Adipose tissue inflammation and reduced pancreatic β-cell function are key issues in the development of cardiovascular disease and progressive metabolic dysfunction in type 2 diabetes mellitus. The aim of this study was to determine the effect of the DPP IV inhibitor sitagliptin on adipose tissue and pancreatic islet inflammation in a diet-induced obesity model. C57Bl/6J mice were placed on a high-fat (60% kcal fat) diet for 12 wk, with or without sitagliptin (4 g/kg) as a food admix. Sitagliptin significantly reduced fasting blood glucose by 21% as well as insulin by ∼25%. Sitagliptin treatment reduced body weight without changes in overall body mass index or in the epididymal and retroperitoneal fat mass. However, sitagliptin treatment led to triple the number of small adipocytes despite reducing the number of the very large adipocytes. Sitagliptin significantly reduced inflammation in the adipose tissue and pancreatic islet. Macrophage infiltration in adipose tissue evaluated by immunostaining for Mac2 was reduced by sitagliptin ( P < 0.01), as was the percentage of CD11b+/F4/80+ cells in the stromal vascular fraction ( P < 0.02). Sitagliptin also reduced adipocyte mRNA expression of inflammatory genes, including IL-6, TNFα, IL-12(p35), and IL-12(p40), 2.5- to fivefold as well as 12-lipoxygenase protein expression. Pancreatic islets were isolated from animals after treatments. Sitagliptin significantly reduced mRNA expression of the following inflammatory cytokines: MCP-1 (3.3-fold), IL-6 (2-fold), IL-12(p40) (2.2-fold), IL-12(p35) (5-fold, P < 0.01), and IP-10 (2-fold). Collectively, the results indicate that sitagliptin has anti-inflammatory effects in adipose tissue and in pancreatic islets that accompany the insulinotropic effect.

Adipose tissue inflammation in obesity is a major factor leading to cardiovascular disease and type 2 diabetes.12/15 lipoxygenases (ALOX) play an important role in the generation of inflammatory mediators, insulin resistance and downstream immune activation in animal models of obesity. However, the expression and roles of 12/15ALOX isoforms, and their cellular sources in human subcutaneous (sc) and omental (om) fat in obesity is unknown. The objective of this study was to examine the gene expression and localization of ALOX isoforms and relevant downstream cytokines in subcutaneous (sc) and omental (om) adipose tissue in obese humans. Paired biopsies of sc and om fat were obtained during bariatric surgeries from 24 morbidly obese patients. Gene and protein expression for ALOX15a, ALOX15b and ALOX 12 were measured by real-time PCR and western blotting in adipocytes and stromal vascular fractions (SVF) from om and sc adipose tissue along with the mRNA expression of the downstream cytokines IL-12a, IL-12b, IL-6, IFNγ and the chemokine CXCL10. In a paired analysis, all ALOX isoforms, IL-6, IL-12a and CXCL10 were significantly higher in om vs. sc fat. ALOX15a mRNA and protein expression was found exclusively in om fat. All of the ALOX isoforms were expressed solely in the SVF. Further fractionation of the SVF in CD34+ and CD34-cells indicated that ALOX15a is predominantly expressed in the CD34+ fraction including vascular and progenitor cells, while ALOX15B is mostly expressed in the CD34-cells containing various leucocytes and myeloid cells. This result was confirmed by immunohistochemistry showing exclusive localization of ALOX15a in the om fat and predominantly in the vasculature and non-adipocyte cells. Our finding is identifying selective expression of ALOX15a in human om but not sc fat. This is a study showing a major inflammatory gene exclusively expressed in visceral fat in humans.

Oxidation of B-phase plutonium was studied by hot-stage x-ray diffraction, microtopography, and thermogravimetry. The oxidation process was found initially to proceed by the formation of a protective sesquioxide film. Subsequently, the protective film was destroyed by blistering and the reaction rate accelerated.Plutonium is very susceptible to oxidation. The mechanisms involved in this oxidation are complicated by the existence of six temperature-dependent allotropic modifications of the metal and a rather complex metal-oxygen relationship (1). Of the six metallic phases, the low-temperature a-phase which is stable to 112~ has received the most attention (2-8). Under conditions of low humidity, oxidation of the a-phase appears to follow a parabolic rate law. Sackman (4) observed a series of successive parabolic weight gain curves when the reaction was allowed to proceed for extended periods of time. This behavior was thought to arise from the continued failure and regrowth of a protective sesquioxide film.Few in-depth investigations of the reactions of higher temperature metallic phases with oxygen have been made. Schnizlein and Fischer (9), in investigating the oxidation process above 140~ reported paralinear kinetics through the B (112~176 ~/ (185 ~ 310~and 5 (310~176 phases. The paralinear model involves the simultaneous production of a protective inner film and an outer porous layer. Thompson (10) observed two linear stages of oxidation in the #-phase with paralinear kinetics being followed only in the-/-and 6-phases.Both Thompson and Schnizlein observed a reduction in the rate of oxidation of 5-phase metal at about 400~ Thompson (10) and Vesterberg and Ekbom (11) reported an additional rate reduction occurring in the B-phase at about 160~The present study was designed to investigate reaction mechanisms and kinetics associated with the oxidation of B-phase plutonium. Special attention was given to the relationship between the reaction rate, types of oxides formed, and microtopography of the resulting oxide products. Kinetic data were obtained by thermogravimetry. The types of oxides produced and the exterior oxide surface characteristics were followed by hot-stage x-ray diffraction and microscopy using conditions duplicating those in the rate studies. Experimental Material and ProceduresMateriaL--Very pure electrorefined plutonium metal was used in the kinetic and mechanistic investigations. The electrorefined button was cast into an ingot and hot-rolled in the B-phase to a thickness of 0.018 in. Impurities in the resulting sheet are listed in Table I. Procedures.--Isothermal oxidation experiments were conducted with fresh polished samples. The samples were given a final finish with dry jeweler's rouge. The oxidation was followed thermogravimetrically on a Mettler I Thermoanalyzer enclosed in a glove box. The atmosphere used in the investigation was a 20% O2-80% Ar mixture. Moisture was removed to less than 10 ppm by volume by passing the gas over a molecular sieve desiccant. Moisture levels were determined ...

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Recently in conversation with a Brazilian doctor, Inspector of Ports for his Government, I asked him regarding the etiology of beriberi. He replied that the disease is due to the deficiency or absence of vit~mines in diet, and especially in rice, so much so that steps were being taken to prohibit the importation of polished rice into the country. Questioned as to the disease known as beriberi in Matto Grosso and the Amazons, he replied that it is quite a different disease, be,ng a "quinine-resisting form of paludism." Whether or not this represents the official theory of the Brazilian authorities I have not been able to ascertain. My own observations, however, and information obtained fr°m vari°us other sources, may be of sufficient interest as to merit consideration from those whose special work it is to investigate the etiology of such diseases.

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Die Oxidation von β‐Pu wird durch Röntgenbeugungsmessungen, Mikrotopographie und Thermogravirnetrie untersucht.