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Cell Metab ; 27(6): 1201-1211.e3, 2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29731416

RESUMO

Gastric emptying is a critical regulator of postprandial glucose and delayed gastric emptying is an important mechanism of improved glycemic control achieved by short-acting glucagon-like peptide-1 (GLP-1) analogs in clinical practice. Here we report on a novel regulatory mechanism of gastric emptying in humans. We show that increasing interleukin (IL)-6 concentrations delays gastric emptying leading to reduced postprandial glycemia. IL-6 furthermore reduces insulin secretion in a GLP-1-dependent manner while effects on gastric emptying are GLP-1 independent. Inhibitory effects of IL-6 on gastric emptying were confirmed following exercise-induced increases in IL-6. Importantly, gastric- and insulin-reducing effects were maintained in individuals with type 2 diabetes. These data have clinical implications with respect to the use of IL-6 inhibition in autoimmune/inflammatory disease, and identify a novel target that could be exploited pharmacologically to delay gastric emptying and spare insulin, which may be beneficial for the beta cell in type 2 diabetes.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Esvaziamento Gástrico/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hipoglicemia/metabolismo , Secreção de Insulina/efeitos dos fármacos , Interleucina-6/farmacologia , Proteínas Recombinantes/farmacologia , Idoso , Estudos de Casos e Controles , Método Duplo-Cego , Exercício Físico , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Interleucina-6/administração & dosagem , Masculino , Proteínas Recombinantes/administração & dosagem , Adulto Jovem
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