The rough endoplasmic reticulum (ER) is the site of synthesis for many proteins in the cell. It also assists in the subsequent protein folding via numerous proteins housed in its lumen. However, the rough ER can be subjected to stress and protein folding may not always be completed or properly executed. ER stress leading to an accumulation of both unfolded and misfolded proteins triggers the unfolded protein response, or UPR. The UPR is a mechanism by which the ER increases its protein folding capacity and decreases its client load, thus enabling it to cope with the stress. However, extended periods of UPR activation due to extreme and prolonged ER stress harms the cell. Correlational and mechanistic research studies have shown that sustained UPR contributes to the pathogenesis of Type II Diabetes—a disorder characterized by raised blood sugar levels due to insulin resistance. Obesity, the most common cause of type II Diabetes, causes ER stress that triggers two UPR signal transduction pathways—the Inositol requiring protein–1 (IRE1) and protein kinase RNA-like ER kinase (PERK) pathways. IRE1 leads to insulin resistance by inactivating an adaptor protein needed for insulin’s interaction with its receptor. PERK amplifies elevated blood sugar levels by activating an apoptotic agent that targets the insulin-producing beta cells of the pancreas. Currently, various medical treatments for Type II Diabetes are being pursued. This includes non-peptide insulin action enhancers, incretins and glucokinase activators.
Type II Diabetes
Insulin is a hormone produced by the pancreas in response to high blood sugar levels (Vijan, 2010). It stimulates cells to uptake glucose, where it can either be metabolized for energy or stored as glycogen (e...
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...cokinase activation also lowers blood glucose by promoting glycogen synthesis in the liver (Pal, 2009).
In conclusion, Type II Diabetes is mediated by prolonging the endoplasmic reticulum’s unfolded protein response, or UPR (Ozcan and Tabas, 2012). Obesity subjects the ER to extreme stress which triggers excessive activation of both the IRE1 and PERK signalling pathways of the UPR (Wu and Kaufman, 2006). These lead to insulin resistance, as well as death of pancreatic cells that produce insulin, respectively (Ozcan and Tabas, 2012). Various treatments are now being used to address Type II Diabetes. This includes TLK16998-based drugs that enhance insulin action, intestinal GLP-1 incretins that increase insulin and supress glucagon, and glucokinase activators that upregulate insulin secretion and promote glucose storage in the form of glycogen (Tahrani et al., 2011).
This is monitored by the cells within the Islets of Langerhans, which is located in the control (the pancreas). After skipping a meal or tough physical exercise blood glucose concentration decreases. Alpha cells in the islets detect this drop and are stimulated to secrete glucagon. Glucagon is a polypeptide hormone which influences an increase in blood glucose concentration. Glucagon travels through the bloodstream until it reaches glucagon receptors which are predominantly found in the liver, as well as, the kidneys. Glucagon stimulates the breakdown of stored glycogen to be released into the bloodstream as glucose. It also stimulates the conversion of amino acids into glucose and the breakdown of fat into fatty acids. These effectors cause an increase in blood glucose levels back towards the normal. This increase in blood glucose concentration is detected by the alpha cells which then stop the secretion of
Our body obtains the energy by digesting the carbohydrates into glucose. Volumes of glucose are required by the body to create ATP. ATP is short for 'Adenosine Triphosphate ' and is an energy carrier. When we consume too many carbohydrates our body produces a lot of glucose and as a result blood glucose levels rise and sometimes they may rise over the normal range of blood glucose concentration. To bring it back within the healthy range, the homeostatic system of blood glucose regulation is used. The blood flows through the pancreas where the beta cells, receptors, detect the high blood glucose level. To counteract this stimuli beta cells alert the control centre, which are also the beta cells located in the islets of Langerhans in the pancreas. The secretion of insulin has to be done quickly but can only be carried out when insulin gene is switched on. Turning on the insulin gene switch can take 30 minutes to an hour therefore, the production of insulin by beta cells are done in advance and are packaged in vesicles right until blood glucose rises. Glucose comes into the beta cell to trigger the vesicle that contains the insulin to move towards the plasma membrane and fuse. This releases the insulin into the bloodstream where they are distributed throughout the body and only affect specific target cells. The receptor, a protein, on the target cell’s plasma membrane recognises and connects
