書籍詳細

1. インクレチン―概念と研究の歩み

P.16 掲載の参考文献

• 1) Bayliss WM, Starling EH:The mechanism of pancreatic secretion. J Physiol 28:325-353, 1902
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• 2) Moore B:On the treatment of Diabetus mellitus by acid extract of Duodenal Mucous Membrane. Biochem J1 (1):28-38, 1906

• 3) Zunz E, La Barre J:Contributions a letude des variations physiologiques de la secretion interne du pancreas. relations entre les secretions externe et interne du pancreas. Arch Int Physiol Biochim 31:20-44, 1929

• 4) La Barre J:Sur les possibilitites d'un traitement du diabete par l'incretine. Bull Acad R Med Belg 12:620-634, 1932

• 5) Yalow RS, Berson SA:Immunoassay of endogenous plasma insulin in man. J Clin Invest 39:1157-1175, 1960

• 6) Elrick H et al:Plasma Insulin Response to Oral and Intravenous Glucose Administration. J Clin Endocrinol Metab 24:1076-1082, 1964
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• 7) McIntyre N et al:New interpretation of oral glucose tolerance. Lancet 2 (7349):20-21, 1964
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• 8) Brown JC et al:Further purification of a polypeptide demonstrating enterogastrone activity. J physiol 209:57-64, 1970
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• 9) Dupre J et al:Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab 37:826-828, 1973

• 10) Taminato T et al:Synthetic Gastric Inhibitory Polypeptide Stimulatory Effect on Insulin and Glucagon Secretion in the Rat. Diabetes 26 (5):480-484, 1976

• 11) Ebert R et al:Preservation of Incretin Activity After Removal of Gastric Inhibitory Polypeptide(GIP)from Rat Gut Extracts by lmmunoadsorption. Diabetologia 24 (6):449-459, 1983
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• 12) Inagaki N et al:Gastric inhibitory polypeptide:structure and chromosomal localization of the human gene. Mol Endocrinol 3 (6):1014-1021, 1989
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• 13) Takeda J et al:Sequence of an intestinal cDNA encoding human gastric inhibitory polypeptide precursor. Proc Natl Acad Sci USA 84 (20):7005-7008, 1987
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• 14) Holst JJ:The physiology of glucagon-like peptide 1. Physiol Rev 87 (4):1409-1439, 2007
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• 15) Holst JJ et al:Gut glucagon and reactive hypoglycemia. Lancet 1:1008, 1973
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• 16) Bell GI et al:Hamster preproglucagon contains the sequence of glucagon and two related peptides. Nature 302:716-718, 1983
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• 17) Schmidt WE et al:Glucagon-like peptide-1 but not glucagon-like-2 stimulates insulin release from isolated rat pancreatic islets. Diabetlogia 28:704-707, 1985

• 18) Kreymann B et al:Glucagon-like peptide-17-36:a physiological incretin in man. Lancet 2 (8571):1300-1304, 1987

• 19) Yamada Y et al:Human gastric inhibitory polypeptide receptor:cloning of the gene(GIPR)and cDNA. Genomics 29 (3):773-776, 1995
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• 20) Usdin TB et al:Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain. Endocrinology 133:2861-2870, 1993
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• 21) Stoffel M et al:Human glucagon-like peptide-1 receptor gene:localization to chromosome band 6p21 by fluorescence in situ hybridization and linkage of a highly polymorphic simple tandem repeat DNA polymorphism to other markers on chromosome 6. Diabetes 42:1215-1218, 1993
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• 22) Thorens B:Expression cloning of the pancreatic beta cell receptor for the gluco-incretin hormone glucagon-like peptide 1. Proc Natl Acad Sci USA 89 (18):8641-8645, 1992
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• 23) Scrocchi LA et al:Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med 2 (11):1254-1258, 1996
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• 24) Miyawaki K et al:Glucose intolerance caused by a defect in the entero-insular axis:A study in gastric inhibitor polypeptide receptor knockout mice. Proc Natl Acad Sci USA 96 (26):14843-14847, 1999

