ピオグリタゾン ニヨル マクロファージ ゾウショク ヨクセイ コウカ オ カイシタ ドウミャク コウカ シンテン ヨクセイ コウカ ノ ケントウ

博士(医学)熊本大

Impact of tissue macrophage proliferation on peripheral and systemic insulin resistance in obese mice with diabetes

Introduction Obesity-related insulin resistance is a widely accepted pathophysiological feature in type 2 diabetes. Systemic metabolism and immunity are closely related, and obesity represents impaired immune function that predisposes individuals to systemic chronic inflammation. Increased macrophage infiltration and activation in peripheral insulin target tissues in obese subjects are strongly related to insulin resistance. Using a macrophage-specific proliferation inhibition mouse model (mac-p27Tg), we previously reported that suppressed plaque inflammation reduced atherosclerosis and improved plaque stabilization. However, the direct evidence that proliferating macrophages are responsible for inducing insulin resistance was not provided.Research design and methods The mac-p27Tg mice were fed a high-fat diet, and glucose metabolism, histological changes, macrophage polarization, and tissue functions were investigated to reveal the significance of tissue macrophage proliferation in insulin resistance and obesity.Results The mac-p27Tg mice showed improved glucose tolerance and insulin sensitivity, along with a decrease in the number and ratio of inflammatory macrophages. Obesity-induced inflammation and oxidative stress was attenuated in white adipose tissue, liver, and gastrocnemius. Histological changes related to insulin resistance, such as liver steatosis/fibrosis, adipocyte enlargement, and skeletal muscle fiber transformation to fast type, were ameliorated in mac-p27Tg mice. Serum tumor necrosis factor alpha and free fatty acid were decreased, which might partially impact improved insulin sensitivity and histological changes.Conclusions Macrophage proliferation in adipose tissue, liver, and skeletal muscle was involved in promoting the development of systemic insulin resistance. Controlling the number of tissue macrophages by inhibiting macrophage proliferation could be a therapeutic target for insulin resistance and type 2 diabetes

Pictavia Aurea

Este volumen, titulado Pictavia aurea, reúne 131 estudios que constituyen una granada muestra de los debates y las presentaciones en torno a la cultura hispánica del Siglo de Oro que entre los días 11 y 15 de julio de 2011 se dieron en la ciudad de Poitiers (Francia) en el marco del IX congreso de la Asociación Internacional “Siglo de Oro”. Auspiciada por la Universidad de Poitiers, a través del Centro de Estudios de la Literatura española de Entre Siglos (siglos xvii-xviii) (CELES XVII-XVIII) y el laboratorio «Formes et Représentations en Linguistique et Littérature» (FoReLL), la convocatoria reunió en la ciudad francesa a 276 participantes y a un centenar de asistentes en la novena edición del Congreso de la Asociación, que celebró entonces la efeméride del 450o aniversario del nacimiento de Luis de Góngora.A Isaías Lerner, maestro de la filología hispánic