Extensive knowledge of diabetes and its complications is helpful to find new drugs for proper treatment to stop degenerative changes derived from this disease. In this context, chrysin (5,7-dihydroxyflavone) is a natural product that occurs in a variety of flowers and fruits with anti-inflammatory and antidiabetic effects, among others. Thus, a diabetic model in athymic nude mice was developed and used to establish the ability of chrysin to decrease the secretion of pro-inflammatory cytokines. Also, it was determined the acute (50 mg/kg) and sub-acute (50 mg/kg/day/10 days) antidiabetic and antihyperlipidemic activities after the period of time treatment. Results indicate that chrysin has significant acute antihyperglycemic and antidiabetic effects in nude diabetic mice (p < 0.05). Moreover, triglyceride blood levels were reduced and IL-1β and TNF-α were diminished after 10 days’ treatment compared with control group (p < 0.05). In conclusion, it was found that chrysin could produce similar effects as metformin, a drug used for the treatment of diabetes, since both test samples decreased glucose and triglycerides levels, they impaired the generation of pro-inflammatory cytokines involved in the development of diabetes and its consequences, such as atherosclerosis and other cardiovascular diseases.

The relationship of uric acid with macrophages has not been fully elucidated. We investigated the effect of uric acid on the proinflammatory ability of human macrophages and then examined the possible molecular mechanism involved. Primary human monocytes were differentiated into macrophages for subsequent exposure to 0, 0.23, 0.45, or 0.9 mmol/L uric acid for 12 h, in the presence or absence of 1 mmol/L probenecid. Flow cytometry was used to measure proinflammatory marker production and phagocytic activity that was quantified as a percentage of GFP-labeled Escherichia coli positive macrophages. qPCR was used to measure the macrophage expression of the urate anion transporter 1 (URAT1). As compared to control cells, the production of tumor necrosis factor-alpha (TNF-alpha), toll-like receptor 4 (TLR4), and cluster of differentiation (CD) 11c was significantly increased by uric acid. In contrast, macrophages expressing CD206, CX3C-motif chemokine receptor 1 (CX3CR1), and C-C chemokine receptor type 2 (CCR2) were significantly reduced. Uric acid progressively increased macrophage phagocytic activity and downregulated URAT1 expression. Probenecid—a non-specific blocker of URAT1-dependent uric acid transport—inhibited both proinflammatory cytokine production and phagocytic activity in macrophages that were exposed to uric acid. These results suggest that uric acid has direct proinflammatory effects on macrophages possibly via URAT1.

Angiotensin II (Ang II) is a critical regulator of insulin signaling in the cardiovascular system and metabolic tissues. However, in adipose cells, the regulatory role of Ang II on insulin actions remains to be elucidated. The effect of Ang II on insulin-induced insulin receptor (IR) phosphorylation, Akt activation, and glucose uptake was examined in 3T3-L1 adipocytes. In these cells, Ang II specifically inhibited insulin-stimulated IR and insulin receptor substrate-1 (IRS-1) tyrosine-phosphorylation, Akt activation, and glucose uptake in a time-dependent manner. These inhibitory actions were associated with increased phosphorylation of the IR at serine residues. Interestingly, Ang II-induced serine-phosphorylation of IRS was not detected, suggesting that Ang II-induced desensitization begins from IR regulation itself. PKC inhibition by BIM I restored the inhibitory effect of Ang II on insulin actions. We also found that Ang II promoted activation of several PKC isoforms, including PKCα/βI/βII/δ, and its association with the IR, particularly PKCβII, showed the highest interaction. Finally, we also found a similar regulatory effect of Ang II in isolated adipocytes, where insulin-induced Akt phosphorylation was inhibited by Ang II, an effect that was prevented by PKC inhibitors. These results suggest that Ang II may lead to insulin resistance through PKC activation in adipocytes.

