RESUMO
Currently, obesity and its associated complications are considered major public health problems worldwide. Because the causes are multifactorial and complex, different treatment methods are used, which include diet and exercise, as well as the use of drugs, although they can have adverse side effects. A new target for the treatment of obesity may be the incretin system, which consists of hormones that seem to contribute to weight loss. In this sense, some studies have shown a relationship between weight loss and drugs related to incretin system, including glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. The objective of this review is to summarize the association between the incretin system and obesity treatment.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Incretinas/uso terapêutico , Obesidade/tratamento farmacológico , Animais , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/agonistas , Humanos , Incretinas/fisiologia , Obesidade/fisiopatologia , Receptores dos Hormônios Gastrointestinais/agonistas , Receptores dos Hormônios Gastrointestinais/antagonistas & inibidoresRESUMO
Neste artigo descrevemos os mecanismos envolvidos na gênese da hiperglicemia do diabetes mellitus tipo 2. Serão analisadas a resistência insulínica, as características da secreção de insulina, a redução da secreção de insulina, a secreção hepática de glicose, a captação e a secreção hepática de glicose, o aumento da secreção de glucagon e da lipólise e a reabsorção da glicose pelos túbulos renais. Também serão revistos os defeitos das incretinas, a resistência insulínica cerebral e as alterações na flora intestinal.
In this article we describe the mechanisms involved in the genesis of hyperglycemia in type 2 diabetes mellitus. Will be analyzed separately insulin resistance, the characteristics of insulin secretion, the decrease in insulin secretion, the liver's secretion of glucose and hepatic uptake of glucose and glucose reabsorption in the kidney. Also will be review defects of the incretins, cerebral insulin resistance and changes in intestinal flora.
Assuntos
Humanos , Masculino , Feminino , /etiologia , /fisiopatologia , Hiperglicemia/complicações , Ácidos Graxos não Esterificados/farmacologia , Células Secretoras de Insulina , Resistência à Insulina , Incretinas/fisiologia , Insulina , /metabolismoRESUMO
En los últimos años se reconoce un nuevo mecanismo involucrado en la fisiopatología de la Diabetes Mellitus tipo 2: el déficit de producción y/o acción de las incretinas. Las incretinas son enterohormonas que estimulan la secreción de insulina en respuesta a la ingesta de nutrientes. Glucagon like péptido-1 (GLP1) y Polipéptido insulinotrópico glucosa dependiente (GIP) son las principales incretinas descubiertas hasta hoy. Ambas presentan también efecto trófico sobre las células beta de los islotes pancreáticos. GLP-1 presenta otras acciones como son la inhibición de la secreción de glucagón, enlentecimiento del vaciamiento gástrico e inhibición del apetito. Ambas incretinas son rápidamente clivadas por la enzima dipeptidil peptidasa 4 (DPP-4). Nuevas drogas como los incretinomiméticos, análogos y los inhibidores de DPP-4 se presentan como una terapéutica prometedora para los pacientes con diabetes tipo 2.
Two main patophysiological mechanisms are currently involved in Type 2 Diabetes (T2DM), insulin resistance and impairment of beta cell function. However in the last years a new mechanism was reported: a significant decrease in incretins production and or action. Incretins are gut hormones whose main action is stimulating insulin secretion in response to nutrients. The more known incretins are glucagon like peptide-1 (GLP-1) and Gastric insulinothropic peptide (GIP). GLP-1 and GIP not only increase insulin secretion, nor decrease glucagon secretion, slow gastric emptying and reduce apetite generating weight lose. Both incretins are rapidly clived by the enzyme dipeptidil peptidase 4 (DPP4). In order to emulate incretins action, several drugs where developed: agonists of GLP-1 receptors, GLP-1 mimetics, and inhibitors of the DPP4. All of them seems to became a very promise tool for the treatment of T2DM.
Assuntos
Humanos , Masculino , Feminino , Diabetes Mellitus Tipo 2/terapia , Incretinas/fisiologia , Incretinas/uso terapêutico , Polipeptídeo Inibidor Gástrico/fisiologia , Polipeptídeo Inibidor Gástrico/metabolismo , Peptídeo 1 Semelhante ao Glucagon/fisiologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Incretinas/metabolismoRESUMO
In the gastrointestinal tract we produce hormones, called incretins, in response to food ingestion with a direct effect on pancreatic ß and α cell improving the insulin and glucagon response to glucose. The effect consisting in a greater secretion of insulin with a glucose stimulus from the gut or IV injection is called "the incretin effect." The main incretins are: glucagon like peptide-1 (GLP1) and glucose-dependent insulinotropic peptide (GIP). The action of both incretins is very short due to a rapid inhibition in the circulation by an enzyme dipeptylpeptidase IV (DPP4). In type 2 diabetics, the incretin effect is altered and can be improved by elaboration of a GLP1 resistant to the action of DPP4 (GLP1 analogs) or by direct inhibition of DPP4 producing better effect of native GLP1 and GIP. We have exenatide a derivative from exendin 4, and liraglutide very similar to the native human GLP1. Three inhibitors of DPP4: sitagliptin, and vildagliptin and saxagliptin produce a prolonged inhibition of DPP4 and as a consequence increased effect of native incretins with better control of fasting and postprandial glucose and improve on A1c with a very few hypoglycemic events.