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.

The aggregation of platelets on the plaque rupture site on the coronary artery is reported to cause both acute coronary syndromes (ACS) and acute myocardial infarction (AMI). While the inhibition of platelet aggregation by acetyl salicylic acid was reported to produce beneficial effects in ACS, it failed to do in AMI. The concentration of a stress induced protein (dermcidin isoform-2) was much higher in AMI than that in ACS. Incubation of normal platelet rich plasma (PRP) with dermcidin showed one high affinity (Kd = 40 nM) and one low affinity binding sites (Kd = 333 nM). When normal PRP was incubated with 0.4 μM dermcidin, the platelets became resistant to the inhibitory effect of aspirin similar to that in the case of AMI. Incubation of PRP from AMI with dermcidin antibody restored the sensitivity of the platelets to the aspirin effect. Incubation of AMI PRP pretreated with 15 μM aspirin, a stimulator of the NO synthesis, resulted in the increased production of NO in the platelets that removed the bound dermcidin by 40% from the high affinity binding sites of AMI platelets. When the same AMI PRP was retreated with 10 μM aspirin, the aggregation of platelets was completely inhibited by NO synthesis.

Tbe early (10 minute) immunoreactive insulin release in response to various stimuli in patients with severe pancreatic exocrine insufficiency was compared to controls. The mean 10 minute incremental area of the response to combined glucose, glucagon and tolbutamide was severely reduced in patients (728 ± 287.7 vs 2714 ± 479.91-(U minutes; p < 0.0025). Mean insulin responses to oral glucose were similar in patients and controls, but the insulin response to intravenous glucose was absent in 4 of 6 patients (patients 79.0 ± 51.2 vs controls 874 ± 171.9 I-(U/minutes; p < 0.0025). All patients retained some insulin responsiveness to intravenous arginine. Intravenous secretin produced an insulin response in all patients (57.6 ± 17.6 and controls 220 ± 70.81-(U minutes; p < 0.05). Cholecystokinin pancreozymin (CCK-PZ) produced an insulin response in 5 of 6 patients (38 ± 17.9 vs 158 ± 30.7 I-(U minutes; p < 0.005). It is concluded that in chronic pancreatitis-(1) the beta cell glucose sensitive mechanism may be defective, while the glucose-stimulated pathway of the entero-insular axis is maintained; (2) Arginine-induced insulin secretion is mediated different-Iy from the intravenous g1ucose-induced response; (3) insulin responses to Secretin and CCK-PZ are retained, which may partially explain the insulin response to oral glucose.

The outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global catastrophe. The elderly and people with comorbidity are facing a serious complication of the disease. The entry and infection strategy of SARS-CoV-2 in a host cell is raised by an amazing way of angiotensin-converting enzyme (ACE) 2 (ACE2) receptor recognition and imbalance of ACE/ACE2 in various organs, especially in the lungs. Here it has been discussed the role of interferon and protease during the receptor recognition (begining of infection) and followed by the impact of cytokine and hypoxia in the context of the balance of ACE/ACE2. It has also very concisely delineated the biochemistry and mechanism of ACE/ACE2 balance in different stages of infection and its role in comorbidity.