Insulin: a hormone made by the pancreas that allows your body to use sugar (glucose) from carbohydrates in the food that you eat for energy or to store glucose for future use. Insulin helps keeps your blood sugar level from getting too high (hyperglycemia) or too low (hypoglycemia). Before insulin Diabetes mellitus was a chronic disease that affected thousands of people in Canada and beyond. In the first half of the 20th century, medical professionals understood that diabetes mellitus involved the body’s inability to metabolize food, especially carbohydrates. “Insuline” was already in development as many medical professionals like Joseph Freiherr and Oscar Minkowski, isolated its properties before Banting had his ideas. As well Ancient Greek
The pathophysiology of diabetes mellitus in is related to the insulin hormone. Insulin is secreted by cells in the pancreas and is responsible for regulating the level of glucose in the bloodstream. It also aids the body in breaking down the glucose to be used as energy. When someone suffers from diabetes, however, the body does not break down the glucose in the blood as a result of abnormal insulin metabolism. When there are elevated levels of glucose in the blood, it is known as hyperglycemia. If the levels continue to remain high over an extended period of time, damage can be done to the kidneys, cardiovascular systems; you can get eye disorders, or even cause nerve damage. When the glucose levels are low in one’s body, it is called hypoglycemia. A person begins to feel very jittery, and possibly dizzy. If that occurs over a period of time, the person can possibly faint. Diabetes mellitus occurs in three different forms - type 1, type 2, and gestational.
Diabetes Mellitus is a disease of the endocrine system primarily differentiated between type 1 and type 2. Type 1 diabetes occurs when the pancreas is unable to produce insulin and was previously seen in the younger generation which is no longer the case.1 Type 2 diabetes is the more prevalent of the two types and involves elevated blood sugar levels due to the insufficient production of insulin. Risk factors that make an individual higher risk for type 2 diabetes include increasing age, obesity, family history, a sedentary lifestyle.1,2 Innovative drug therapies for type 2 diabetes remain important for the treatment and reduction of the disease.
Frequent urination results from the body trying to excrete the excess glucose and thirst follows as dehydration sets in. Hunger, fatigue, mental fogginess, irritability, and mood changes result from a deficiency in ATP as the body cannot produce enough purely through fat metabolism via ketones. Acetone breath quickly follows as the body starts to upregulate fat metabolism in an attempt to use ketones for ATP production. This metabolic pathway creates various ketones, but one ketone acetone, is toxic and is excreted via the lungs. It can be detected as a “fruity” odor in the breath. This upregulation of fat metabolism creates a crisis known as diabetic ketoacidosis which can lead to a coma or even death (Harvey, 2012). Another life threatening acute symptom which is not as common in type 1 as type 2 diabetes is hyperglycemic hyperosmolar nonketonic syndrome or HHNS which can result in serious consequences such as a coma or even death. It is caused by increasing blood sugar and dehydration without the presence of ketones (Harvey, 2012). It can be caused by severe infection, severe illness, and medications that reduce glucose tolerance and increase fluid loss (Harvey, 2012). The various acute symptoms of type 1 diabetes are just as deadly as the long term effects of poor blood sugar
Diabetes is a disease in which a person’s body in unable to make or utilize insulin properly which affects blood sugar levels. Insulin is a hormone that is produced in the pancreas, which helps to regulate glucose (sugar) levels, break down carbohydrates and fats, and is essential to produce the body’s energy. The CDC (2013) offers reliable insight, summarized here, into the different types of diabetes, some causes, and health complications that may arise from the disease.
Insulin is a hormone produced by the B cells in the islets of Langerhans of the pancreas. Under normal conditions, insulin is continuously released into the bloodstream in small pulsatile increments (a basal rate), with increased release (bolus) when food is ingested. The activity of released insulin lowers blood glucose and facilitates a stable, normal glucose range of approximately 70 to 120 mg/dl. The average amount of insulin secreted daily by and adult is approx. 40 to 50 U, or 0.6 U/kg of body weight.
In order for the body to maintain homeostatic levels of energy, blood glucose regulation is essential. Glucose is one of the body’s principal fuels. It is an energy-rich monosaccharide sugar that is broken down in our cells to produce adenosine triphosphate. In the small intestine, glucose is absorbed into the blood and travels to the liver via the hepatic portal vein. The hepatocytes absorb much of the glucose and convert it into glycogen, an insoluble polymer of glucose. Glycogen, which is stored in the liver and skeletal muscles, can easily be reconverted into glucose when blood-glucose levels fall. All of the body’s cells need to make energy but most can use other fuels such as lipids. Neurons; however, rely almost exclusively on glucose for their energy. This is why the maintenance of blood-glucose levels is essential for the proper functioning of the nervous system.