• 25) Deacon CF et al:Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 44:1126-1131, 1995
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• 26) Meier JJ 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 53:654-662, 2004
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• 27) Orskov C et al:Secretion of the incretin hormones glucagon-like peptide-1 and gastric inhibitory polypeptide correlates with insulin secretion in normal man throughout the day. Scand J Gastroenterol 31:665-670, 1996
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• 28) Vollmer K et al:Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Ddiabetes 57:678-687, 2008

• 29) Takemura J et al:Hypersecretion of gastric inhibitory polypeptide induced by glucose ingestion in diabetes mellitus. Endocrinol Jpn 28 (1):17-21, 1981
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• 30) Takemura J et al:The role of endogenous gastric inhibitory polypeptide in the enteroinsular axis. J Clin Endocrinol Metab 54:909-913, 1982

• 31) Andreasen JJ et al:Secretion of glucagon-like peptide-1 and reactive hypoglycemia after partial gastrectomy. Digestion 55 (4):221-228, 1994
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• 32) Qualmann C et al:Glucagon-like peptide 1(7-36 amide) secretion in response to luminal sucrose from the upper and lower gut. A study using alpha-glucosidase inhibition (acarbose). Scan J Gastroenterol 30:892, 1995

• 33) Narita T et al:Miglitol induces prolonged and enhanced glucagon-like peptide-1 and reduced gastric inhibitory polypeptide responses after ingestion of a mixed meal in Japanese Type 2 diabetic patients. Diabet Med 26 (2):187-188, 2009
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• 34) Ross SA et al:Hypersecretion of Gastric Inhibitory Polypeptide Following Oral Glucose in Diabetes Mellitus. Diabetes 26 (6):525-529, 1977
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• 35) Toft-Nielsen MB et al:Determinant of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 86:3717-3713, 2001

• 36) Vilsboll T et al:Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 50:609-613, 2001
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• 37) Nauck MA et al:Preserved incretin activity of glucagon-like peptide 1[7-36 amide]but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 91:301-307, 1993

• 38) Vilsboll T et al:Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. Diabetologia 45:1111-1119, 2002
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• 39) Yamada Y et al:Pancreatic and extrapancreatic effects of gastric inhibitory polypeptide. Diabetes 55:S86-S91, 2006

• 40) Zander M et al:Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and b-cell function in type 2 diabetes:a parallel-group study. Lancet 359:824-830, 2002

• 41) Amori RE et al:Efficacy and safety of incretin therapy in type 2 diabetes:systematic review and meta-analysis. JAMA 298:194-206, 2007
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• 42) Nonaka K et al:Efficacy and safety of sitagliptin monotherapy in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract 79 (2):291-298, 2008
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• 43) Kikuchi M et al:Vildagliptin dose-dependently improves glycemic control in Japanese patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 83 (2):233-240, 2009
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• 44) Seino Y et al:Dose-dependent improvement in glycemia with once-daily liraglutide without hypoglycemia or weight gain:A double-blind, randomized, controlled trial in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract 81 (2):161-168, 2008
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• 45) Hirasawa A et al:Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 11:90-94, 2005
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• 46) Shibasaki T et al:Essential role of Epac2/Rapl signaling in regulation of insulin granule dynamics by cAMP. Proc Natl Acad Sci USA 104 (49):19333-19338, 2007

2. GIP, GLP-1の多彩な作用

P.24 掲載の参考文献

• 1) Brown JC et al:A gastric inhibitory polypeptide. II. The complete amino acid sequence. Can J Biochem 49:867-872, 1971
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• 2) Dupre J et al:Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab 37:826-828, 1973

• 3) Schauder P et al:Gastric inhibitory polypeptide:effect on glucose-induced insulin release from isolated rat pancreatic islets in Vitro. Diabetologia 11:483-484, 1975
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• 4) Takeda J et al:Sequence of an intestinal cDNA encoding human gastric inhibitory polypeptide precursor. Proc Natl Acad Sci USA 84:7005-7008, 1987
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• 5) Ugleholdt R et al:Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor. J Biol Chem 281:11050-11057, 2006
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• 6) Yamada Y et al:Human gastric inhibitory polypeptide receptor:cloning of the gene(GIPR)and cDNA. Genomics 29:773-776, 1995
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• 7) Narita T et al:Miglitol induces prolonged and enhanced glucagon-like peptide-1 and reduced gastric inhibitory polypeptide responses after ingestion of a mixed meal in Japanese Type 2 diabetic patients. Diabet Med 26:187-188, 2009
  pubmed

