[MUSIC] Hello, everyone. Welcome back to my Coursera class, Biochemical Principles of Energy Metabolism. This is session four, week six. This session and following session. Sessions four and five are about diabetes. One of the major metabolic disturbances related to biogenics. So let's begin with the definition of diabetes. Diabetes mellitus, so-called DM and this is simply referred to as diabetes. So this is a group of metabolic diseases in particular, associated with the chronic high blood glucose levels. This blood glucose level, high levels of blood glucose maintained for long time chronically. This is diabetes mellitus. The symptoms, frequent urination and increased thirst and hunger. And this metabolic disease, the main reason for why this disease is such a devastating one. Because many medical complications are associated with diabetes mellitus. So diabetic ketoacidosis and diabetic retinopathy, that means this cause finally blindness. And then many cardiovascular problems and even stroke and the kidney failure or in severe cases coma, or even death in particular diabetic ketoacidosis. And in many terminal stage of diabetes, patients they lose limb structure, foot, or hands and fingers. Because of the high levels of blood sugar that results in the glucose toxicity of many neurons and peripheral tissues are not happy. Simply speaking, they cannot survive of those high blood glucose levels. There is a biochemical and cell biological like problems of toxicity, so-called glucotoxicity. High levels of glucose can be very, very toxic to peripheral tissues and cells. So this diagram is showing the main symptoms of diabetes. Eye problems, brain and the cardiovascular problems and respiratory, urination is really a devastating disease. So let me further introduce the importance of diabetes and it's time to classify. So diabetes develops in two cases, mainly. Number one is when your body cannot synthesize enough insulin or your cells, when they cannot respond appropriately to the insulin. There are two cases, number one and number two. So as of 2015, estimated roughly 415 million people suffering from the diabetes and particular type two diabetes. I'm going to explain type two diabetes is global cost diabetes in 2014 is just estimated US $612 billion. It's a really, really devastating disease and this disease cost a lot of money for the treatment and management. There are two, types type one and type two. Type one is pancreatic beta cells cannot produce enough insulin. In many cases, this is like autoimmune based. So the patients own cells, immune cells can attack and destroy pancreatic beta cells. So you have insulin connectors secreted, cannot be made and secreted. So extra insulin supposed to be supplied through the injections and the type two is the most common type of diabetes mellitus. This is associated with very, very important medical condition. Insulin resistance, which is defined by like this. Peripheral cells, they cannot properly respond to insulin. Insulin resistance associated with type two diabetes, the most common type and the main factors to drive this type two diabetes is nutrient overload and obesity and modern lifestyle like lack of exercise. More simply, we just sit on the chair for a long time in our lifestyle in the modern society. Drive this, the onset of type two two diabetes and the third case is a little bit unique. Pregnant women can have gestational diabetes. Roughly 2 to 10% of pregnant women actually are suffering from the high blood glucose level. And in many cases, after delivery. I mean, when they deliver their babies and then the symptoms in many cases are reduced. So the total estimated death related to type two diabetes and even type one diabetes mellitus in 2012, one example per million persons. This is heat map, many areas actually in the world. The diabetes mellitus can lead to the severe death. We have to care about the management and treatment of this disease, metabolic disease. So I'm going to focus on type two diabetes. Because type one diabetes, the cause is very clear. The pancreatic beta cells, genetically that they cannot properly developed or through out this autoimmune condition pancreatic beta cells are destroyed. So synthesis of insulin can be blocked. In type two diabetes is associated with insulin resistance. So insulin receptor signaling, we studied about this in the previous session. Actually, impaired peripheral tissues. Even though insulin levels are okay in the very beginning, but peripheral tissues, the insulin receptor and downstream signaling cannot properly trigger the glucose uptake and relate it on insulin remediated by a chemical event. So these target cells are insulin resistant and this is the main situation, strongly and highly linked to type two diabetes. So insulin resistance as I said, a pathological condition in which the peripheral cells cannot properly respond to insulin hormone. So in this case, pancreatic beta cells, they can't, even though, I mean, beta cells can secrete insulin in the very beginning like a regular situation. The thing is peripheral cells, they become resistant to the insulin. So in that case, glucose uptake will be inhibited. It's not going to be normal. So high levels of blood glucose can be manifested. And during this initial stage, pancreatic beta cells, they are quite active in producing more insulin. Because peripheral tissues, their insulin sensitivity is not that good. So right up pancreatic beta cells, they're trying to synthesized and produce more insulin. However, under the chronic insulin resistance situation. Finally, pancreatic beta cells too much stressed out about the huge amount of insulin secretion and they become malfunctional in the later stage of type two diabetes. So finally, pancreatic beta cells becomes the failure state. So the thing is the people who are eventually developing type two diabetes, actually, the only stage of insulin resistance symptoms and prediabetic symptoms cannot be clearly diagnosed. This is one of main concerns in the treatment of type two diabetic patients.
