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A chronic metabolic diseases. Patients often need to take medicine, which costs a lot. Patients often feel thirsty, hungry, and loss weight. The patients were recommended to eat low fat and low sugar food. Diabetes and Polysacchrides Chengxin Sun 2017/5/23 Diabetes Mellitus Disease in which the body doesn’t produce or properly use insulin, lead to hyperglycemia. Main contents Prevalence area and age Diagnosis of DM Symptoms, Effects of Long-term and complications Types of DM Mechanism of DM Drugs of anti-hyperglycimia Polysaccharides Prevalence Virtually no physician is without patients who have the disease Burden of Diabetes The development of diabetes is projected to reach pandemic proportions over the next 10-20 years. International Diabetes Federation (IDF) data indicate that by the year 2025, the number of people affected will reach 333 million, 90% of these people will have Type 2 diabetes. In most western societies, the overall prevalence has reached 4-6%, and is as high as 10-12% among 60-70-year-old people. The annual health costs caused by diabetes and its complications account for around 6-12% of all health-care expenditure. Cost of DM Diagnosis of Diabetes Mellitus Diagnosis of Diabetes Mellitus A1C means a kind of glycosylated hemoglobin Symptoms Diabetes mellitus may present with characteristic symptoms such as thirst, polyuria, blurring of vision, and weight loss. In its most severe forms, in absence of effective treatment, death. Often symptoms are not severe, or may be absent, and consequently hyperglycaemia sufficient to cause pathological and functional changes may be present for a long time before the diagnosis is made. Effects of Long-term The long–term effects of diabetes mellitus include progressive development of the specific complications of blindness, renal failure, foot ulcers, and features of autonomic dysfunction, including sexual dysfunction. Types type 1 diabetes type 2 diabetes gestational diabetes mellitus (GDM) other specific types of diabetes Type 1 diabetes It was called insulin-dependent diabetes mellitus (IDDM) previously. Type 1 diabetes develops when the body’s immune system destroys pancreatic beta cells, the only cells in the body that make the hormone insulin that regulates blood glucose. This form of diabetes usually strikes children and young adults, although disease onset can occur at any age. Type 1 diabetes may account for 5% to 10% of all diagnosed cases of diabetes. Risk factors for type 1 diabetes may include autoimmune, genetic, and environmental factors. Type 2 diabetes It was previously called non-insulin-dependent diabetes mellitus (NIDDM). Type 2 diabetes may account for about 90% to 95% of all diagnosed cases of diabetes. It usually begins as insulin resistance, a disorder in which the cells do not use insulin properly. As the need for insulin rises, the pancreas gradually loses its ability to produce insulin. Type 2 diabetes is associated with older age, obesity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity. African Americans, Hispanic/Latino Americans, American Indians, and some Asian Americans and Native Hawaiians or Other Pacific Islanders are at particularly high risk for type 2 diabetes. Type 2 diabetes is increasingly being diagnosed in children and adolescents. Gestational diabetes A form of glucose intolerance that is diagnosed in some women during pregnancy. During pregnancy, gestational diabetes requires treatment to normalize maternal blood glucose levels to avoid complications in the infant. After pregnancy, 5% to 10% of women with gestational diabetes are found to have type 2 diabetes. Women who have had gestational diabetes have a 20% to 50% chance of developing diabetes in the next 5-10 years. Other types of DM Other specific types of diabetes result from specific genetic conditions (such as maturity-onset diabetes of youth), surgery, drugs, malnutrition, infections, and other illnesses. Such types of diabetes may account for 1% to 5% of all diagnosed cases of diabetes. What goes wrong in diabetes? Multitude of mechanisms Insulin Regulation Secretion Uptake or breakdown Beta cells damage Normal state Insulin Secretion Pathological state---Organic model Cellular mechanisms Phosphorylation and dephosphorylation of IRS proteins Adiponectin NFκB and IKK activity Mitochondrial metabolism β-cell dysfunction +P and -P of IRS proteins Phosphotyrosine phosphatase 1B (PTP1B) is widely expressed and negatively regulate insulin signalling. Serine/threonine phosphorylation of IRS1 reduces its ability to act as a substrate for the tyrosine kinase activity of the insulin receptor and inhibits its coupling to its major downstream effector systems. adipocyte Adiponectin signals via AMP kinase, a stressactivated signalling enzyme implicated in various metabolic responses, including suppression of hepatic gluconeogenesis, glucose uptake in exercising skeletal muscle, fatty acid oxidation, and inhibition of lipolysis, which might explain its beneficial metabolic effects AMP kinase has also been implicated in the mechanism of action of metformin, and possibly of the thiazolidinediones, suggesting that it has a role in clinical anti-diabetic responses. NFκB and IKK activity Nuclear factor κB (NFκB) is held in an inactive state in resting conditions