• 8) Miyawaki K et al:Glucose intolerance caused by a defect in the entero-insular axis:a study in gastric inhibitory polypeptide receptor knockout mice. Proc Natl Acad Sci USA 96:14843-14847, 1999

• 9) Kim SJ et al:Glucose-dependent insulinotropic polypeptide (GIP) stimulation of pancreatic beta-cell survival is dependent upon phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling, inactivation of the forkhead transcription factor Foxo1, and down-regulation of bax expression. J Biol Chem 280:22297-22307, 2005
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• 10) Pamir N et al:Glucose-dependent insulinotropic polypeptide receptor null mice exhibit compensatory changes in the enteroinsular axis. Am J Physiol Endocrinol Metab 284:E931-939, 2003
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• 11) Scrocchi LA et al:Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med 2:1254-1258, 1996
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• 12) Hansotia T et al:Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. Diabetes 53:1326-1335, 2004
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• 13) Miyawaki K et al:Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med 8:738-742, 2002
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• 14) Yamada Y et al:Pancreatic and extrapancreatic effects of gastric inhibitory polypeptide. Diabetes 55 (S2):S86-S91, 2006

• 15) Yamada C et al:Genetic inactivation of GIP signaling reverses aging-associated insulin resistance through body composition changes. Biochem Biophys Res Commun 364:175-180, 2007
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• 16) Gault VA et al:Chemical gastric inhibitory polypeptide receptor antagonism protects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat and cafeteria diets. Diabetologia 50:1752-1762, 2007
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• 17) Tsukiyama K et al:Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation after food ingestion. Mol Endocrinol 20:1644-1651, 2006
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P.37 掲載の参考文献

• 1) 宮川潤一郎ほか:糖尿病:診断と治療の進歩, IV. 最近の話題, 2. インクレチン関連治療. 日本内科学会雑誌 98 (4):809-816, 2009

• 2) 宮川潤一郎ほか:インクレチンをめぐる新知見, 4. GLP-1受容体作動薬による糖尿病治療. 糖尿病 52 (6):427-431, 2009

• 3) Ahren B:Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes. Nat Rev Drug Discovery 8:369-385, 2009

• 4) Tolhurst G et al:Nutritional regulation of glucagon-like peptide-1 secretion. J Physiol 587 (1):27-32, 2009
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• 5) Baggio LL, Drucker DJ:Biology of incretins:GLP-1 and GIP. Gastroenterology 132:2131-2157, 2007
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• 6) Holst JJ:The physiology of the glucagon-like peptide 1. Physiol Rev 87:1409-1439, 2007
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• 7) Zhang C-L et al:The cAMP sensor Epac2 is a direct target of antidiabetic sulfonylurea drugs. Science 325 (5940):607-610, 2009
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• 8) Butler AE et al:B cell deficit and increased B cell apoptosis in humans with type 2 diabetes. Diabetes 52:102-110, 2003

• 9) Wang Q, Brubaker PL:Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice. Diabetologia 45:1263-1273, 2002.
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• 10) Tourrel C et al:Glucagon-like peptide-1 and exendin-4 stimulate beta-cell neogenesis in streptozotocintreated newborn rats resulting in persistently improved glucose homeostasis at adult age. Diabetes 50:1562-1570, 2001

• 11) Tourrel C et al:Persistent improvement of type 2 diabetes in the Goto-Kakizaki rat model by expansion of the beta-cell mass during the prediabetic period with glucagon-like peptide-1 or exendin-4. Diabetes 51:1443-1452, 2002
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• 12) Zhang J et al:Continuous stimulation of human glucagon-like peptide-1(7-36) amide in a mouse model (NOD) delays onset of autoimmune type 1 diabetes. Diabetologia 50:1900-1909, 2007

• 13) List JF, Hebener JF:Glucagon-like peptide 1 agonists and the development and growth of pancreatic β-cells. Am J Physiol Metab 286:E875-E881, 2004

