Estriol Inhibits Dermcidin Isoform-2 Induced Inflammatory Cytokine Expression Via Nitric Oxide Synthesis in Human Neutrophil.

BACKGROUND: An increase in the level of cytokines like TNF-α and IL-6 causes the inflammatory surge in acute ischemic heart disease (AIHD). OBJECTIVE: A high-level dermcidin isoform-2 (DCN-2) occurrence in AIHD was subjected to determine a possible regulation of cytokines expression. The effect of estrogen to counteract the inflammatory response was determined. METHODS: Blood was collected from AIHD patients and normal volunteers with consent. Nitric oxide (NO) synthesis was done with methemoglobin method.TNF-α and IL-6 expression were determined by ELISA and Western blot. RESULTS: (DCN-2) incubation with 120nM to the normal neutrophil solution for 2h resulted in the increase of TNF-α from 3.82±1.53pg/ml to 20.7±6.9pg/ml and IL-6 from 3.27±1.52pg/ml to 47.07±3.4pg/ml. In AIHD patients, the cytokine level was18.3- 27.3pg/ml, with a median value 21.86pg/ml (TNF-α) and IL-6 level was 23.54- 52.73pg/ml, with a median value 42.16pg/ml. Treatment with 0.6nM estriol, a kind of female steroid hormone estrogen for 45min decreased the elevated cytokine level in 120nM DCN-2 treated normal neutrophils. DCN-2 induced TNF-α synthesis in neutrophils was further determined by Western blot technique with a thickened band intensity of TNF-α. Estriol (0.6nM) treatment also influenced the DCN-2 induced inhibition of nitric oxide (NO) synthesis from 0nmol NO/ml to 0.56nmol/ml. The subsequent reduction of TNF-α level correlates the increase of NO level. CONCLUSION: In conclusion, the stress-induced DCN-2 production in AIHD propagates the inflammatory response. Steroid molecule like estriol plays a protective role by reducing DCN-2 responses in the NO synthesis.

The role of Dermcidin isoform-2 in the occurrence and severity of Diabetes.

Diabetes is now epidemic worldwide. Several hundred-million peoples are presently suffering from this disease with other secondary-disorders. Stress, hypertension, sedentary life-style, carbohydrate/lipid metabolic-disorders due to genetic or environmental factors attributes to type-1 and/or type-2 diabetes. Present investigation demonstrates that stress-induced protein dermcidin isoform-2 (DCN-2) which appears in the serum of diabetic-patients play a key-role in this disease pathogenesis/severity. DCN-2 suppresses insulin production-release from liver/pancreas. It also increases the insulin-resistance. Stress-induction at the onset/progression of this disease is noticed as the high-level of lipid peroxides/low-level of free-thiols in association with increase of inflammatory-markers c-reactive protein and TNF-α. DCN-2 induced decrease in the synthesis of glucose-activated nitric oxide synthase (GANOS) and lower production of NO in liver has been shown here where NO is demonstrated to lower the expression of glucose trabsporter-4 (GLUT-4) and its translocation on liver membrane surface. This finally impairs glucose transport to organs from the extracellular fluid. Low level of glucose uptake further decreases glucose-induced insulin synthesis. The central role of DCN-2 has been demonstrated in type-1/type-2 diabetic individuals, in rodent hepatocytes and pancreatic-cell, tissue-slices, in-vitro and in-vivo experimental model. It can be concluded that stress-induced decrease in insulin synthesis/function, glucose transport is an interactive consequence of oxidative threats and inflammatory events.

Diabetes in rural individuals of different nutritional status and the alarming situation demands focus more on its under-nutrition association.

OBJECTIVE: To study the relationship of nutritional-status with diabetes. DESIGN: The socioeconomics/anthropometrics, blood-glucose/systemic-hypertension are evaluated in consecutively-selected diabetic-patients. SETTING: Semi-urban/rural India. SUBJECTS: Hyperglycaemic patients (total 90/male 37). RESULTS: Blood-glucose (PP-mean ± SE) in individuals is overweight - 38.89% (226.94 ± 9.59), normal-weight - 50% (217.58 ± 1.34), underweight - 11.11% (305.50 ± 21.35) indicating most hyperglycaemia in undernourished-group (F = 6.357, p < 0.003). This group occupies higher glucose-groups in ≤140, 141-270, and ≥270 mg/dL. The blood-glucose negatively correlates with waist(r = -0.282; p < 0.01) and hip (r = -0.254; p < 0.05) circumference indicating the under-nutrition association with glucose-homeostasis (F = 7.6-8.2, p < 0.001). The higher glucose is noticed in more number of individuals in lower (<40 years) age-group (χ(2 )= 12.86; p < 0.002/ρ = -0.355; p < 0.001). The prevalence of hypertension is 28% (underweight = 20%, overweight = 27%, normal = 30%). The group of 141-270 mg/dL glucose has 45% and rest groups together have 23% hypertensive individuals relating directly, hypertension and diabetic-onset. CONCLUSIONS: Diabetes, explored in <40 years group and even more in female should be extensively studied accounting WHO categorization (1985/TRS/727) of malnutrition related diabetes (MRDM). Further, different interactive risk-factors should be properly addressed and the global-malnutrition/gender-based inequities be eradicated.