腸泌素在第二型糖尿病治療的角色 - tsim.org.tw

1 2011 22 401-408.. (incretin) (glucagon-like peptide 1 . GLP-1) (distal ileum) (colon) . GLP-1 ( cells) . (insulin) ( cells) (glucagon) . GLP-1 . GLP-1 (gastric emptying) . (satiety sensation) . GLP-1 -4 (dipeptidyl peptidase 4 DPP-4) .. (incretin action) DPP-4 (incretin mimetics) DPP-4 (DPP-4 inhibitor) .. (Incretin). (Glucagon-like peptide 1 GLP-1). -4 (Dipeptidyl peptidase 4 DPP-4).. 3 . 1960 . 1902 Bayliss Starling . (duodenum) . (jejunum) . 1.. 2. (incretin) . (incretin effect)4 . 100 1 . 402 . - (entero-insular axis) L (open- 1970 (gastric inhibitory peptide type endocrine cells) . glucose-dependent insulinotropic polypeptide (apical surface) . GIP) . (basolateral surface) . GIP .. 1983 proglucagon (acetylcholine) .. (glucagon-like peptide 1 (gastrin-releasing peptide) (leptin) . 5. GLP-1) GLP-1 (insulin) . GIP GLP-1 (somatostatin) 12 . 6 GLP-1(7-37) GLP-1.

2 GLP-1 (7-36) amide GLP-1(9-37) . GIP GLP-1 (9-36) amide . 7. GLP-1 13 . 8 GIP GLP-1 exenatide . 9. ( . GLP-1 (creatinine clearance Ccr 30-89 ml/. min) . (Ccr < 30 ml/min) . GLP-1 . 10. L L exenatide14 . proglucagon DPP-4 sitagliptin . prohormone convertases glicentin 30 100 . GLP-1 (7-37) 29 GLP-1 (Ccr 30-49 ml/min) . (7-36) amide GLP-2 GLP-1 (Ccr < 30 ml/min) . GLP-1 (7-36) amide GLP-1 (7-37) 1/4 15 . GLP-1 (7-36) amide . ( cells)16 . -4 (dipeptidyl peptidase 4 DPP-4) (hypothalamus) . ( ) N 17 . (amino terminus) (dipeptides) . (histidine) (alanine) .. GLP-1 (9-37) GLP-1 (9-36)amide . (glucose transporter) . GLP-1 80% (glucokinase) . GLP-1 GLP-1 20% . 11. (glucose- 403. dependent insulin secretion)18 .. cells GLP-1 . (proliferation) cells (apoptosis) . 19. ( cells) GLP-1 GLP-1 . (somatostatin) . cells (glucagon) . (gluconeogenesis) GLP-1 . 20.)

3 (hepatic glucose output) ( ) GLP-1 . GLP-1 .. (increase satiety sensation) 24 . (decrease appetite)21 GLP-1 . (delay gastric emptying) (GLP-1 receptor agonist) GLP-1 . 22. 60-90 (GLP-1 analogue) DPP-4 . 30 . DPP-4 . DPP-4 GLP-1. GLP-1 25 . GLP-1 . 23. GLP-1 exenatide liraglutide exenatide . 39 Gila Monster GLP-1. ( ) 53% . cells cells Glucagon secretion Pancreas Insulin secretion &. cell survival Muscle, fat, and Liver liver Hepatic glucose Intestine L cells output Glucose disposal GLP--1. GLP. Plasma Plasma glucose glucose Hypothalamus Stomach SSatiety ti t sensation ti &. decreased appetite Weight Gastric emptying (glucagon-like peptide 1 GLP-1) (plasma glucose) . (weight) . 404 . (glycine) (alanine) (substrates) . DPP-4 (nasopharyngitis) . DPP-4 . 26. exenatide DPP-4 . / (polylactide/glycolide) GLP-1 . (bio-degradable) (microsphere) . (weight neutral).

4 GLP-1 DPP-4.. 27. (nausea) (sulfonylurea) . Liraglutide GLP-1 (durability) . 34 (arginine) 26 GLP-1 . (lysine) (glutamate) 16 DPP-4 . (nausea) . DPP-4 Liraglutide 32 . 12 . 28 .. exenatide 1% . 29. metformin ( . liraglutide ) . exenatide 33 . 30 metformin . DPP-4 . sitagliptin saxagliptin . vildagliptin 34 metformin . DPP-4 80% metformin sitagliptin saxagliptin . vildagliptin 24 metformin (lactic 15. DPP-4 acidosis) 35 Sulfonylurea meglitinide GLP-1 DPP-4 (insulin secretagogue) . DPP-8 sitagliptin . Glitazone . 31.. GIP GLP-1 36 . DPP-4 (growth DPP-4 . hormone releasing hormone) . -1 (IGF-1) P (substance P) metformin . (bradykinin) (stromal-derived sulfonylurea/meglitinide glitazone . factor 1 alpha) DPP- 4 . 405. 37 exenatide . metformin sitagliptin vildagliptin . metformin glyburide . 43 . 1% 33 GLP-1 . sitagliptin DPP-4 . DPP-4 metformin . (add-on therapy) glitazone GLP-1.

5 Sulfonylurea exenatide liraglutide (rat) . (benign and malignant 38, 39. Sulfonylurea thyroid C-cell tumors) (male mice). DPP-4 (malignant brosarcomas) . glitazone . 34. GLP-1 . exenatide liraglutide (GLP-1 receptors) GLP-1 . 40. sitagliptine rosiglitazone (calcitonin)44 . insulin glargine 41 . GLP-1 Liraglutide . insulin glargine NPH . 39. NPH liraglutide sulfonylurea . exenatide liraglutide liraglutide . 45 . exenatide liraglutide . GLP-1 . GLP-1 . DPP-4 . GLP-1 .. GLP-1 DPP-4 .. 42. 46 .. Sitagliptin .. 2011 GLP-1 glipizide ALT . exenatide . liraglutide . liraglutide .. 406 . 47 GLP-1 for glucose homeostasis. Discovery of incretin]. Pharm Unserer Zeit 2010; 39: 100-6. 3. Creutzfeldt W. The incretin concept today. Diabetologia 1979; 16: 75-85. 4. Elrick H, Stimmler L, Hlad CJ, Jr., Arai Y. Plasma Insulin GLP-1 2005 . Response to Oral and Intravenous Glucose Administration.

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7 Defective . ampli cation of the late phase insulin response to glucose by DPP-4 GLP-1 GIP in obese Type II diabetic patients. Diabetologia 2002;. 45: 1111-9. 10. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007; 132: 2131-57. 11. Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an . N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab 1995; 80: 952-7. 12. Deacon CF. What do we know about the secretion and degradation of incretin hormones? Regul Pept 2005; 128: GLP-1 117-24. 13. Meier JJ, Nauck MA, Kranz D, et al. Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric . inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. Diabetes 2004;. 53: 654-62.

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