylcholine (-8.0 to -5.5 log M) and histamine (-7.0 to -3.0 log M) after precontraction with norepinephrine (-6.0 log M). The maximum relaxations produced by both acetylcholine and histamine expressed as percentages of the contractions to norepinephrine were significantly lower in diabetic than in nondiabetic rats. Scanning electron microscopy revealed that in diabetic BB rats there was consistent evidence of swollen cells, raised nuclei, and sloughing of nuclei in endothelial cells of the aorta. In nondiabetic animals these features were not evident. These findings suggest the presence of a functional and morphological defect in endothelial cells in the aorta of the BB rat.

Topics: Acetylcholine; Animals; Aorta, Thoracic; Diabetes Mellitus, Type 1; Endothelium; Histamine; Microscopy, Electron, Scanning; Norepinephrine; Rats; Rats, Inbred BB; Sodium Nitrite; Vasodilation