LPS-Enhanced Glucose-Stimulated Insulin Secretion Is Normalized by Resveratrol.

UNLABELLED:Low-grade inflammation is seen with obesity and is suggested to be a mediator of insulin resistance. The eliciting factor of low-grade inflammation is unknown but increased permeability of gut bacteria-derived lipopolysaccharides (LPS) resulting in endotoxemia could be a candidate. Here we test the effect of LPS and the anti-inflammatory compound resveratrol on glucose homeostasis, insulin levels and inflammation. Mice were subcutaneously implanted with osmotic mini pumps infusing either low-dose LPS or saline for 28 days. Half of the mice were treated with resveratrol delivered through the diet. LPS caused increased inflammation of the liver and adipose tissue (epididymal and subcutaneous) together with enlarged spleens and increased number of leukocytes in the blood. Resveratrol specifically reduced the inflammatory status in epididymal fat (reduced expression of TNFa and Il1b, whereas the increased macrophage infiltration was unaltered) without affecting the other tissues investigated. By LC-MS, we were able to quantitate resveratrol metabolites in epididymal but not subcutaneous adipose tissue. LPS induced insulin resistance as the glucose-stimulated insulin secretion during an oral glucose tolerance test was increased despite similar plasma glucose level resulting in an increase in the insulinogenic index (IGI; delta0-15insulin/delta0-15glucose) from 13.73 to 22.40 pmol/mmol (P < 0.001). This aberration in insulin and glucose homeostasis was normalized by resveratrol. IN CONCLUSION:Low-dose LPS enhanced the glucose-stimulated insulin secretion without affecting the blood glucose suggesting increased insulin resistance. Resveratrol restored LPS-induced alteration of the insulin secretion and demonstrated anti-inflammatory effects specifically in epididymal adipose tissue possibly due to preferential accumulation of resveratrol metabolites pointing towards a possible important involvement of this tissue for the effects on insulin resistance and insulin secretion

Le Scienze della Terra: Didattica e Laboratorio di Didattica. Riflessioni metodologico-disciplinari

Riflessioni metodologico-disciplinari sull'insegnamento della Didattica e del Laboratorio di Didattica delle Scienze della Terra per docenti in formazione e in servizio nella Scuola Secondaria di 2\ub0 grado

Effect of resveratrol and/or LPS on adiponectin expression.

<p>(A) Adiponectin expression was measured by qPCR analysis in epididymal and subcutaneous adipose tissue (n = 9–10 per group). (B) Plasma values of adiponectin (n = 9–10 per group). Data are presented as means ± SEM. *P < 0.05, **P < 0.01 according to unpaired t-test.</p

LPS induce enhanced GSIS and is reversed by resveratrol.

<p>(A) Oral glucose tolerance test (OGTT) in mice treated with LPS and/or resveratrol (n = 13–14 per group). (B) Area under the curve of (A) for each treatment group. (C) Insulin concentrations 0 and 15 minutes after oral administration of a glucose dose (n = 12–15 per group). (D) The insulinogenic index (delta_0-15Insulin/delta_0-15Glucose) was calculated for each treatment group (n = 12–15). Data are presented as means ± SEM. Means with different superscript letters are significantly different at P < 0.05 according to post-hoc ANOVA.</p

Resveratrol only reduces LPS-induced inflammation in epididymal adipose tissue.

<p>(A) Total leukocyte count of whole blood in mice treated with LPS and/or resveratrol (n = 10 per group). (B) Spleen weights as percentage of body weight (n = 10 per group). (C, D, E) qPCR analyses of gene expression of the pro-inflammatory cytokines TNFa, Il1b and the macrophage marker CD14 in liver (C; n = 8–10 per group), subcutaneous (D; n = 10 per group) and epididymal adipose tissue (E; 7–10 per group) and skeletal muscle (F; n = 9–10 per group). Data are presented as means ± SEM. Means with different superscript letters are significantly different at P < 0.05 according to post-hoc ANOVA.</p