„Insulin“ history uBanting and Best – 1921 – described insulin (as the islet hormones was named) u(an aqueous extracts of pancreas couls be lower blood glucose and prolong survival in a pancreatectomized dogs in experiment – laboratory in Department of Physiology, University of Toronto, Canada) uEnd of 1923 insulin was being prepared from beef and pork pankreas on an industrial scale – patients from around the world were receiving effective treatment of their diabetes u1924 Nobel price: Banting and MacLeod Beta cells of pancreas secrete: uInsulin uProinsulin uC peptide uAmylin (new described protein, 37 aminoacid peptide co-secreted with insulin. It delays gastric emptying, suppresses post-prandial glucagon secretion, increases satiety) u uAlfa cells principally secrete glucagon uDelta cells – somatostatin uF cells – pancreatic polypeptide u Boron and Boulpaep, Medical Physiology, 2003 Effects of insulin Carbohydrates promotes glucose entry into cells Ý synthesis of glycogen inhibits glycogenolysis inhibits gluconeogenesis Lipids promotes lipids synthesis inhibits lipolysis in adipose and muscle cells proteins promotes amino acid entry into liver, muscle and adipose cells has a direct effect on the ribosomes in increasing the translation of messenger RNA, thus forming a new proteins (inhibits the catabolism of proteins) Effects of insulin Carbohydrates promotes glucose entry into cells Ý synthesis of glycogen inhibits glycogenolysis inhibits gluconeogenesis Lipids promotes lipids synthesis inhibits lipolysis in adipose and muscle cells proteins promotes amino acid entry into liver, muscle and adipose cells has a direct effect on the ribosomes in increasing the translation of messenger RNA, thus forming a new proteins (inhibits the catabolism of proteins) proinzulin inzulin C-peptid S S S S S S A řetěz B řetěz S S S S S S Zn Golgiho aparát / Golgi Apparatus Golgi vesicles / granula Zn2+ Beta cell hexamer - inzulinu Endogenous insulin is formed by the cleavage of proinsulin to insulin and C peptid. If a patient experiences hypoglycaemia in the presence of high insulin levels, C peptide measurements help to distinguish between excess endogenous insulin (e.g. insulinoma) and excess exogenous insulin (e.g.overdose). proinzulin inzulin C-peptid S S S S S S A řetěz B řetěz S S S S S S Zn Zn2+ beta cell hexamer - inzulinu -Ý perfusion -- Ý difusion in capillary region -- Ý intake of oxygen and glucose into the cells half-time decomposition: 25 min IR I apochromodulin Vincent J. B.: J. Nutr. 130: 715 – 718, 2000 IR I apochromodulin transferin-Cr Cr3+ IR I chromodulin IR I chromodulin chromodulin Decrease concentration of insulin insulin-sensitive cells IR I apochromodulin : glycaemia glucagon catecholamins glucocorticoids STH (growth hormon) insulin Insulin secretion STIMULATION by - glucose amino acids fatty acids ketone bodies acetylcholin Gastrointestinal peptid -GIP secretin gastrin GLP 1 INHIBITION by - insulin noradrenalin adrenalin alfa2-stimulation hyperglycaemia somatostatin chronic hyperglycaemia Secretion of glucagon Stimulated by hypoglycemia aminoacid acetylcholin epinephrin Inhibited by insulin fatty acid somatostatin DIABETES MELLITUS u„Epidemic of the 21st century“ u u„Chronic progressive disease“ u„Vessels - vascular disease“ Diabetes is the common term for several metabolic disorders in which the body no longer produces insulin or uses the insulin it produces ineffectively. It is a common condition and is characterised by abnormally high blood sugar levels. Diabetes is known as "diabetes mellitus" - where diabetes comes from the Greek word for siphon, which describes the excessive thirst and urination of this condition, and mellitus is the Latin word for honey, because diabetic urine is filled with sugar and is sweet. The key to the problem is insulin - as insulin's role in the body is to help glucose get into the body cells where it is used to make energy. Diabetes is characterized by a partial or complete lack of insulin production by the body. The most common forms of diabetes are: Prediabetes – increase glycemia morning, oGTT disapear Type 1 diabetes Type 2 diabetes ( In both types of diabetes, people have little or no ability to move sugar out of the blood stream and into the cells, where it is used as the body's primary fuel) DIABETES MELLITUS - incidence worldwide Czech Republic – year: 2000 – 654 000….year: 2013 - 861 000, new patients with DM - 72 600 during 13 years ☺ promising field in your decision for the future ☺ as good job ♡ USA – 320 million people – 30 million have