• 14) Li Y et al:B-cell PDX-1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. Diabetes 54:482-491, 2005

• 15) Klinger S et al:Increasing GLP-1-induced B-cell proliferation by silencing the negative regulators of signaling cAMP response element modulator a and DUSP14. Diabetes 57:584-593, 2008

• 16) Farilla L et al:GLP-1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 144:5149-5158, 2003
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• 17) Hui H et al:Glucagon-like peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5'-adenosine monophosphate-dependent protein kinase-A-and a phosphatidylinositol-3-kinase-dependent pathway. Endocrinology 144:1444-11455, 2003

• 18) Jhala US et al:cAMP promotes pancreatic beta cell survival via CREB-mediated induction of IRS2. Genes Dev 17:1575-1580, 2003
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• 19) Xu G et al:Exendin-4 stimulates both beta cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes 48:2270-2276, 1999
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• 20) Zhou J et al:Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells:involvement of PDX-1 and HNF3beta transcription factors. J Cell Physiol 192:304-314, 2002
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• 21) Zhou J et al:Glucagon-like peptide 1 and exendin-4 convert pancreatic AR42J cells into glucagon and insulin-producing cells. Diabetes 48:2358-2366, 1999
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• 22) Hadjiyanni I, Drucker DJ:Glucagon-like peptide 1 and type 1 diabetes:NOD ready for prime time? Endocrinology 148 (11):5133-5135, 2007
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• 23) Xue S et al:Exendin-4 therapy in NOD mice with new-onset diabetes increases regulatory T cell frequency. Immunology of Diabetes V:Ann NY Acad Sci 1150:152-156, 2008

• 24) Nauck MA et al:Effects on glucagon1-like peptide-1 on counterregulatory hormone response, cognitive functions, and insulin secretion during hyperinsulinemic stepped by polygemic clump experiments in healthy voluntiers. J Clin Endocrinol Metab 87:1239-1246, 2002

• 25) Matsumura T et al:Glucagon-like peptide-1 (7-36) amide supresses glucagon secretion and decreases cyclic AMP concentration in cultured in-RI-G9 cells. Biochem Biophys Res Commun 186:503-508, 1992

• 26) Tornehave D et al:Expression of GLP-1 receptor in mouse, rat, and human pancreas. J Histochem Cytochem 56:841-851, 2008
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• 27) Abu-Hamdah R et al:Clinical review:The extrapancreatic effects of glucagon-like peptide-1 and related peptides. J Clin Endocrinol Metab 94 (6):1843-1852, 2009
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• 28) Drucker DJ, Asa S:Glucagon gene expression in vertebrate brain. J Biol Chem 263:13475-13478, 1988

• 29) Orskov C et al:Glucagon-like peptide 1 receptors in the subfornical organ and the area postrema are accessible to circulating glucagon-like peptide 1. Diabetes 45:832-835, 1996
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• 30) Nauck MA et al:Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 273:981-988, 1997

• 31) Schirra J, Goke B:The physiological role of GLP-1 in humans:incletin, ileal brake or more? Regul Pept 128:109-115, 1997
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• 32) Prigeon RL et al:Suppression of endogenous glucose production by glucagon-like peptide-1 independent of islet hormones:a novel extrapancreatic effect. Am J Physiol 285:E701-707, 2003

• 33) Dardevet D et al:Insulin-independent effect of GLP-1 on canine liver glucose metabolism:duration of infusion and involvement of hepatoportal region. Am J Physiol Endocrinol Metab 287:E75-81, 2004
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• 34) Morales M et al:Preserved GLP-1 effects on glycogen synthase a activity and glucose metabolism in isolated hepatocytes and skeletal muscle from diabetic rats. Diabetes 46:1264-1269, 1997

• 35) Redondo A et al:Cell signaling in the GLP-1 action in the rat liver. Mol Cell Endocrinol 204:43-50, 2003
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• 36) Ding X et al:Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology 43:173-181, 2006
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• 37) Egan JM et al:Glucagon-like peptide-1 auguments insulin-mediated glucose uptake in the obese state. J Clin Endocrinol Metab 87:3768-3773, 2002

• 38) Acitores A et al:Cell signalling of glucagon1-like peptide-1 action in rat skeletal muscle. J Endocrinol 180:389-398, 2004

