Diabetes is a growing problem. It was estimated that 8.3% of the United States population suffers from diabetes. The majority of diabetic patients suffer from type 2 diabetes (T2D). T2D is characterized by the onset of insulin resistance, which is commonly a consequence of obesity. An increase in inflammation and oxidative stress are part of the pathogenesis of T2D. Complications associated with T2D that can be attributed to immune dysfunction. Increased infection rates have been observed in epidemiological studies of diabetic individuals. Further, diabetic patients are at a greater risk of complications after infection. Innate immunity is an important part of host defense against tumor development and both viral and bacterial infections. Increases in the frequency of all these ailments in diabetic patients suggest that there is a decrease in the activity of the cells that are involved in innate immunity. Staphylococcus aureus is one of the most important pathogens affecting diabetic patients. Pneumonia caused by MRSA is a growing concern for diabetic patients. Infection with S. aureus is more likely to occur with increased glucose deregulation as measured by HbA1c levels. Mortality rates are higher for diabetic patients admitted for pneumonia. Colonization of diabetic foot ulcers with either S. aureus or MRSA may also be dependent on the nasal carriage of the patient compounding the importance for a rapid clearance of respiratory infections. Idiopathic pulmonary fibrosis is also mediated by oxidative stress. Production of ROS by NOX-4 potentiates myofibroblast activation and fibrogenesis in a mouse model of non-infectious lung injury. Rats with streptozotocin-induced diabetes had an increase in capillary endothelium hyperplasia and extracellular matrix when compared to non-diabetic controls; treatment with SOD reversed these effects. In patients suffering from idiopathic pulmonary fibrosis (IPF), diabetes has been shown to be one of the most important co-morbidities, along with cardiovascular disease and hypertension. Dysregulation of the renin angiotensin system (RAS) through chronic activation of the pathological signal from angiotensin II (A-II) is a component of diabetes. Angiotensin (1-7) [A(1-7)], a component of the RAS that counter-regulates A-II, has been shown to decrease inflammation, oxidative stress and fibrosis in a diabetic model. Safety trials in humans show that A(1-7) can be used with minimal risk of side effects. If A(1-7) can be used improve immune function and lung health in diabetic patients it may help ameliorate some of the disease states that are caused by diabetes.
There are many complications associated with T2D that can be attributed to increases in inflammation and oxidative stress. Innate immunity in the lung is an important part of host defense against both viral and bacterial infections and may be suppressed in diabetes due, in part, to dysregulation of the renin angiotensin system. Further damage is may be caused by the increase of fibrosis and inflammation. Treatment with A(1-7) may be able to reverse some of the damage and restore lung health.
| Papinska, Anna M; Soto, Maira; Meeks, Christopher J et al. (2016) Long-term administration of angiotensin (1-7) prevents heart and lung dysfunction in a mouse model of type 2 diabetes (db/db) by reducing oxidative stress, inflammation and pathological remodeling. Pharmacol Res 107:372-380 |