by binding to an inhibitory partner, Phosphorylation of IκB by its kinase (IKK) leads to IκB degradation, releasing NFκB for translocation to the nucleus where it can affect the transcription of diverse genes involved in the inflammatory response. NFκB and IKK activity IKK NFκB - IκB NFκB IκB Gene transcription +Insulin resistance Mitochondrial metabolism mitochondrial lipid oxidation in patients who have impaired oxidative capacity and small mitochondria in skeletal muscle. PPARγ co-activator 1 (PGC1), a transcription factor for genes involved in mitochondrial fatty acid oxidation and ATP synthesis, was decreased in young, lean, insulinresistant offspring of parents with type 2 diabetes, suggesting that an inherited defect in mitochondrial oxidative phosphorylation could lead to cellular lipid accumulation. Decreased expression of PGC1 and related gene products could affect mitochondrial function in people with insulinresistance β-cell dysfunction Glucose toxicity Lipotoxicity Islet amyloid Cellular model Glucose toxicity In β cells, oxidative glucose metabolism will always lead to production of reactive oxygen species, normally detoxified by catalase and superoxide dismutase. β cells are equipped with a low amount of these proteins and also of the redox-regulating enzyme glutathione peroxidase. Hyperglycaemia has been proposed to lead to large amounts of reactive oxygen species in β cells, with subsequent damage to cellular components. Loss of pancreas duodenum homeobox 1 (PDX-1), a critical regulator of insulin promoter activity, has also been proposed as an important mechanism leading to βcell dysfunction. Additionally, reactive oxygen species are known to enhance NFκB activity, which potentially induces β-cell apoptosis. Lipotoxicity in both non-diabetic and diabetic obese patients, NEFA(“non-esterified fatty acid” or “free fatty acid”) concentrations are raised as a result of enhanced adipocyte lipolysis. Fatty acids lead to enhanced insulin secretion in acute studies, but after 24 h they actually inhibit insulin secretion. In the presence of glucose, fatty acid oxidation in β cells is inhibited and accumulation of long-chain acyl coenzyme-A occurs. However, long-chain acyl coenzyme A itself can also diminish the insulin secretory process by opening β-cell potassium channels. A second mechanism might be increased expression of uncoupling protein-2, which would lead to reduced ATP formation and, hence, decreased insulin secretion. A third mechanism might involve apoptosis of β cells, possibly via fatty acid or triglyceride-induced generation of nitric oxide. Islet amyloid Islet amyloid consists of deposits of islet amyloid polypeptide, also known as amylin, which is co-secreted with insulin at a more than tenfold lower rate. The physiological role of islet amyloid polypeptide is unclear, and diverse roles such as inhibition of insulin action, inhibition of insulin secretion, and inhibition of glucagon secretion have been proposed. It has been suggested that small aggregates are cytotoxic, possibly related to radical production. Melecular model Drug of antihyperglycaemia Thiazolidinediones Metformin α-glucosidase inhibitors Sulfonylurea derivatives Exogenous insulin Glucagon-like peptide 1 Experimental approaches Summary drugs Polysaccharides Polysaccharides belong to a structurally diverse and complex class of macromolecules, in which many monosaccharides joined together by glycosidic linkages. They are abound in nature products, especially in plant medicines. They are commonly extracted from nature products by hot water, and can be further purified using a combination of techniques, such as ethanol precipitation, fractional precipitation, and acidic precipitation with acetic acid, ionexchange chromatography, gel filtration, and affinity chromatography. Over 100 polysaccharides from plants have been reported for hypoglycemic activity. Some botanical polysaccharides are considered as important bioactive components responsible for hypoglycemic effect. Investigations showed this polysaccharide administered orally can significantly reduce blood glucose levels and water intake, and increase the body weight of diabetic mice compared with alloxan-induced diabetic control group. 多糖产品 Main antiDM polysaccharides Astragalus polysaccharides Lycium barbarum polysaccharides Tea polysaccharides Panax Ginseng polysaccharides Ganoderma lucidum polysaccharides Momordica charantia polysaccharides Lycium barbarum 枸杞 Astragalus 黄芪 Ganoderma lucidum 灵芝 Ginseng 人参 Why and How are left for us to investigate Referrence 1 Qi, L. W. et al. Anti-diabetic agents from natural products - An update from 2004 to 2009. Current Topics in Medicinal Chemistry 10, 434-457, doi:10.2174/156802610790980620 (2010 ). 2 Standards of medical care in diabetes-2010. Diabetes Care 33 (2010). 3 Dall, T. et al. Economic costs of diabetes in the U.S. in 2007. Diabetes Care 31, 596-615 (2008). 4 Stumvoll, M., Goldstein, B. J. & van Haeften, T. W. Type 2 diabetes: principles of pathogenesis and therapy. The Lancet 365, 1333-1346, doi:Doi: 10.1016/s0140-6736(05)61032-x (2005). 5 http://www.diabetesatlas.org/ 6 http://www.healthypeople.gov/ Welcome to China Welcome to NENU (Northeast Nromal University) Thank you! Email: [email protected] Keep on going and never give up, then someday you will succeed!