In vivo and ex vivo regulation of visfatin production by leptin in human and murine adipose tissue : role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways

Visfatin is an adipogenic adipokine with increased levels in obesity, properties common to leptin. Thus, leptin may modulate visfatin production in adipose tissue (AT). Therefore, we investigated the effects of leptin on visfatin levels in 3T3-L1 adipocytes and human/murine AT, with or without a leptin antagonist. The potential signaling pathways and mechanisms regulating visfatin production in AT was also studied. Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of visfatin. ELISA was performed to measure visfatin levels in conditioned media of AT explants, and small interfering RNA technology was used to reduce leptin receptor expression. Leptin significantly (P < 0.01) increased visfatin levels in human and murine AT with a maximal response at leptin 10–9 M, returning to baseline at leptin 10–7 M. Importantly, ip leptin administration to C57BL/6 ob/ob mice further supported leptin-induced visfatin protein production in omental AT (P < 0.05). Additionally, soluble leptin receptor levels rose with concentration dependency to a maximal response at leptin 10–7 M (P < 0.01). The use of a leptin antagonist negated the induction of visfatin and soluble leptin receptor by leptin. Furthermore, leptin-induced visfatin production was significantly decreased in the presence of MAPK and phosphatidylinositol 3-kinase inhibitors. Also, when the leptin receptor gene was knocked down using small interfering RNA, leptin-induced visfatin expression was significantly decreased. Thus, leptin increases visfatin production in AT in vivo and ex vivo via pathways involving MAPK and phosphatidylinositol 3-kinase signaling. The pleiotropic effects of leptin may be partially mediated by visfatin

Political Theory, Political Science, And The End Of Civic Engagement

Within a span of fifteen years civic engagement has become a cottage industry in political science and political theory, but the term has now outlived its usefulness and exemplifies Giovanni Sartori\u27s worry about conceptual stretching. This article traces civic engagement\u27s ascension as a catch-all term for almost anything that citizens might happen to do together or alone, and illustrates the confusion that its popularity has occasioned. It proposes that civic engagement meet a well-deserved end, to be replaced with a more nuanced and descriptive set of engagements: political, social, and moral. It also examines the appeal of engagement itself, a term that entails both attention and energy. Attention and energy are the mainsprings of politics and most other challenging human endeavors. But they can be invested politically, or in associative pursuits, or in moral reasoning and follow-through, and those types of engagement can, but need not, coincide. We should be asking which kinds of engagement-which kinds of attention and energetic activity-make democracy work, and how they might be measured and promoted

Étudiant(e)s de niveau collégial ayant des incapacités College students with disabilities

"La présente recherche a été subventionnée par le Ministère de l'éducation dans le cadre du Programme d'aide à la recherche sur l'enseignement et l'apprentissage (PAREA)"Titre de l'écran-titre (visionné le 8 déc. 2006)Également disponible en version papierBibliogr

Analysis of two-player quantum games in an EPR setting using geometric algebra

The framework for playing quantum games in an Einstein-Podolsky-Rosen (EPR) type setting is investigated using the mathematical formalism of Clifford geometric algebra (GA). In this setting, the players' strategy sets remain identical to the ones in the classical mixed-strategy version of the game, which is then obtained as proper subset of the corresponding quantum game. As examples, using GA we analyze the games of Prisoners' Dilemma and Stag Hunt when played in the EPR type setting.Comment: 20 pages, no figure, revise

N-player quantum games in an EPR setting

The $N$-player quantum game is analyzed in the context of an Einstein-Podolsky-Rosen (EPR) experiment. In this setting, a player's strategies are not unitary transformations as in alternate quantum game-theoretic frameworks, but a classical choice between two directions along which spin or polarization measurements are made. The players' strategies thus remain identical to their strategies in the mixed-strategy version of the classical game. In the EPR setting the quantum game reduces itself to the corresponding classical game when the shared quantum state reaches zero entanglement. We find the relations for the probability distribution for $N$-qubit GHZ and W-type states, subject to general measurement directions, from which the expressions for the mixed Nash equilibrium and the payoffs are determined. Players' payoffs are then defined with linear functions so that common two-player games can be easily extended to the $N$-player case and permit analytic expressions for the Nash equilibrium. As a specific example, we solve the Prisoners' Dilemma game for general $N \ge 2$. We find a new property for the game that for an even number of players the payoffs at the Nash equilibrium are equal, whereas for an odd number of players the cooperating players receive higher payoffs.Comment: 26 pages, 2 figure