Non-steroidal anti-inflammatory drugs (NSAIDs) —aspirin, naproxen, nimesulide, and piroxicam— lowered activation of type II cAMP-dependent protein kinase A (PKA-II) in isolated rat adipocytes, decreasing adrenaline- and dibutyryl cAMP (Bt2cAMP)-stimulated lipolysis. The molecular bases of insulin-like actions of NSAID were studied. Based on the reported inhibition of lipolysis by H2O2, catalase was successfully used to block NSAID inhibitory action on Bt2cAMP-stimulated lipolysis. NSAID, at (sub)micromolar range, induced an H2O2 burst in rat adipocyte plasma membranes and in whole adipocytes. NSAID-mediated rise of H2O2 was abrogated in adipocyte plasma membranes by: diphenyleneiodonium, an inhibitor of NADPH oxidase (NOX); the NOX4 antibody; and cytochrome c, trapping the NOX-formed superoxide. These three compounds prevented the inhibition of Bt2cAMP-stimulated lipolysis by NSAIDs. Inhibition of aquaporin-mediated H2O2 transport with AgNO3 in adipocytes allowed NOX activation but prevented the lipolysis inhibition promoted by NSAID: i.e., once synthesized, H2O2 must reach the lipolytic machinery. Since insulin inhibits adrenaline-stimulated lipolysis, the effect of aspirin on isoproterenol-stimulated lipolysis in rat adipocytes was studied. As expected, isoproterenol-mediated lipolysis was blunted by both insulin and aspirin. NSAIDs activate NOX4 in adipocytes to produce H2O2, which impairs cAMP-dependent PKA-II activation, thus preventing isoproterenol-activated lipolysis. H2O2 signaling in adipocytes is a novel and important cyclooxygenase-independent effect of NSAID.

A body mass index (BMI) ≥30 kg/m2 and a waist circumference (WC) ≥80 cm in women (WCF) or ≥90 cm in men (WCM) are reference cardiometabolic risk markers (CMM) for Mexicans adults. However, their reliability to predict other CMM (index tests) in young Mexicans has not been studied in depth. A cross-sectional descriptive study evaluating several anthropometric, physiological and biochemical CMM from 295 young Mexicans was performed. Sensitivity (Se), specificity (Sp) and Youden’s index (J) of reference BMI/WC cutoffs toward other CMM (n = 14) were obtained and their most reliable cutoffs were further calculated at Jmax. Prevalence, incidence and magnitude of most CMM increased along the BMI range (p < 0.01). BMI explained 81 % of WC’s variance [Se (97 %), Sp (71 %), J (68 %), Jmax (86 %), BMI = 30 kg/m2] and 4–50 % of other CMM. The five most prevalent (≥71 %) CMM in obese subjects were high WC, low HDL-C, and three insulin-related CMM [Fasting insulin, HOMA-IR, and QUICKI]. For a BMI = 30 kg/m2, J ranged from 16 % (HDL-C/LDL-C) to 68 % (WC), being moderately reliable (Jmax = 61–67) to predict high uric acid (UA), metabolic syndrome (MetS) and the hypertriglyceridemic-waist phenotype (HTGW). Corrected WCM/WCF were moderate-highly reliable (Jmax = 66–90) to predict HTGW, MetS, fasting glucose and UA. Most CMM were moderate-highly predicted at 27 ± 3 kg/m2 (CI 95 %, 25–28), 85 ± 5 cm (CI 95 %, 82–88) and 81 ± 6cm (CI 95 %, 75–87), for BMI, WCM and WCF, respectively. BMI and WC are good predictors of several CMM in the studied population, although at different cutoffs than current reference values.

The geographical distribution of the metabolic syndrome (MetS) prevalence in young Mexicans (aged 17-24 years) was estimated stepwise starting from its prevalence based on the body mass index (BMI) in a study of 3,176 undergraduate students of this age group from Mexico City. To estimate the number of people with MetS by state, we multiplied its prevalence derived from the BMI range found in the Mexico City sample by the BMI proportions (range and state) obtained from the Mexico 2006 national survey on health and nutrition. Finally, to estimate the total number of young people with MetS in Mexico, its prevalence by state was multiplied by the share of young population in each state according to the National Population and Housing Census 2010. Based on these figures, we estimated the national prevalence of MetS at 15.8%, the average BMI at 24.1 (standard deviation = 4.2), and the prevalence of overweight people (BMI ≥25) of that age group at 39.0%. These results imply that 2,588,414 young Mexicans suffered from MetS in 2010. The Yucatan peninsula in the south and the Sonora state in the north showed the highest rates of MetS prevalence. The calculation of the MetS prevalence by BMI range in a sample of the population, and extrapolating it using the BMI proportions by range of the total population, was found to be a useful approach. We conclude that the BMI is a valuable public health tool to estimate MetS prevalence in the whole country, including its geographical distribution.