Abstract
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.
Highlights
Diabetes mellitus, a global public health problem is emerging as an epidemic worldwide[1]
When the liver cell homogenate was incubated with both glucose and 0.2 μM dermcidin isoform-2 (DCN-2), the expression of both pro-insulin genes I and II was reduced (Fig. 7c, lane-2). These results suggested that environmental stresses, oxidative stresses, reduced production of anti-oxidants, products generated from lipid peroxidation and autoimmunity are key factors in the genesis of both type-1-diabetes mellitus (T1DM) and type-2-diabetes mellitus (T2DM)
We have recently reported that a stress induced protein identified to be dermcidin isoform-2 (DCN-2) appeared in the circulation of Type-1B-diabetes mellitus (T1BDM) patients which lack immunological markers[10]
Summary
A global public health problem is emerging as an epidemic worldwide[1]. The T1BDM on the other hand, has been reported to be induced by stress or other environmental factors. It has been reported that the T1BDM occurred as a major form of T1DM due to dermcidin induced inhibition of glucose uptake, rather than destruction of the pancreatic β cells[11]. Patients suffering from acute myocardial infarction (AMI) have high level of DCN-2 in their plasma[11, 12]. As because diabetes is the major risk factor for the genesis of AMI and atherosclerosis, so, diabetic patients (both type-1 and type-2) have high level of DCN-2 in their plasma. Stress induced genesis of diabetes in patients is reported[10]. From our laboratory that high altitude illness may augment plasma level of DCN due to environmental stress[13]. In all these instances stress and DCN have been correlated to the patho-physiological conditions
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