内分泌生殖系统教学课件：07 胰岛素和血糖调控.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Insulin and the regulation of plasma glucose,Part 1 Introduction,Circulating glucose level are maintained,within tight limits,which requires a complex control system.,Importance of Glucose Regulation,Too little,Brain problems,Too much,Osmotic water loss(cellular and systemic),Damages blood vessels,fluorodeoxyglucose-positron-emission tomography,FDG-PET,Glucose in urine,Anatomy of the pancreas,The functions of pancreas,1.,Exocrine function:pancreatic juice,2.Endocrine function:hormones,The endocrine pancreas,胰岛激素与血糖,（）,（）,Hormones of endocrine pancreas,Part 2 Insulin and the response to high blood glucose levels,Insulin discovered byFrederick Banting and Charles Best in 1921.,Leonard Thompson first patient successfully treated.,1965/9/17,it is the first protein synthesized by,Chinese,scientists.,Before and after receiving insulin(McCormick),Leonard Thompson(19081935),51 amino acids,2 chains linked by disulfide bonds,5800 Dalton molecular weight,Synthesis and secretion,Insulin in blood,1.No specific carrier,2.Half life:3-5 min,3.Normal fasting level is within a tight range,4.Changed in response to food intake.,Effects of Insulin,Nearly all cells(80%)increase glucose uptake(seconds),Active transport,Primarily affects liver and muscle,Brain tissue is excepted,Alters phosphorylation of many key intracellular metabolic enzymes(minutes),Alters protein synthesis and gene transcription(hours),Insulin Affects Tissues Differently,Muscle,Uptake of glucose and immediate use(exercise)or storage as glycogen(Exercising muscles can take up glucose without insulin),Inhibits glycogen breakdown,Liver,Uptake of glucose and storage as glycogen.,Inhibits glycogen breakdown,Inhibits gluconeogenesis.,Adipose Tissue,Promotes glucose uptake and conversion to glycerol for fat production,Insulin and Fat Metabolism,Liver cells store glycogen only up to 5-6%,Remaining glucose metabolized to fat,Triglycerides are synthesized and release into blood,Inhibits breakdown of fatty acids to ketones.,Adipose cells store fat,Inhibits breakdown of triglycerides,Stimulates uptake and use of glucose to form glycerol,Stimulates fatty acid uptake and conversion to triglycerides,Lack of insulin,Free fatty acids build up in blood,Liver metabolizes to produce phospholipids and cholesterol,Can lead to excess acetoacetic acid production and buildup of acetone(acidosis,which can lead to blindness and coma),Insulin and Protein Metabolism,Promotes,Transport of amino acids,Protein synthesis,Gene transcription,Inhibits protein degradation,Prevents glucose synthesis in liver,Inhibits breakdown of amino acids to form glucose.,Decreases urea formation,Lack of insulin causes elimination of protein stores,Insulin Control,Muscle,Glucose uptake,Glycogen synthesis,Liver,Glucose uptake,Glycogen synthesis,Fatty acid synthesis,Glucose synthesis,Brain,No effect,Pancreas,Beta cells,Gastrointestinal,hormones,Feedback,amino,acids,glucose,triglycerides,Adipose,Glucose uptake,Glycerol production,Triglyceride breakdown,Triglyceride synthesis,Insulin,Most Cells,Protein synthesis,Amino acids,Bloodglucose,Regulation of insulin secretion,1.Plasma glucose concentration,2.Others:Ach,bombesin,GLP1,Part 3 Hormones that act to raise blood glucose levels,Glucagon,Other hormones,1.,cell,2.29-amino-acid peptide,3.Response to low glucose levels,4.Effects:on