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El efecto incretina y su participación en la diabetes mellitus tipo 2
Resumen
Las incretinas son hormonas producidas en el tracto gastrointestinal en respuesta a la ingesta de alimentos y con efecto sobre las células de los islotes de Langerhans, que aumentan la secreción y liberación de la insulina y disminuyen la secreción de glucagón dependiendo de la glucosa circulante. Las principales incretinas son el GLP1 y el GIP. El “efecto incretina” consiste en la mayor liberación de insulina por el páncreas cuando el estímulo de glucosa es gastrointestinal, comparado a cuando el estímulo es endovenoso. Este efecto está alterado en pacientes con diabetes tipo 2. El efecto incretina se puede aumentar de dos formas: producir un GLP1 que no sea inactivado por DPP4, es decir, un análogo de GLP1; o inhibir a la enzima que desactiva a las incretinas mediante lo que se llama inhibidores de DPP4. Hay dos análogos de GLP1, exenatide y liraglutide, y algunos otros en investigación. Hay tres inhibidores de DPP4: sitagliptina, vildagliptina y saxagliptina. Con ellos se logrará mejorar la glucemia en pacientes con DM2 y, por lo tanto, la hemoglobina glucosilada, con un perfil de seguridad adecuado, baja posibilidad de hipoglucemias y sin incremento o disminución de peso en los pacientes.
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Salehi M, Beneridkt A, D’Alessio DA. Targeting β cell mass in type 2 diabetes: promise and limitations of new drugs based on incretins. Endocr Rev. 2008; 29 (3):367-379.
Chia CW, Egan JM. Incretin based therapies in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2008; 93 (10):3703-3716.
Murphy KG, Dhillo WS, Bloom SR. Gut peptides in the regulation of food intake and energy homeos-tasis. Endocr Rev. 2006; 27 (7):719-727.
D’Alessio DA, Denney AM, Hermiller LM, Prigeon RL, Martin JM, Tharp WG, et al. Treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin improves fasting islet-cell function in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2009; 94 (1):81-88.
Vilsboll T, Krarup T, Deacon CF, Madsbad S, Holst JJ. Reduced post-prandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001; 50 (3):609-613.
Abu-Hamdah R, Rabiee A, Meneilly GS, Shannon RP, Andersen DK, Elahi D. The extrapancreatic effects of glucagon-like peptide-1 and related peptides. J Clin Endocrinol Metab. 2009; 94 (6): 1843-1852.
Kjems LL, Holst JJ, Volund A, Madsbad S. The influence of GLP1 on glucose-stimulated insulin secretion: effects on β-cell sensitivity in type 2 and nondiabetic subjects. Diabetes. 2003; 52 (2):380-386.
Gutzwiller JP, Goke B, Drewe J, Hildebrand P, Ketterer S, Handschin D, et al. Glucagon like peptide-1: a potent regulator of food intake in humans. Gut. 1999; 44 (1):81-86.
Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metfor-min and a sulfonylurea. Diabetes Care. 2005; 28 (5):1083-1091.
Ebert R, Creutzfeldt W. Gastrointestinal peptides and insulin secretion. Diabetes Metab Rev. 1987; 3 (1):1-26
Vilsboll T, Brock B, Perrild H, Levin K, Lervang HH, Kolendorf K, et al. Liraglutide, a once-daily human GLP-1 analogue improves β-cell function and arginine-stimulated insulin secretion at hyperglycaemia in patients with Type 2 diabetes mellitus. Diabet Med. 2008; 25:152-156.
Kieffer TJ, Habener JF. The glucagon-like peptides. Endocr Rev. 1999; 20 (6):876-913.
Baggio LL, Drucker DJ. Biology of incretins: GLP1 and GIP. Gastroenterology. 2007; 132 (6):2131-2157.
Knop FK, Vilsboll T, Hojberg PV, Larsen S, Madsbad S, Volund A, et al. Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state? Diabetes. 2007; 56 (8):1951-1959.
Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagons-like peptide 1 (7-36 amide) but not of synthetic human gastric inhibitory polypeptide in patients type 2 diabetes mellitus. J Clin Invest. 1993; 91(1):301-307.
Rachman J, Barrow BA, Levy JC, Turner RC. Near normalization of diurnal glucose concentrations by continuous administration of glucagon–like peptide 1 (GLP1) in subjects with NIDDM. Diabetologia. 1997; 4 (2)0:205-211.
Zander M, Madsbad S, Madsen JL, Holst JJ. Effects of 6-week course of glucagon like peptide 1 on glycaemic control, insulin sensitivity, and β-cell function in type 2 diabetes: a parallel-group study. Lancet. 2002; 359 (9309):824-830.
Bonner-Weir S. Is let growth and development in the adult. J Mol Endocrinol. 2000; 24:297-302.
Finegood DT, Scaglia L, Bonner Weir S. Dynamics of β-cell mass in the growing rat pancreas. Estimation with a simple mathematical model. Diabetes. 1995; 44:249-256.
Wang H, Iezzi M, Theander S, Antinozzi PA, Gauthier BR, Halban BA, et al. Supression of Pdx-1 perturbs proinsulin processing, insulin secretion and GLP1 signaling in INS-1 cells. Diabetologia. 2005; 48 (4):720-731.
Ghofaili KA, Fung M, Ao Z, Meloche M, Shapiro RJ, Warnock GL, et al. Effect of exenatide on β cell transplantation in type 1 diabetes. Transplantation. 2007; 83 (1):24-28.
