Mellitus Oxidative Stress

Diabetes is a complex disease which bonds together evolution and environmental factors and creates many health issues for humans. Diabetes (mellitus) is classified into three groups of metabolic diseases that involves high blood sugar (glucose) and it can occur in different ways depending on circumstances. Type 2 diabetes occurs when cells do not function correctly, and evidently the cells do not properly respond to insulin. Type 1 diabetes involves the body’s inadequate production of insulin, which is commonly referred to as insulin-dependent diabetes. What are the links between evolution, the environment and a staggering number of people diagnosed with diabetes?

Diabetes is a disease where the body is unable to produce or use insulin effectively. Insulin is needed for proper storage and use of carbohydrates. Without it, blood sugar levels can become too high or too low, resulting in a diabetic emergency. It affects about 7.8% of the population. The incidence of diabetes is known to increase with age. It’s the leading cause of end-stage renal disease in the US, and is the primary cause of blindness and foot and leg amputation. It is known to cause neuropathy in up to 70% of diabetic patients. Individuals with diabetes are twice as likely to develop cardiovascular disease. There are two types of diabetes: Type 1 and Type 2.

The blood glucose level has very limited range for humans to survive and stay healthy. Generally, people are able to remove excess glucose rapidly from the body but this is not the case when they are diagnosed with diabetes and insulin resistant situations. The lack of insulin resistance can also lead to a decrease in glycogen synthesis and storage as it usually converts glucose to energy for cell’s use (Jensen & et al. 2011). When insulin is produced under insulin resistance, the cells are incapable of using them effectively which then leads to high blood sugar level as ketones and ketoacids are produced as an alternative energy source for the body. The rise of ketoacid causes the blood pH acidic and the patient may also be diagnosed with ketoacidosis (Newton & Raskin 2004). There would also be less intake of lipid and more of stored triglycerides as the lipids are effected by the insulin. As the glucose levels increase, the muscle glucose uptake will decrease while the liver glucose production and blood fatty acid concentration will also increase within the body (Lichtenstein & Schwab 2000). Excess glucose within the blood are converted to fat which can lead to Diabetic Dyslipidaemia and furthermore to obesity, hypertension and

Type 2 diabetes mellitus (T2D) is the most common form of diabetes (American Diabetes Association, 2012). T2D is so prevalent that it is estimated to be the fifth most common cause of death worldwide (Yates, Jarvis, Troughton, and JaneDavies, 2009, p. 1). T2D manifests when the body is unable to metabolize glucose properly, resulting in elevated blood sugar, debilitating fatigue, and other serious complications such as distal limb amputations, kidney failure, and blindness. The generally accepted causes of T2D include diet, sedentary lifestyle, and obesity.

The increase in the prevalence of type 2 diabetes is causing huge health problem through out the world including developed countries. Mostly people with low income groups are affected in developed countries (Zimmet 2001).The magnitude of the healthcare problem of type 2 diabetes results mainly from its association with obesity and cardiovascular risk factors. Indeed, type 2 diabetes has now been identified as one manifestation of the “metabolic syndrome”, a condition characterised by insulin resistance and associated with a range of cardiovascular factors (Jonathan 2003)

Diabetes is a growing concern and health challenge for the American people (b). Diabetes is a condition in which the body cannot react to insulin appropriately or either cannot produce insulin efficiently (w). “Without a properly functioning insulin signaling system, blood glucose levels become elevated and other metabolic abnormalities occur, leading to the development of serious, disabling complications” (w). There are numerous forms of diabetes amongst the nation, however, there are three main forms of diabetes. Most people have heard of type one diabetes, type two diabetes, and gestational diabetes because they are common. Type two diabetes deals with a resistance to insulin, while

Superoxide dismutase (SOD) is a free radical scavenging enzyme that catalyses the dismutation of highly reactive superoxide anion O2 to molecular (O2) and to the less reactive species hydrogen peroxide. It has been proposed that poor glycemic control in diabetes is associated with depletion of antioxidant enzymes including SOD.

Type 2 diabetes is a polygenic, complex disease that has become a worldwide health crisis. According to the World Health Organization over 422 million people in the world had this disease in 2014 (1), the Center for Disease Control and Prevention stated that in the United States alone 29 million people had diabetes in 2014 (2). While the genetic predisposition contributing to the diabetes phenotype is not fully understood to date it still remains an area of active research. There are also various environmental factors that contribute stress to the glucose homeostasis system that provide a different approach in understanding this disease. Comprehending the pathogenesis of the disease has been an area of constant research for decades. There is hope that pharmaceutical developments can follow along and find medical treatments that can target the key pathogenic elements of this disease.