Effects of sample handling methods on substance P concentrations and immunoreactivity in bovine blood samples

Objective—To determine the effects of protease inhibitors and holding times and temperatures before processing on the stability of substance P in bovine blood samples. Samples—Blood samples obtained from a healthy 6-month-old calf. Procedures—Blood samples were dispensed into tubes containing exogenous substance P and 1 of 6 degradative enzyme inhibitor treatments: heparin, EDTA, EDTA with 1 of 2 concentrations of aprotinin, or EDTA with 1 of 2 concentrations of a commercially available protease inhibitor cocktail. Plasma was harvested immediately following collection or after 1, 3, 6, 12, or 24 hours of holding at ambient (20.3° to 25.4°C) or ice bath temperatures. Total substance P immunoreactivity was determined with an ELISA; concentrations of the substance P parent molecule, a metabolite composed of the 9 terminal amino acids, and a metabolite composed of the 5 terminal amino acids were determined with liquid chromatography–tandem mass spectrometry. Results—Regarding blood samples processed immediately, no significant differences in substance P concentrations or immunoreactivity were detected among enzyme inhibitor treatments. In blood samples processed at 1 hour of holding, substance P parent molecule concentration was significantly lower for ambient temperature versus ice bath temperature holding conditions; aprotinin was the most effective inhibitor of substance P degradation at the ice bath temperature. The ELISA substance P immunoreactivity was typically lower for blood samples with heparin versus samples with other inhibitors processed at 1 hour of holding in either temperature condition. Conclusions and Clinical Relevance—Results suggested that blood samples should be chilled and plasma harvested within 1 hour after collection to prevent substance P degradation

Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi[S]

Angiopoietin-like protein 3 (ANGPTL3) inhibits lipid clearance and is a promising target for managing cardiovascular disease. Here we investigated the effects of a high-sugar (high-fructose) diet on circulating ANGPTL3 concentrations in rhesus macaques. Plasma ANGPTL3 concentrations increased ∼30% to 40% after 1 and 3 months of a high-fructose diet (both P &lt; 0.001 vs. baseline). During fructose-induced metabolic dysregulation, plasma ANGPTL3 concentrations were positively correlated with circulating indices of insulin resistance [assessed with fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR)], hypertriglyceridemia, adiposity (assessed as leptin), and systemic inflammation [C-reactive peptide (CRP)] and negatively correlated with plasma levels of the insulin-sensitizing hormone adropin. Multiple regression analyses identified a strong association between circulating APOC3 and ANGPTL3 concentrations. Higher baseline plasma levels of both ANGPTL3 and APOC3 were associated with an increased risk for fructose-induced insulin resistance. Fish oil previously shown to prevent insulin resistance and hypertriglyceridemia in this model prevented increases of ANGPTL3 without affecting systemic inflammation (increased plasma CRP and interleukin-6 concentrations). ANGPTL3 RNAi lowered plasma concentrations of ANGPTL3, triglycerides (TGs), VLDL-C, APOC3, and APOE. These decreases were consistent with a reduced risk of atherosclerosis. In summary, dietary sugar-induced increases of circulating ANGPTL3 concentrations after metabolic dysregulation correlated positively with leptin levels, HOMA-IR, and dyslipidemia. Targeting ANGPTL3 expression with RNAi inhibited dyslipidemia by lowering plasma TGs, VLDL-C, APOC3, and APOE levels in rhesus macaques

17β-Estradiol Treatment Improves Acetylcholine-Induced Relaxation of Mesenteric Arteries in Ovariectomized UC Davis Type 2 Diabetes Mellitus Rats in Prediabetic State