liver,blood glucose,(1)Increase glycogenolysis,(2)Stimulate gluconeogenesis,(3)stimulate lipolysis,(4)cell uptake Glu and amino,Glycolysis,Glucagon,Glucagon Control,Liver,Glycogen breakdown,Glucose synthesis,Glucose release,Brain,No effect,Pancreas,Alpha cells,Exercise,Feedback,Adipose,Triglyceride breakdown,Triglyceride storage,Blood,glucose,Fatty acids,Epinephrine,(stress),Amino acids,1.,Growth hormone,2.Glucocorticiods,3.Catecholamine,Other hormones that act to raise blood glucose,Regulation of hormones on blood glucose,Importance of Glucose Regulation,Too little,Brain problems,Too much,Osmotic water loss(cellular and systemic),Damages blood vessels,Part 4 Disorders of bloodglucose regulation:,Diabetes mellitus,case,Robert,male,18y.,tired,large volume of urine,thirst,losing weight,his breath smelled ketotic.,PE:W 60kg,H 1.75m,pulse 90b.p.m,BP 115/75mmHg,Lab:Urine:glucose+,ketones+,DM(diabetes mellitus,),Characteristics:,Chronic hyperglycemia,Metabolism disturbance,Main symptoms:,Polydipsia,Continuous hunger,Polyuria,Weight loss,Cause:,inadequate production,and/or action of insulin,全球糖尿病流行趋势,2000-2025,Classification of Diabetes Mellitus,（,ADA 1997,）,Type 1 diabetes,A.Immune mediated,B.Idiopathic,Type 2 diabetes,Other specific types,Gestational diabetes mellitus,Oral glucose tolerance test,Aim:to confirm DM.,Method:to measure how the body deals with glucose load.,IFH,CH,I-IFG,IFG+IGT,IPH,I-IGT,FPG(mmol/l),2hr PPG(mmol/l),7.0,6.1,7.8 11.1,5.6,IFG,（,impaired fasting glucose,）,IGT,（,impaired glucose tolerance,）,Type1 diabetes:insulin deficiency,Cause of type1 diabetes,cell destruction,(1)Genetic predisposition:HLA gene,(2)Environmental challenge:inflammation of B cell and attacked by immune system,Results of type1 diatebes,Hyperglycemia,The body response as hypoglycemia,Glycosuria,Ketone bodies,Kussmauls respiration,May lead to ketoacidosis,Growth Failure in children,胰 岛 素,蛋白质分解,脂肪分解,酮体生成,酮血症,酮 尿,酸中毒,昏 迷,脱水,体重,口渴,多饮,高渗性利尿,多尿,(,尿糖,),多食,血 糖,饥饿感,能量不足,糖氧化,葡 萄 糖 利 用,肾糖阈,Complications of type1 diatebes,Diabetic ketoacidosis,Complications of type1 diatebes,Hypoglycemic coma,Cause,Prevention,Treatment,Urine,glucose,ketone body,trace protein,Laboratory Examinations,blood,Glucose,ketone body,HbA1c,FIM,Insulin,、,C,peptide,、,insulin autoantibody,Oral glucose tolerance test,，,IVGTT,C peptide release test,Comprehensive Diabetes Management Plan,Diet,Exercise,Pharmacologic therapy,Monitoring of Blood Glucese,Patient Education,Management of type1 diatebes,Appropriate diet,(1)several small regular meal than one large meal,(2)low in fat and simple carbohydrates,carbohydrates,50-60%,，,fat,20-25%,，,protein15-20%,(3)high vegetables and fruits,(4)avoid alcohol,Appropriate Exercise,Walk is safe.,1.DM:,(1)IDDM:,the only effective drug,(2)NIDDM,(3)DM associated with acute or serious complications:,Ketoacidosis,hyperosmolar nonketotic coma,(4)DM patients under stress conditions,Management of type1 diatebes,Insulin therapy:,2.Other uses,(1),Hyperkalemia and intracellular hypokalemia,GIK(,极化液,):,iv.drip,10,GS 1000ml,Insulin 20u,KCl 3g,(2)Some psychotic disorders,(3)Adjunctive therapy for some diseases,Management of type1 diatebes,Insulin therapy:,Pharmacokinetics of insulin,1.Absorption:,subcutaneous injection(S.C.).,Inhalation,2.Metabolism:,Half life:3-5 min,3.Preparations,Insulin type,Onset,Peak,Duration,Long-acting,Detemir(Levemir),3 to 4 hours,6 to 8 hours,6 to 23 