10、RTK (L) P Extracellular Cytoplasm 1 insulin binds LR 2 IRTK (L) activated OP OP 3 IRTK (R) phosphorylated/ activated PO PO 4 IRTK (L) phosphorylated OP OP P PPP ATPs ADPs Phosphorylation catalyzed by IRTK (L) ATPs ADPs P P Phosphorylation catalyzed by IRTK (R) Activation of the tyrosine kinase domai 。

11、ns of the insulin receptor by insulin binding, followed by interchain autophosphorylation Insulin Signal Transduction q several targets are phosphorylated by IRTK q IRS activation is tied to metabolic responses v glucose transport (muscle and fat cells) v activation of protein phosphatase q protein。

12、phosphatase removes phosphates from proteins phosphorylated by protein kinase A counter-regulation of glucagon Insulin Action（胰岛素的作用）（胰岛素的作用） Insulin promotes the uptake of glucose into many tissues that express GLUT4 glucose transporters, such as skeletal muscle and fat. Insulin increases the activ 。

13、ity of these transporters and increases their numbers by stimulating their recruitment from an intracellular pool to the cell surface. Extracellular space Cytoplasm tyr-OH IRS 4 signals Golgi to traffic GLUT-4 to membrane PKB GOLGI = GLUT-4 Active IRTKPO PO OP OP 1 IRTK catalyze d tyr-OP IRS ATP ADP 。

14、 active IRS tyr-OP IRS PI- 3K p85 2 activated by docking active IRS Hypothetical mechanism for insulin to mobilize GLUT-4 transporter to the plasma membrane in muscle and adipose tissue. IRS, insulin-receptor substrate;
IRTK, insulin receptor tyrosine kinase;
PI-3K, phosphatidyl-inositol kinase;
PDK 。

15、;
phospholipid-dependent kinase PKB, protein kinase B tyr-OP IRS tyr-OP IRS tyr-OP IRS PIP2 PIP3 PDK + + Insulin stimulated glucose transport (GLUT-4) in adipose or muscle cells Golgi glucose transporter Step1 - insulin binding and signal transduction (signal) -P P- Step 2 translocation From Golgi S 。

16、tep 3 Binding and fusion Step 4 Glucose transport Step 5 Receptor inactivation Step 6 translocation back to Golgi Glucose Diagnostic criteria World Health Organization (1980) 1. Symptoms of diabetes plus a plasma glucose concentration 11.1 mmol/l obtained at any time of day and without regard to mea 。

17、ls, OR 2. Fasting plasma glucose 7.8 mmol/l, OR 3. A plasma glucose concentration 11.1 mmol/l 2 h after 75 g of oral glucose 糖尿病的诊断糖尿病的诊断 Classification Diabetes is classified by underlying cause. The categories are: Type 1 diabetesan autoimmune disease in which the bodys own immune system attacks t 。

18、he pancreas, rendering it unable to produce insulin;
Type 2 diabetesin which a resistance to the effects of insulin or a defect in insulin secretion may be seen;
Gestational diabetes Insulin resistance Genetic susceptibility, obesity, Western lifestyle Type 2 diabetes IR -cell dysfunction Abnormal g 。

19、lucose tolerance Hyperinsulinemia, then -cell failure Normal IGT*Type 2 diabetes Post- prandial glucose Insulin resistance Increased insulin resistance Fasting glucose Hyperglycemia Insulin secretion *IGT = impaired glucose tolerance Insulin resistant;
low insulin secretion (54%) Insulin resistant;
。

【内分泌|内分泌的分子生物学final】20、good insulin secretion (29%) Insulin sensitive;
good insulin secretion (1%) Insulin sensitive;
low insulin secretion (16%) 83% Haffner SM, et al. Circulation 2000;
101:975980. Insulin resistance Glucose output Glucose uptake Glucose uptake Hyperglycemia LiverMuscle Adipose tissue IR In USA: 16 milli 。

21、on people suffer from DM. Type 1 diabetes accounts for 5-10% of cases, affecting 1 of 400 children and adolescents. Type 2 diabetes is extremely common, accounting for 90-95% of all cases of diabetes. This form of diabetes can go undiagnosed for many years, but the number of cases that are being dia 。

22、gnosed is rising rapidly, leading to reports of a diabetes epidemic. Epidemiology 2003年全球糖尿病病人已超过年全球糖尿病病人已超过1.94亿 ， 预计到本世纪亿 ， 预计到本世纪 2025年这个数字将增加近一倍（年这个数字将增加近一倍（3.33亿）亿） 我国糖尿病病人数约我国糖尿病病人数约4000万 ， 占全球糖尿病病人的万 ， 占全球糖尿病病人的1/5. 型糖尿病占型糖尿病占5.6 ， 型糖尿病占 ， 型糖尿病占93.7 ， 其它类型糖尿病 ， 其它类型糖尿病 仅占仅占0.7 。
Genetic associations（遗传关联）（遗传关 。

23、联） The clearest association is with class II human leucocyte antigens (HLA) coded on the short arm of chromosome 6. This locus has been termed IDDM1. The region around the gene coding for insulin is termed IDDM2 and there are associations with loci on chromosomes 15q (IDDM3), 11q (IDDM4) and 6q (IDD 。

24、M5). The number of mutations at other putative sites continues to increase but the exact nature of these associations is not known. Studies in twins indicate that approximately 40% of the risk of type 1 DM is genetic. etiology of type 1 DM Environmental factors（环境因素）（环境因素） Viruses. Evidence for a vi 。

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标题：内分泌|内分泌的分子生物学final( 二 )