We recently reported sex differences in mesenteric arterial function of the UC Davis type-2 diabetes mellitus (UCD-T2DM) rats as early as the prediabetic state. We reported that mesenteric arteries (MA) from prediabetic male rats exhibited a greater impairment compared to that in prediabetic females. However, when females became diabetic, they exhibited a greater vascular dysfunction than males. Thus, the aim of this study was to investigate whether the female sex hormone, estrogen preserves mesenteric arterial vasorelaxation in UCD-T2DM female rats at an early prediabetic state. Age-matched female Sprague Dawley and prediabetic (PD) UCD-T2DM rats were ovariectomized (OVX) and subcutaneously implanted with either placebo or 17β-estradiol (E2, 1.5 mg) pellets for 45 days. We assessed the contribution of endothelium-derived relaxing factors (EDRF) to acetylcholine (ACh)-induced vasorelaxation, using pharmacological inhibitors. Responses to sodium nitroprusside (SNP) and phenylephrine (PE) were also measured. Additionally, metabolic parameters and expression of some targets associated with vascular and insulin signaling were determined. We demonstrated that the responses to ACh and SNP were severely impaired in the prediabetic state (PD OVX) rats, while E2 treatment restored vasorelaxation in the PD OVX + E2. Moreover, the responses to PE was significantly enhanced in MA of PD OVX groups, regardless of placebo or E2 treatment. Overall, our data suggest that 1) the impairment of ACh responses in PD OVX rats may, in part, result from the elevated contractile responses to PE, loss of contribution of endothelium-dependent hyperpolarization (EDH) to vasorelaxation, and a decreased sensitivity of MA to nitric oxide (NO), and 2) the basis for the protective effects of E2 may be partly attributed to the elevation of the NO contribution to vasorelaxation and its interaction with MA as well as potential improvement of insulin signaling. Here, we provide the first evidence of the role of E2 in protecting MA from early vascular dysfunction in prediabetic female rats

Moringa Isothiocyanate-rich Seed Extract Delays the Onset of Diabetes in UC Davis Type-2 Diabetes Mellitus Rats

Moringa seeds have been used traditionally in the management of type 2 diabetes mellitus (T2DM) and contain potent bioactive isothiocyanates. This study evaluated the efficacy of an isothiocyanate-rich moringa seed extract in delaying the onset of T2DM in UC Davis T2DM rats, a well validated model which closely mimics T2DM in humans. Rats were separated into three groups; control, moringa seed extract at 0.4%, and a weight matched group. Rats were fed respective diets for 8 months, during which energy intake, body weight, the onset of diabetes circulating hormones, metabolites and markers of inflammation and liver function, and were monitored. The MS group had a significantly slower rate of diabetes onset p = 0.027), lower plasma glucose (p = 0.043), and lower HbA1c (p = 0.008) compared with CON animals. There were no significant differences in food intake and body weight between all groups. This study demonstrated MS can delay the onset of diabetes in the UC Davis T2DM rat model to a greater extent than moderate caloric restriction (by comparison to the WM group). The results support its documented traditional uses and a bioactive role of moringa isothiocyanates and suggest the potential efficacy for moringa supplementation for diabetes management in populations at risk for T2DM

Using HbA1c to Diagnose Diabetes in the UC, Davis-Type 2 Diabetes Mellitus Rat Model

With disease progression, type 2 diabetes mellitus (T2DM) leads to debilitating complications arising from damage to nerves and blood vessels. Importantly, investigations focusing on T2DM progression have the capacity to distinguish individuals at greater risk for these severe complications through the identification of predictive biomarkers. Hence, the accurate diagnosis of T2DM is critical to such investigations. UC Davis (UCD) T2DM rats are born without diabetes and develop the disease over time with a similar pathophysiology to that in humans. This unique rat model allows researchers to investigate predictive biomarkers linked to the progression of T2D; however, such investigations require an accurate diagnosis of T2DM onset. PURPOSE: To determine the most accurate measure to diagnose T2DM using UCD-T2DM rats. METHODS: 10 male UCD-T2DM rats were used in this study. Glucose and HbA1c were measured weekly from the tail beginning at 16 wks of age (before onset) and continuing until 25 wks of age (all rats had become diabetic). These measures were taken under both fasted (8 hrs) and random conditions as well as in the morning (AM) and afternoon (PM). A two-way repeated measures ANOVA was run with condition [fasted (FG) vs random (RG)] and time (AM vs PM) as factors, followed by Holm Sidak post hoc analyses. In addition, growth curves were fit to the data for all rats to estimate the trajectories of RG and HbA1c. RESULTS: We found that RG was more variable compared to FG (FG: 116±46 vs RG: 216±94 mg/dL; n=10). However, HbA1c was stable across both conditions (fasted HbA1c: 6.0±0.8 vs random HbA1c: 6.0±1.0%; n=10). In addition, both FG and RG morning levels were significantly lower compared to afternoon (FG AM: 99±6 vs FG PM: 133±19 mg/dL; n=10; p0.05). In addition, the location on the growth curve where RG crossed 200 mg/dL (currently the most common diagnostic criteria used) corresponded to a HbA1c of 5.6%. CONCLUSION: A HbA1c of 5.6% may provide a more accurate measure to diagnose the onset of diabetes in the UCD-T2DM rat model