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

Chapter 42 Insulin and oral hypoglycemic drugs 200:Natlonal Geographic Socdety.All rights reserved. nationalgeographic.com

Afferent arteriole Efferent arteriole glucose 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 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 precisely 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 a Acute complications Diabetic ketoacidosis Hyperosmotic nonketotic coma a Chronic complications Cardiovascular diseases a Renal damage Retinal damage Nerve degeneration Infection Myopathy etc

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

Pc八、所的印5551535251504984184 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

A. Insulin and its enhancers Insulin 1. Pharmacological effects ()Carbohydrate metabolism: reducing blood glucose levels by gycogenolysis t, glycogen synthesis t, gluconeogenesis l(ketone ladies l) (2)lipid metabolism: fat synthesis T, lipolysis t, plasma free fatty acidsψ (3) Protein metabolism: active transport of amino acids incorporation of amino acids into protein t, protein catabolism (4)Mechanism of insulin actions Interacting with insulin receptor

INSULIN fatty acids glucose amino acids triglycerides glycogen protei n adipose tissue liver muscle fatty acids stimulated by insulin inhibited by insulin I increased by feeding increased by fasting and in diabetes

330. B1 SS S receptor binding face A21 Structure of insulin

Insulin insulin Sites of glycosylation S-S S-S S-S IS-S Cell membrane ①P P①①P ATP、( inase ADP ATP、( Kinase)yADP phosphorylated protein