hours,Glargine(Lantus),90 minutes,None,24 hours,Intermediate-acting,NPH(Humulin N),1 to 2 hours,4 to 10 hours,14 or more hours,Short-acting,Aspart(Novolog),15 minutes,1 to 3 hours,3 to 5 hours,Glulisine(Apidra),15 to 30 minutes,30 to 60 minutes,4 hours,Lispro(Humalog),15 minutes,30 to 90 minutes,3 to 5 hours,Regular,30 to 60 minutes,2 to 4 hours,5 to 8 hours,Mixed*,NPH/lispro or aspart,15 to 30 minutes,Dual,14 to 24 hours,NPH/regular,30 to 60 minutes,Dual,14 to 24 hours,*,NPH/regular:Humulin 70/30,Novolin 70/30,Humulin 50/50;NPH/lispro or aspart:Humalog 75/25,Novolog 70/30,Humalog 50/50,.,Onset of action,peak,and duration of exogenous insulin preparations.,Adapted from Hirsch IB.Insulin analogues,.N Engl J Med.,2005;352(2):177,.,1,型糖尿病胰岛素治疗方案,(1),基础,餐前加強疗法,每日注射,4,次,胰岛素,R,胰岛素,N,R 20-45%,早餐前,30,分钟,R 20-30%,午餐前,30,分钟,R 20-30%,晚餐前,30,分钟,N 20-30%,睡前注射,每天总剂量减去,胰岛素,N,量作为,100%,来分配早餐前,午餐前和晚餐前胰岛素用量的百分数,预混型人胰岛素每日注射两次,1,型糖尿病胰岛素治疗方案,(2),Adverse reactions of insulin,1.Hypoglycemia:,most common,Prevention and treatment,2.Insulin allergy,3.Insulin Resistance,Acute resistance,:stress(,anti-insulin substance free fatty acidspH,),Chronic resistance:,1)anti-insulin autoantibody,2)down regulation of receptor,3)dysfunction of glucose transfer,4.Others,Type2 diatebes:relative insulin deficiency,Cause and risk factors of type2 DM,Age greater than 40 years,ethnic groups,including African Americans,Hispanic Americans,Asian Americans,and Native Americans,have a higher risk for diabetes.,Family history of diabetes,Diabetes during a previous pregnancy,Excess body weight(especially around the waist),Given birth to a baby weighing more than 9 pounds,Low activity level(exercising less than 3 times a week),City dwelling,Metabolic syndrome,61,Complications of type2 diatebes,1.Hyperosmolar non-ketotic coma,Dehydrateion,More likely to clot:stroke,AMI,2.Hypoglycaemia,Long-term consequences of poor glycemic control,1992,年糖尿病日,一个与所有国家所有人有关的健康问题,1993,年糖尿病日,糖尿病儿童与成长,1994,年糖尿病日,糖尿病与老年,1995,年糖尿病日,糖尿病和教育，降低无知的代价,1996,年糖尿病日,胰岛素与生命,1997,年糖尿病日,全球的觉醒：改善生命的关键,1998,年糖尿病日,糖尿病人的权利,1999,年糖尿病日,糖尿病的代价,2000,年糖尿病日,新千年糖尿病和生活方式,2001,年糖尿病日,糖尿病,心血管疾病,与社会负担,2002,年糖尿病日,糖尿病与您的,眼睛：,不可忽视的危险因素,2003,年糖尿病日,糖尿病损害,肾脏,2004,年糖尿病日,糖尿病与,肥胖,2005,年糖尿病日,糖尿病与,足部护理,2006,年糖尿病日,糖尿病与脆弱人群,2007,年糖尿病日,关心儿童和青少年糖尿病,2008,年糖尿病日,青少年儿童的糖尿病,2009,年糖尿病日,糖尿病预防与教育,2010,年糖尿病日,糖尿病教育与预防,2011,年糖尿病日,应对糖尿病，立即行动,2012,年糖尿病日,糖尿病，保护我们的未来,65,Nodular glomerulosclerosis,66,Aneurysm Hemorrhage and Exudates,67,68,Bullosis diabeticorum,69,Results of type 2 DM,Need higher levels of insulin secretion,May require insulin in the end.,Management of type 2 DM,Dietary control,Body weight control,Increase physical activity,at least walk for 30 min.per days,Medications,(hypoglycemic agents;insulin),72,新的治疗药物层出不穷,双胍类,动物胰岛素,纯化胰岛素,人胰岛素和半合成胰岛素,磺脲类,甲磺丁脲,氯磺丙脲,醋磺己脲,格列本脲,格列吡嗪,格列美脲,Lispro,Glargine,Aspart,-,糖苷酶抑制剂,阿卡波唐,米格列醇,噻唑烷二酮类,罗格列酮,匹格列酮,胰高血糖素样肽,1,（,GLP1,）,氯茴苯酸类（苯甲酸衍生物）,瑞格列奈,那格列奈,二甲双胍,1920s,1950s,1960s,1970s,1980s,1990s,2000s,73,Oral Antidiabetic agents,Hypoglycemic agents,Sulfonylureas,Non,-,Sulfonylureas,Antihyperglycemic agents,Biguanides,Insulin sensitizers,Inhibitor of,-glycosidase,74,各类抗糖尿病药物的作用部位,磺脲类,瑞格列奈,那格列奈,胰腺,胰岛素分泌受损,葡萄糖,葡萄糖苷 酶抑制剂,肠道,高血糖,HGP,肝脏,葡萄糖摄取,肌肉,二甲双胍,胰岛素增敏剂,胰岛素增敏剂,二甲双胍,Sulfonylureas,（磺酰脲类）,The first generation:,tolbutamide(,甲苯磺丁脲,),chlorpropamide(,氯磺丙脲,),The second generation:,glyburide(,格列本脲,优降糖,),glipizide(,格列吡嗪,美吡哒,),gliquidone(,格列喹酮,糖肾平,),glimepiride(,格列美脲,),The