Microbial phenolic metabolites improve glucose-stimulated insulin secretion and protect pancreatic beta cells against tert-butyl hydroperoxide-induced toxicity via ERKs and PKC pathways.
Oxidative stress is accepted as one of the causes of beta cell failure in type 2 diabetes. Therefore, identification of natural antioxidant agents that preserve beta cell mass and function is considered an interesting strategy to prevent or treat diabetes. Recent evidences indicated that colonic metabolites derived from flavonoids could possess beneficial effects on various tissues. The aim of this work was to establish the potential anti-diabetic properties of the microbial-derived flavonoid metabolites 3,4-dihydroxyphenylacetic acid (DHPAA), 2,3-dihydroxybenzoic acid (DHBA) and 3-hydroxyphenylpropionic acid (HPPA). To this end, we tested their ability to influence beta cell function and to protect against tert-butyl hydroperoxide-induced beta cell toxicity. DHPAA and HPPA were able to potentiate glucose-stimulated insulin secretion (GSIS) in a beta cell line INS-1E and in rat pancreatic islets. Moreover, pre-treatment of cells with both compounds protected against beta cell dysfunction and death induced by the pro-oxidant. Finally, experiments with pharmacological inhibitors indicate that these effects were mediated by the activation of protein kinase C and the extracellular regulated kinases pathways. Altogether, these findings strongly suggest that the microbial-derived flavonoid metabolites DHPAA and HPPA may have anti-diabetic potential by promoting survival and function of pancreatic beta cells.
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
Elisa
E
Fernández-Millán
Departamento de Metabolismo y Nutrición, Instituto de Ciencia y Tecnología de los Alimentos y Nutrición (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Sonia
S
Ramos
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
Carmen
C
Alvarez
Departamento de Metabolismo y Nutrición, Instituto de Ciencia y Tecnología de los Alimentos y Nutrición (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Laura
L
Bravo
Departamento de Metabolismo y Nutrición, Instituto de Ciencia y Tecnología de los Alimentos y Nutrición (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Luis
L
Goya
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Departamento de Metabolismo y Nutrición, Instituto de Ciencia y Tecnología de los Alimentos y Nutrición (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain. Electronic address: amartina@ictan.csic.es.
María Ángeles
MÁ
Martín
D000818:Animals; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
D007328:Insulin; D010636:Phenols; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose
Dietary polyphenols; INS-1E beta cells; Oxidative stress; Type 2 diabetes mellitus