Amiranoff B, Vauclin-Jacques N, Laburthe M. Functional GIP receptors in a hamster pancreatic β cell line, in 111: specific binding and biological effects. Biochem Biophys Res Commun. 1984; 123 (2):671-676.
Gromada J, Bokvist K, Ding WG, Holst JJ, Nielsen JH, Rorsman P. Glucagon like peptide 1(7-36) amide stimulates exocytosis in human pancreatic β cells by bth proximal and distal regulatory steps in stimulus-secretion coupling. Diabetes. 1998; 47 (1):57-65.
Ehses JA, Casilla VR, Doty T, Pospisilik JA, Winter KD, Demuth HU, et al. Glucose-dependent insulino-tropic polypeptide promotes β (INS-1) cell survival via cyclic adenosine monophosphate-mediated caspase-3 inhibition and regulation of p38 mitogen-activated protein kinase. Endocrinology. 2003; 144 (10):4433-4445.
Conarello SL, Li Z, Ronan J, Roy RS, Zhu L, Jiang G, et al., Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc Natl Acad Sci USA. 2003; 100 (11): 6825-6830.
Thorens B, Porret A, Buhler L, Deng SP, Morel P, Widmann C. Cloning and functional expression of the human islet GLP1 receptor. Demonstration that exendin-4 is an agonist and exendin 9-39 an antagonist of receptor. Diabetes. 1993; 42 (11): 1678-1682.
Kolterman OG, Kim DD, Shen L, Ruggles JA, Nielsen LL, Fineman MS, et al. Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Syst Pharm. 2005; 62 (2): 173-181.
Nauck MA, Duran S, Kim D, Johns D, Northrup J, Festa A, et al. A comparison of twice daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non inferiority study. Diabetologia. 2007; 50 (2): 259-267.
DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005; 28 (5):1092-1110.
Zinman B, Hoogwerf BJ, Durán-García S, Milton DR, Giaconia JM, Kim DD, et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2007; 146 (7): 477-485.
Agerso H, Jensen LB, Elbrond B, Rolan P, Zdravko-vic M. The pharmacokinetics, pharmaco-dynamics, safety and tolerability of NN2211, a new long-acting GLP1 derivative, in healthy men. Diabetologia. 2002; 45 (2):195-202.
Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007; 298 (2): 194-206.
Garber A, Henrry R, Ratner R, García-Hernández PA, Rodríguez-Pattzi H, Olvera I, et al. Liraglutide versus glimepirine monotherapy for type 2 diabetes (LEAD 3Mono): a randomized, 52 week, phase III, double-blind parallel. Treatment trial. Lancet. 2009; 373 (9662):473-481.
Marre M, et al. Liraglutide plus SU versus TZD plus SU. LEAD 1. Diabetic Medicine 2009;10:
Aschner P, Kipnes MS, Lunceford JK, Sánchez M, Mickel C, Williams-Herman DE. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006; 29 (12): 2632-2637.
Ahren B, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon in type 2 diabetes. J Clin Endocrinol Metab. 2004; 89 (5):2078-2084.
Bergman A, Ebel D, Liu F, Stone J, Wang A, Zeng W, et al. Absolute bioavailability of sitagliptin, an oral dipeptdiylpeptidase-4 inhibitor, in healthy volunteers. Biopharm Drug Dispos. 2007; 2 (6) 8:315-322.
He YL, Sadler BM, Sabo R, Balez S, Wang Y, Campestrini J, et al. The absolute oral bioavailability and population-based pharmacokinetic modeling of a novel dipeptidyl peptidase IV inhibitor, vildagliptin, in healthy volunteers. Clin Pharmacokinet. 2007; 46 (9):787-802.
He YL, Sabo R, Campestrini J, Wang Y, Ligueros-Saylan M, Lasseter KC, et al. The influence of hepatic impairment on the pharmacokinetics of the dipeptidyl peptidase IV inhibitor vildagliptin. Eur J Clin Pharmacol. 2007; 63 (7):677-686.
Charbonnel B, Karasik A, Liu J, Wu M, Meininger G. Sitagliptin Study 019 Group Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care 2006;29(12):2638-2643.
Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P; Sitagliptin Study 019 Group. Efficacy and safety of dipeptidyl peptidase-4 inhibitor, sitagliptin added to ongoing pioglitazona therapy in patients with type 2 diabetes: a 24 week, multicenter, randomized, double blinded, placebo-controlled, parallel group study. Clin Ther. 2006; 28 (19):1556-1568.
Schweizer A, Couturier A, Foley JE, Dejager S. Comparison between vildagliptin and metformin to sustain reductions in HbA(1c) over 1 year in drug-naïve patients with type 2 diabetes. Diabet Med. 2007; 24 (9):955-961.
Bosi E, Camisasca RP, Collober C, Rochoette E, Dejager S. Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin. Diabetes Care. 2007; 30 (4):890-895.
Rosenstock J, Sankoh S, List JF. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drugnaive patients with type 2 diabetes. Diabetes Obes Metab. 2008; 10:376-386.
Jadzinsky M, Pfützner A, Paz-Pacheco E, Xu Z, Allen E, Chen R; CV181-039 Investigators. Saxa-gliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab. 2009; 11:611-622.
Kim D, MacConell L, Zhuang D, Kothare PA, Trautmann M, Fineman M, et al. Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care. 2007; 30 (6):1487-1493.
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