浙江大学医学院：《药理学》课程教学资源（PPT讲稿）胰岛素与口服降糖药 Insulin and oral hypoglycemic drugs

Part 3 Insulin and oral hypoglycemic drugs

llbladder common bile duct pancreatIc duct pancreas duct digestive enzyme ting cells slet of langer hormon ting capillary Endogenous insulin is secreted from B cells in the pancreas

liver stores glucos Diabetes mellitus pancreas secretes as glycogen Insulin↓ or its responses muscle cells store after glycogen and build → blood glucose↑ → Acute or chronic symptoms adipose tis Blood glucose is normal at 75-110 mg/100 ml between liver breaks down glycogen to glucose Glucose metabolism and the regulation by insulin and glucogan pose tssue pancreas secretes breaks down

Vagus Insulin Liver Pancreas Substrate Betacytotropic hormones Fat Muscle Intestine Insulin promotes glucose utilization

Afferent arteriole Efferent arteriole Reabsorption Proximal H2o ADH ADH ADH Collecting duct ess reabsorption of H2o Reabsorption of H2o due to gl Ucose of H2 Normal Diabetes Diabetes state mellitus insipidus Urine 正常人 糖尿病 尿崩症

Different forms of diabetes mellitus Different Forms of Diabetes mellitus General-genetic and other factors not precisel sely Diabetes secondary to pancreatic disease defined Chronic pancreatitis Type 1 diabetes mellitus(formerly called insulin Su urger dependent diabetes mellitus, or IDDM) Tropical diabetes(chronic pancreatitis associated Autoimmune type 1 diabetes mellitus(type 1A) with nutritional and/or toxic factors) Non-autoimmune or idiopathic type I diabetes Diabetes secondary to other endocrinopathies mellitus(type 1B) Cushing' s disease ype 2 diabetes mellitus(formerly called non-insulin- Glucocorticoid administration dependent diabetes mellitus or NIDDM) Acromegaly Specific-defined gene mutations Diabetes secondary to immune suppression Maturity-onset diabetes of youth MODY) Diabetes associated with genetic syndromes; e.g MODY 1 hepatic nuclear factor 4a gene mutations Prader-Willi syndrome ModY 2 glucokinase gene mutations MODY 3 hepatic nuclear factor la gene mutations Diabetes associated with drug therapy (see Table 61-5) MODY 4 pancreatic determining factor x gene mutations MODY X unidentified gene mutation(s) Maternally inherited diabetes and deafness Midd) Mitochondrial leucine tRNa gene mutations Insulin gene mutations Insulin receptor gene mutations

Complications of diabetes mellitus Acute complications a Diabetic ketoacidosis Hyperosmotic nonketotic coma a Chronic complications C ardiovascuar dseases Renal damage Retinal damage Nerve degeneration Infection Myopathy

Antidiabetic drug classification 表32-1降血糖药物的分类 药物分类 代表药 短效人胰岛素、结晶锌胰岛素、中性精蛋白锌胰岛素、鱼精 胰岛素 胰岛素相关药物 蛋白锌胰岛素 胰岛素类似物 门冬胰岛素、赖脯胰岛素、甘精胰岛素 磺酰脲类:甲苯磺丁脲、氯磺丙脲、格列本脲、格列吡嗪、格 作用于KAp通道药 列美脲、格列齐特等 促胰岛素分泌药 氯茴苯酸类/苯丙氨酸行生物瑞格列奈那格列奈 胰高血糖素样肽1激动剂依克那肤igt 二肽基肽酶Ⅳ抑制剂 磷酸西他列汀, Alogliptin*, Linagliptin* 双胍类 二甲双胍,苯乙双胍5 胰岛素增敏剂噻唑烷二酮类化合物 罗格列酮、吡格列酮、环格列酮、曲格列酮3 脂肪酸代谢干扰剂 依托莫司 α-葡萄糖苷酶抑制剂 阿卡波糖,米格列醇,伏格列波糖 胰淀粉样多肽类似物 醋酸普兰林肽 其他 「葡萄糖钠吸收转运蛋白2抑制剂|dgnt 醛糖还原酶抑制剂 依帕司他 注:*表示药物正处于临床实验阶段;5表示药物已撤市

10 s·S- 出9964651234567891011213141516110ooH 234567891011213141516171819( B chain )57 A. Insulin and related agents Connecting peptide 27 4948474645444342414039383736353433323130 PPXGGOLXEXYXOGYXOLXDXEXA③① 30 30

P0、的R即的的55545352515049B418A凶 处唤吧唤吧购吧 43 42 41 PC2 78910111213716少如98 C OH 39 S-S A chal 37 PHE GLU ER LEU TYR GLM UGSN SP 36 VAL c THR SER 56 35 s-S 5 LEU 6901121311516171819202122329、录以 6 S SER chain THR ALA TYR PC3 LEU VAL Structure of insulin