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1.
Mol Nutr Food Res ; 60(4): 846-57, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27061233

RESUMEN

SCOPE: Trans-11 vaccenic acid (VA) is a fatty acid produced by ruminants entering the human food supply through meat and dairy products, which appears not to have the health risks associated with industrially produced trans-fatty acids. In this study, we investigated the effect of VA on insulin secretion in vivo in rats and in vitro in human and rat islets after diabetogenic insult. METHODS AND RESULTS: Hyperglycemic clamp showed that VA dietary supplementation for 8 weeks significantly increased glucose turnover in rats with type 2 diabetes (T2D), accompanied by an elevated plasma C-peptide concentration, indicating improved insulin secretion. The ß-cell area and proliferation rate were higher in T2D+VA than T2D group. Isolated islets from T2D+VA rats had higher glucose-stimulated insulin secretion (GSIS) than T2D group. In vitro, VA treatment for 24 and 48 h significantly enhanced GSIS in rat and human islets after diabetogenic challenges. The mRNA expression of G-protein-coupled receptor 40 (GPR40) and regenerating islet-derived 1α (REG-1α) were consistently increased by VA in both rat and human islets. CONCLUSION: These results indicate that VA may improve insulin secretion and growth of islets in T2D, at least partly by altering GPR40 and REG-1α mRNA expression.


Asunto(s)
Diabetes Mellitus Tipo 2/dietoterapia , Insulina/metabolismo , Ácidos Oléicos/farmacología , Anciano , Animales , Proliferación Celular/efectos de los fármacos , Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos , Glucosa/metabolismo , Humanos , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Masculino , Persona de Mediana Edad , Ácidos Oléicos/sangre , Ácido Palmítico/farmacología , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Tacrolimus/farmacología
2.
Xenotransplantation ; 23(1): 3-13, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26940725

RESUMEN

The International Xenotransplantation Association has updated its original "Consensus Statement on Conditions for Undertaking Clinical Trials of Porcine Islet Products in Type 1 Diabetes," which was published in Xenotransplantation in 2009. This update is timely and important in light of scientific progress and changes in the regulatory framework pertinent to islet xenotransplantation. Except for the chapter on "informed consent," which has remained relevant in its 2009 version, all other chapters included in the initial consensus statement have been revised for inclusion in this update. These chapters will not provide complete revisions of the original chapters; rather, they restate the key points made in 2009, emphasize new and under-appreciated topics not fully addressed in 2009, suggest relevant revisions, and communicate opinions that complement the consensus opinion. Chapter 1 provides an update on national regulatory frameworks addressing xenotransplantation. Chapter 2 a, previously Chapter 2, suggests several important revisions regarding the generation of suitable source pigs from the perspective of the prevention of xenozoonoses. The newly added Chapter 2b discusses conditions for the use of genetically modified source pigs in clinical islet xenotransplantation. Chapter 3 reviews porcine islet product manufacturing and release testing. Chapter 4 revisits the critically important topic of preclinical efficacy and safety data required to justify a clinical trial. The main achievements in the field of transmission of all porcine microorganisms, the rationale for more proportionate recipient monitoring, and response plans are reviewed in Chapter 5. Patient selection criteria and circumstances where trials of islet xenotransplantation would be both medically and ethically justified are examined in Chapter 6 in the context of recent advances in available and emerging alternative therapies for serious and potentially life-threatening complications of diabetes. It is hoped that this first update of the International Xenotransplantation Association porcine islet transplant consensus statement will assist the islet xenotransplant scientific community, sponsors, regulators, and other stakeholders actively involved in the clinical translation of islet xenotransplantation.


Asunto(s)
Diabetes Mellitus Tipo 1/cirugía , Consentimiento Informado/legislación & jurisprudencia , Trasplante de Islotes Pancreáticos/legislación & jurisprudencia , Publicaciones Periódicas como Asunto , Trasplante Heterólogo/legislación & jurisprudencia , Animales , Ensayos Clínicos como Asunto , Humanos , Selección de Paciente , Porcinos
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