• 39) Gonzalez N et al:Effect of GLP-1 on glucose transport and its cell signalling in human myocytes. Regul Pept 126:203-211, 2005
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• 40) Alcantara AI et al:Exendin-4 agonist and exendin(9-39) amide antagonist of the GLP-1(7-36) amide effects in liver and muscle. Arch Biochem Biophys 341:1-7, 1997
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• 41) Morales M et al:Preserved GLP-1 effects on glycogen synthase activity and glucose metabolism in isolated hepatocytes and skeletal muscle from diabetic rats. Diabetes 46:1264-1269, 1997

• 42) Wang Y et al:Regulation of glucose transporters and hexose uptake in 3T3-L1 adipocytes:glucagon-like peptide-1 and insulin interaction. J Mol Endocrinol 19:241-248, 1997

• 43) Villanueva-Penacarrillo ML et al:Effect of GLP-1 treatment on GLUT2 and GLUT4 expression in type1 and type 2 rat diabetic models. Endocrine 15:241-248, 2001

• 44) Luque MA et al:Glucagon-like peptide-1 (GLP-1) and glucose metabolism in human myocytes. J Endocrinol 173:465-473, 2002
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• 45) Miki H et al:Glucagon-like peptide-1(7-36)amide enhances insulin-stimulated glucose uptake and decreases intracellular cAMP content in isolated rat adipocytes. Biochim Biophys Acta 1312:132-136, 1996
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• 46) Gao H et al:GLP-1 amplifies insulin signaling by up-regulation of IRbeta, IRS-1 and Glut4 in 3T3-L1 adipocytes. Endocrine 32:90-95, 2007
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• 47) Sancho V et al:Effects of glucagon-like peptide-1 and exendins on kinase activity, glucose transport and lipid metabolism in adipocytes from normal and type 2 diabetic rats. J Mol Endocrinol 35:27-38, 2005
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• 48) Sancho V et al:The action of GLP-1 and exendins upon glucose transport in normal human adipocytes, and on kinase activity as compared with morbidly obese patients. Int J Mol Med 19:961-966, 2007

• 49) Qin X et al:GLP-1 reduces intestinal lymph flow, triglyceride absorption, and spilipoprotein production in rats. Am J Physiol Gastrointest Liver Physiol 288:G943-G949, 2005
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• 50) Watanabe N et al:Trophic effect of glucagon-(1-21)-peptide on the isolated rat ileal mucosal cells. Biochem Biophys Res Commun 152:1038-1044, 1988
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• 51) Mannucci E, Rotella CM:Future perspectives on glucagon-like peptide-1, diabetes and cardiovascular risk. Nut Metab Cardiovasc Dis 18:672-648, 2008

• 52) Sokos GG et al:Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail 12:694-699, 2006
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• 53) Gros R et al:Cardiac function in mice lacking the glucagon-like-peptide-1 receptor. Endocrinology 144:2242-2252, 2003
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• 54) Yamamoto H et al:Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons. J Clin lnvest 110:43-52, 2002

• 55) Bose AK et al:Glucagon-like peptide-1 can directly protect the heart against ischemia/reperfusion injury. Diabetes 54:145-151, 2005

• 56) Ban K et al:Cardioprotective and vasodilatory actions of glucagon-like peptide-1 are mediated through both glucagon-like peptide-1-dependent and independent pathways. Circulation 117:2340-2350, 2008
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• 57) Noyan-Ashraf MH et al:GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infraction in mice. Diabetes 58:975-983, 2009

• 58) Nikolaidis LA et al:Effects of glucagon-like peptide-1 in patients with acute myocardial infraction and left ventricular dysfunction after successful reperfusion. Circulation 109:962-965, 2004

• 59) Nystrom T et al:Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab 287:E1209-E1215, 2004
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• 60) Liu H et al:Glucagon-like peptide-1 attenuates tumor-necrosis factor-alpha-mediated induction of plasminogen activator inhibitor-1 expression. J Endocrinol 196:57-65, 2008
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• 61) 大村 裕, 坂田利家:脳と食欲-頭で食事をする. 大村 裕, 中川八郎編, ブレインサイエンス・シリーズ9, 共立出版, 1996