third generation:,gliclazide(,格列齐特，达美康,),Orally hypoglycemic agents,Pharmacological effects of sulfonylureas,1.Hypoglycemic action:,weaker than Insulin,Increasing insulin release,from,cell,:,K,ATP,blockadge,Ca,2+,(2)Enhancing sensitivity of target cell to insulin,Increasing the number and affinity of insulin receptors,(3)Decreasing,glucagons,release from,cell,2.Other effects,(,1)Antidiuretic action,:,chlorpropamide,glyburide,pathway:,reinforcing the role of,ADH,(2),blood platelets aggregation and adhesion,gliclazide,Pharmacological effects of sulfonylureas,Adverse reactions of sulfonylureas,1.Hypoglycemia reactions,2.Gastrointestinal tract reactions,3.Anaphylactic reaction,4.Hepatic damage,Orally Hypoglycemic agents,Non,-,Sulfonylureas,Repaglinide,（瑞格列奈）,Nateglinide,（那格列奈）,可模拟正常人生理性胰岛素分泌,口服给药后迅速起效,半衰期仅,1,小时左右,4,小时后基本代谢清除，两餐之间不刺激胰岛素释放。,发生低血糖的机会较低,Biguanides(,双胍类,),Orally Antihyperglycemic agents,Metformin(,甲福明，二甲双胍,),Phenformin,（苯乙福明，苯乙双胍）,Pharmacological effects of biguanides,1.Antihyperglycemic action,(1)Postponing glucose absorption,(2)Promoting glucose usilization:,anaerobic glycolysis,(3)Inhibiting release of glucagon,2.Other effects,(1)Regulating blood lipid,(2)Antiplatelet effects,Adverse reactions of biguanides,1.Gastrointestinal,irritation,2.,Lactic acidosis,：,phenformin,Insulin sensitizer,Orally Antihyperglycemic agents,Thiazolidinediones(TZD,噻唑烷二酮类）,Rosiglitazone,(,罗格列酮,),Englitazone,(,恩,格列酮,),Pioglitazone,(,吡格列酮,),Troglitazone,(,曲格列酮,),Ciglitazone,(,环,格列酮,),Pharmacological effects of insulin sensitizer,1.Improving insulin resistance,2.Regulating blood lipid,3.Improving vessel complication of NIDDM,4.Improving-cell function,Adverse reactions,of insulin sensitizer,Low incidence of hypoglycemia,Heptic toxicity:,Troglitazone,(,曲格列酮,),水肿、水储留，部分患者的体重增加。,可引起贫血和红细胞减少,-glycosidase inhibitors,Orally Antihyperglycemic agents,Acarbose,（阿卡波糖）,Mechanism of action:,Inhibiting-Glycosidase,(1)decreasing the formation of glucose,(2)slowing the absorption of glucose,Effects of-glycosidase inhibitors,Acute infections or other serious illnesses,Pregnancy,Major surgery,Congestive heart failure,Kidney disease,Liver disease,Use of other drugs(prednisone and some psychiatric medications),Overeating or excessive weight gain,Antibodies that destroy beta cells(in people withtype 1,misdiagnosed as type 2),Progressive loss of beta cell function over many years,When Medications Fail,91,Absolute,Relative,All patients withtype 1 diabetes,Ketoacidosis or severe hyperglycemia(blood sugars over 500),Presence of serious infection(for example,pneumonia),Concurrent illness(such as heart attack),During and after major surgery,During pregnancy,Failure to achieve ideal glycemic control with two or three oral agents,A1c over 10%,A1c over 7.5%plus fasting glucose over 250,Patients who are underweight or losing weight without dieting,Patients who have symptoms from blood sugars over 200,Any patient who is hospitalized,Patients requiring steroids(such as prednisone)for other disorders,Onset of diabetes prior to age thirty,or a duration over fifteen years,Complications such as painful diabeticneuropathy,Indications for Starting Insulin,Starting Insulin,Gestational diabetes,Women without previously diagnosed diabetes are found to have inappropriately high blood sugar levels during pregnancy.,The metabolic syndrome,Diagnosis,Treatment,94,Metabolic Syndrome,THANK YOU,