Insulin is a hormone in the body that is critical in many of the body’s functions. Insulin is a hormone made up of a small polypeptide protein that is secreted by the pancreas it affects carbohydrate, protein, and fat metabolism. Your body breaks these nutrients down into sugar molecules, amino acid molecules, and lipid molecules. The body can also store and reassemble these molecules into more complex forms. Insulin causes the storage of these nutrients. After eating a meal blood sugars rise rapidly especially after eating carbohydrates, this signals the release of insulin. Insulin binds to insulin receptors on the outside of cells to open up channels for glucose to move into the cell for storage by the means of GLUT-4 inside the cell. With insulin resistance the pancreas has to work harder to make up for the insulin resistance but as the resistance gets worse the pancreas can not keep up and blood glucose levels stay elevated. A major way to prevent type II diabetes and high blood glucose is to improve a patient’s insulin sensitivity.
Diabetes is a chronic disorder of metabolism characterized by a partial or complete deficiency of the hormone insulin. With this, there are metabolic adjustments that occur everywhere in the body. Specific to this child is Type One Diabetes. This is characterized by demolition of the pancreatic beta cells, which produce insulin. Because of this, it leads to complete insulin deficiency. Within Type One diabetes, there are two different forms. First there is immune-mediated deficiency, which typically results from an autoimmune destruction of the beta cells. The second type is called idiopathic type one, in which the cause is unknown. (Wong, Hockenberry, Wilson, 2015)
Carbohydrates, mainly glucose, are an important source of energy for living organisms. Some tissues of the body (e.g., brain) need a continuous delivery of glucose. Maintenance of blood glucose concentrations within a normal range is critical to the regulation of normal fuel use by the organs. This is primarily accomplished by the two hormones, Insulin and Glucagon, which are secreted by the alpha and beta cells of the pancreas, respectively. The function of Insulin is to keep the blood glucose in check by helping it to move inside the cells of our body, thereby decreasing its concentration in the blood. Glucagon does exactly the opposite. Other hormones of our body like glucocorticoids, epinephrine and the growth hormone also function like Glucagon.
It was expected that the participants who ingested glucose and rested, to have their blood sugars elevate and slowly return to the normal range. Blood sugars will rise because the glucose isn’t being used, the glucose stays stored and makes blood glucose levels elevate.
The pancreas, in addition to its digestive process has two important hormones, Insulin and Glucagon which are important for the maintenance of blood glucose level at a narrow range. Not only glucose, but also they are important for protein and lipid metabolism. Glucagon is secreted by the alpha cells of the islet of Langerhans and Insulin is secreted by the beta cells of Langerhans. Both are secreted to portal vein. (8)
Diabetes mellitus (DM) or simply diabetes, is a chronic health condition in which the body either fails to produce the amount of insulin needed or it responds inadequately to the insulin secreted by the pancreas. The three primary types of diabetes are: Diabetes Type 1 and 2, and during some pregnancies, Gestational diabetes. The cliché for all three types of diabetes is high glucose blood levels or hyperglycemia. The pathophysiology of all types of diabetes mellitus is related to the hormone insulin, which is secreted by the beta cells of the pancreas. This hormone is responsible for maintaining an optimal glucose level in the blood. It allows the body cells to use glucose as a main energy source. Due to abnormal insulin metabolism, in a diabetic person, the body cells and tissues cannot make use of glucose from the blood, resulting in elevated blood glucose level or hyperglycemia. Over time, elevated blood glucose level in the bloodstream can lead to severe complications, such as disorders of the eyes, cardiovascular diseases, kidney damage and nerve destruction. In Type 1 diabetes, the pancreas is not able to produce sufficient amount of insulin as required for the body. The pathophysiology of type 1 diabetes suggests that it’s an autoimmune disease, in which the body’s own immune system generates secretions of substances that attack the beta cells of the pancreas leading to low or no insulin secretion. This is more common in children and young adults before the age of thirty. Type 1 is also referred as Insulin dependent Diabetes Mellitus or Juvenile Diabetes, exogenous insulin is needed for its treatment. In type 2 diabetes mellitus we find insulin resistance with varying degrees of insulin secretory defects and is more comm...