Insulin resistance is the first physiological change occurring in type two diabetes. In these type two diabetic patients, insulin is unable to move glucose into liver, kidney and muscle cells although insulin is able to attach properly to the cell surface receptors. In order to rectify this, most patients with type two diabetes start secreting normal to very high levels of insulin, which can initially overcome this resistance. After a while, the pancreas cannot keep up with this high insulin production and the cells become resistant to glucose intake. Persistent hyperglycemia or high blood glucose levels are not desirable since this causes damage to the beta cells of the pancreas that produces the insulin hormone. This damage to beta cells further hampers insulin synthesis and patients at this stage are categorized as full-blown diabetic. Such patients consistently show a hyperglycemia state even after hours of fasting ( Hinkle & Cheever,

Similarly, an increase in the levels of lipid peroxidation was observed in Aβ-induced rat hippocampal cells, confirming previous reports [17]. Enzymatic antioxidants such as SOD, catalase, and GPX act as the cellular antioxidant defense mechanism against free radicals. Since NADPH is required for the regeneration of catalase from its inactive form, catalase activity might be decreased in Aβ induced toxicity due to reduced NADPH levels. In this study, we have reported that Honokiol treatment significantly increased the enzymatic antioxidant activities in APP-CHO cells. In addition, non-enzymatic antioxidants like GSH also exhibited beneficial neuroprotective effects against oxidative stress. GSH is an endogenous nonenzymatic antioxidant that prevents damage to cellular components caused by ROS such as free radicals and peroxides. GSH is oxidized to glutathione disulfide (GSSG) by ROS, thereby causing a reduction in the level of GSH. GR reduces GSSG to GSH via NADPH, which in turn is released by glucose-6-phosphate dehydrogenase [18]. Honokiol treatment upregulated the activity of these antioxidants in APP-CHO cells. In addition to oxidative stress, a strong association between insulin resistance and the development of AD has been demonstrated. Several studies have reported that insulin resistance (IR), an underlying characteristic of type 2 diabetes, is an important risk factor for AD

Diabetes has become a widespread epidemic, primarily because of the increasing prevalence and incidence of type 2 diabetes. Diabetes is an endocrine disease in which the body has either a shortage of insulin or a decrease ability to use insulin or both. Insulin is a hormone that allows glucose to enter the cells and be converted into energy. Diabetes can be characterized as a prevailing, incapacitating, and deadly disease. There are a number of risk factors that increase a person’s tendency toward developing type II diabetes. Modifiable risk factors include obesity, physical inactivity and poor dietary habits are just a few. The

Several possible mechanisms have been explained regarding diabetes induced neurodegeneration. Diabetes mellitus and the accompanying hyperglycemia is a chronic endogenous stressor that is accompanied with increased oxidative stress in brain, particularly the hippocampus, by accelerating free radical generation. These radicals contribute to increased neuronal degeneration by inducing oxidation to proteins, DNA alterations and lipids oxidation in cell membranes .

Oxidative stress is widely accepted to be associated with dysfunction of pancreatic β-cells as well as insulin resistance in type 2 diabetes (Henriksen et al., 2011). Experimental evidences suggest the involvement of free radicals in the onset of diabetes and more importantly in the development of diabetic complications (Lipinsky, 2001). Studies have revealed decreases in expression of genes for antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase, and catalase in diabetic models (Lenzen et al., 1996). Also a decrease in the activities of the antioxidant/ antioxidant enzyme systems in diabetics are linked to the progressive glycation of the enzyme proteins (Hartnet et al., 2000). The interrelationship between the antioxidative potentials and antidiabetic activities of bioactive compounds is still unclear. In the present study, the extent of free radical damage orchestrated by STZ administration was significantly reduced by the antioxidant composition and combination treatment in a dose-dependent manner; thereby reducing the extent of pancreatic β-cell damages among the rats co-treated with combination therapy and STZ, relative to normal and STZ-only rats. The HFD/STZ-induced diabetic control rats had significantly lower (p< 0.05) of total SOD, CAT, GST and GPx activities among the extracts, cell gevity, antioxidant composition and combination therapy co-treated rats (Figure 4.2.34, Figure 4.2.35, Figure 4.2.36, Figure 4.2.37). HFD/STZ decreased the

Type 1 diabetes mellitus (T1DM) is the most common metabolic disorder in which both genetic and environmental factors are involved [1]. T1DM is considered a chronic immune-mediated disorder. It was hypothesized that whilst children have a genetic predisposition to T1DM, there is likely to be an environmental factor that triggers the development of T1DM. Possible triggers that have been suggested include viral infection, vaccines, low levels of vitamin D and cow’s milk, [2]. Oxidative stress is one of the important pathways that have been involved in the etiopathogenesis of T1D [3]. Complications of T1DM could be due to the cellular metabolism leading to hyperglycemia and excess production of reactive oxygen species (ROS).

Diabetes Mellitus is “a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. It is a disease which is caused by the insufficient insulin secretion or decrease in the peripheral effects of insulin. It is a serious problem in terms of morbidity and mortality. The hyperglycemia is associated with long term damage, dysfunction and failure of various organs especially the eyes, kidneys, nerves, heart and blood vessels. It’s associated with many complications which includes blindness of the eyes and amputations of the extremities. It is also associated with neuropathy, retinopathy, and cardiovascular diseases which lead to mortalities.