diabetes 100 million do not know their illness - prediabetes!!!!! Healthy people Diabetes mellitus 1 Diabetes mellitus 2 insulin secretion without insulin secretion ß insulin secretion (resistence) ß receptors:down regulation or Type 1 diabetes develops when an "autoimmune reaction" destroys beta cells in the pancreas. Autoimmune reaction means that the body creates antibodies against its own cells. As a result, the pancreas stops producing insulin or cannot produce enough insulin on its own. Treatment involves daily insulin injections, in conjunction with healthy eating and regular exercise. Type 1 diabetes most often affects people under 20 years of age. It was previously called juvenile-onset diabetes or Insulin-Dependent Diabetes Mellitus (IDDM). polyuria (excessive elimination of urine - frequent urination) polydipsia (excessive drinking of water-extreme thirst and/or hunger) weight loss fatigue •An acetone-like smell around the body •Fatigue, weakness, drowsiness Clinical specialities of DM type 1 reccurents infections metabolic syndrom Risk factors of type 2 diabetes include: •Age (being over 45 years old) •Being overweight or obese •Having a family history of diabetes •Ethnic background or race (Native/Indigenous, African, Hispanic or Asian descent) •Having given birth to a large baby (over 4 kg or 9 lbs) •Impaired glucose intolerance The symptoms of type 2 diabetes are the same as type 1 diabetes. Some people may also experience slow healing cuts and bruises, recurring gum or bladder infections, or tingling in their hands or feet. Other terms previously used for type 2 diabetes are adult-onset diabetes and Non-Insulin Dependent Diabetes Mellitus (NIDDM). DM 2 Artery damage: diabetic retinopathy (among adults, diabetes is the leading causes of blindness) hypertension stroke myocardial infarction diabetic nephropathy (kidney disease - failure) Nerve damage: diabetic neuropathy Risk factors in patients with DM acute hypoglycemia < 3,3 mmol/l sweat, starvation, vertigo, headache, heart palpitation, tremor, double vission, tiredness, sleepiness, spasmus, unconsciousness hyperglycemia > 15 mmol/l be thirsty, starvation, sleeepiness, spasm in down extremities, unconsciousness Complication of DM chronic specific retinopathy, neuropathy, nephropathy non specific atherosclerosis mortality cardiovascular diseases Complication of DM „ The Incretin effect“ uDesignates the amplification of insulin secretion elicited by hormones secreted from the gastrointestinal tract. u uIn healthy subject the oral administration of glucose causes two- to threefold larger insulin response than the intravenous route as a results of the actions of the incretin hormones: u u glucose dependent insulinotropic polypeptide (GIP-previously named as gastric inhibitory polypeptid) uGlucagon like peptid 1 (GLP 1) u sulfonylureas uEnhance insulin secretion by beta cells by binding to and inhibiting ATP-sensitive K+channels, thereby decreasing the likelihood that these channels will be open. This action enhances glucose-stimulated insulin secretion (a proces in which this same channels is responsible for cell depolarization) uBy increasing insulin secretion and decreasing blood glucose-decresed the insulin resistance Ensure correct site of injection: Abdomen for fast acting insuling and thigh or buttock for prolonged acting insulin. Rotate injection sites within a given body region. How to inject? The goal is to ensure injection in the subcutaneous tissue layer (the fatty layer located immediately under the skin). Pinch up the skin between two fingers to form a lifted skin-fold, rotate gently to ensure that the underlying muscle is not also raised in the skin-fold. Insert the needle at a 90 degree angle to the lifted skin-fold. Inject smoothly and leave under the skin for at least 6 seconds after the injection is complete. C:\Documents and Settings\ja\Plocha\LargeSpot_NovopenJunior_NHCP.jpg uinjection devices, with a range of designs and features. New devices use very thin needles and are virtually painless. They are easy, simple and convenient to use. Hypoglycaemia – mild, moderate or severe type uA hypo is a short term for hypoglycaemia which means low blood glucose. It can cause a wide spectrum of unpleasant symptoms, and if severe enough can lead to unconsciousness, coma or death. uHypos feel differently from person to person. u uSymptoms and signs uAnxiety Blurred Vision Feeling cold uFeeling weak Drowsiness Euphoria uHeadache Hunger Irritability uNervousness Pounding heart Restless sleep uSweating Trembling Unconsciousness u u