• 62) Kauf C et al:Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage. J Clin Invest 115 (12):3554-3563, 2005

• 63) D'Alessio DA et al:New ways in which GLP-1 can regulate glucose homeostasis. J Clin Invest 115 (12):3406-3408, 2005

• 64) Cabou C et al:Brain glucagon-like peptide-1 regulates arterial blood flow, heart rate, and insulin sensitivity. Diabetes 57:2577-2587, 2008
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• 65) Zheng D et al:Exenatide sensitizes insulin-mediated whole-body glucose disposal and promotes uptake of exogenous glucose by the liver. Diabetes 58:352-359, 2009
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• 66) 宮川潤一郎, 難波光義:消化管由来ホルモン, GIP, GLP-1とインスリン抵抗性. アディポサイエンス 4 (1):17-24, 2007
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3. GLP-1誘導体

P.45 掲載の参考文献

• 1) Drucker DJ, Nauck MA:The incretin system:glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696-1705, 2006
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• 2) Agerso H et al:The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia 45:195-202, 2002
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• 3) Marre M et al:Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes(LEAD-1 SU). Diabet Med 26:268-278, 2009
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• 4) Nauck M et al (LEAD-2 study group):Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes. Diabetes Care 32:84-90, 2009

• 5) Garber A et al (LEAD 3 Mono study group):Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono):a randomized, 52-week, phase 3, double-blind, parallel-treatment trial. Lancet 373:473-481, 2009

• 6) Seino Y et al:Dose-dependent improvement in glycemia with once-daily liraglutide without hypoglycemia or weight gain:a double-blind, randomized, controlled trial in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract 81:161-168, 2008
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• 7) Matthews JE et al:Pharmacodynamics, pharmacokinetics, safety, and tolerability of albiglutide, a long-acting glucagon like peptide-1 mimetic, in patients with type 2 diabetes. J Clin Endocrinol Metab 93:4810-4817, 2008
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• 8) Berria R et al:8weeks treatment with R15883, a novel long-acting, human GLP-1 analogue improves beta cell function in metformin-treated diabetic subjects:a double-blind, placebo-controlled phase 2 study. Diabetologia 51(Suppl 1):S347, 2008

4. エキセンジン-4

P.52 掲載の参考文献

• 1) Eng J et al:Isolation and characterization of Exendin-4, an Exendin-3 analogue, from Heloderma suspectum Venom. J Biol Chem 267:7402-7405, 1992

• 2) Goke R et al:Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting β-cells. J Biol Chem 268:19650-19655, 1993

• 3) Fehse F et al:Exenatide augments first-and second-phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes. J Clin Endoclinol Metab 90:5991-5997, 2005

• 4) Tourrel C et al:Persistent improvement of type 2 diabetes in the Goto-Kakizaki rat model by expansion of the B-cell mass during the prediabetic period with glucagons-like peptide-1 or exendin-4. Diabetes 51:1443-1452, 2002
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• 5) Fineman MS et al:Effectiveness of progressive dose-escalation of exenatide (exendin-4) in reducing dose limiting side effects in subjects with type 2 diabetes. Diabetes Metab Res Rev 20:411-417, 2004
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• 6) Buse JB et al;Exenatide-113 Clinical Study Group:Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 27:2628-2635, 2004
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• 7) Kendall DM et al:Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 28:1083-1091, 2005

• 8) Defronzo RA et al:Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 28:1092-1100, 2005
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• 9) Klonoff DC et al:Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 24:275-286, 2008
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• 10) Nathan DM et al:Medical management of hyperglycemia in type 2 diabetes:a consensus algorithm for the initiation and adjustment of therapy:a consensus statement of the american diabetes association and the european association for the study of diabetes. Diabetes Care 32:193-203, 2009

• 11) Zinman B et al:The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes:a randomized trial. Ann Intern Med 146:477-485, 2007
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• 13) Yoon NM et al:Exenatide added to insulin therapy:a retrospective review of clinical practice over two years in an academic endocrinology outpatient setting. Clin Ther 31:1511-1523, 2009

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5. DPP-4阻害薬

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6. インクレチン治療の展開

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