Increased Adiposity, Dysregulated Glucose Metabolism and Systemic Inflammation in Galectin-3 KO Mice

PMCID: PMC3579848This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The inflammasome in chronic complications of diabetes and related metabolic disorders

Diabetes mellitus (DM) ranks seventh as a cause of death worldwide. Chronic complications, including cardiovascular, renal, and eye disease, as well as DM-associated non-alcoholic fatty liver disease (NAFLD) account for most of the morbidity and premature mortality in DM. Despite continuous improvements in the management of late complications of DM, significant gaps remain. Therefore, searching for additional strategies to prevent these serious DM-related conditions is of the utmost importance. DM is characterized by a state of low-grade chronic inflammation, which is critical in the progression of complications. Recent clinical trials indicate that targeting the prototypic pro-inflammatory cytokine interleukin-1β (IL-1 β) improves the outcomes of cardiovascular disease, which is the first cause of death in DM patients. Together with IL-18, IL-1β is processed and secreted by the inflammasomes, a class of multiprotein complexes that coordinate inflammatory responses. Several DM-related metabolic factors, including reactive oxygen species, glyco/lipoxidation end products, and cholesterol crystals, have been involved in the pathogenesis of diabetic kidney disease, and diabetic retinopathy, and in the promoting effect of DM on the onset and progression of atherosclerosis and NAFLD. These metabolic factors are also well-established danger signals capable of regulating inflammasome activity. In addition to presenting the current state of knowledge, this review discusses how the mechanistic understanding of inflammasome regulation by metabolic danger signals may hopefully lead to novel therapeutic strategies targeting inflammation for a more effective treatment of diabetic complications

Diabetes and pancreatic cancer-a dangerous liaison relying on carbonyl stress

Both type 2 (T2DM) and type 1 (T1DM) diabetes mellitus confer an increased risk of pancreatic cancer in humans. The magnitude and temporal trajectory of the risk conferred by the two forms of diabetes are similar, suggesting a common mechanism. Carbonyl stress is a hallmark of hyperglycemia and dyslipidemia, which accompanies T2DM, prediabetes, and obesity. Accumulating evidence demonstrates that diabetes promotes pancreatic ductal adenocarcinoma (PDAC) in experimental models of T2DM, a finding recently confirmed in a T1DM model. The carbonyl stress markers advanced glycation end-products (AGEs), the levels of which are increased in diabetes, were shown to markedly accelerate tumor development in a mouse model of Kras-driven PDAC. Consistently, inhibition of AGE formation by trapping their carbonyl precursors (i.e., reactive carbonyl species, RCS) prevented the PDAC-promoting effect of diabetes. Considering the growing attention on carbonyl stress in the onset and progression of several cancers, including breast, lung and colorectal cancer, this review discusses the mechanisms by which glucose and lipid imbalances induce a status of carbonyl stress, the oncogenic pathways activated by AGEs and their precursors RCS, and the potential use of carbonyl-scavenging agents and AGE inhibitors in PDAC prevention and treatment, particularly in high-risk diabetic individuals

Diabetic complications and oxidative stress: A 20‐year voyage back in time and back to the future

Twenty years have passed since Brownlee and colleagues proposed a single unifying mechanism for diabetic complications, introducing a turning point in this field of research. For the first time, reactive oxygen species (ROS) were identified as the causal link between hyperglycemia and four seemingly independent pathways that are involved in the pathogenesis of diabetes-associated vascular disease. Before and after this milestone in diabetes research, hundreds of articles describe a role for ROS, but the failure of clinical trials to demonstrate antioxidant benefits and some recent experimental studies showing that ROS are dispensable for the pathogenesis of diabetic complications call for time to reflect. This twenty‐year journey focuses on the most relevant literature regarding the main sources of ROS generation in diabetes and their role in the pathogenesis of cell dysfunction and diabetic complications. To identify future research directions, this review discusses the evidence in favor and against oxidative stress as an initial event in the cellular biochemical abnormalities induced by hyperglycemia. It also explores possible alternative mechanisms, including carbonyl stress and the Warburg effect, linking glucose and lipid excess, mitochondrial dysfunction, and the activation of alternative pathways of glucose metabolism leading to vascular cell injury and inflammation

Sopra- o sovra-? E dopo si raddoppia?

Le parole prefissate con sopra- / sovra- suscitano in molti lettori dubbi sulla preferenza da accordare all’una o all’altra forma del prefisso e al loro impiego con o senza raddoppiamento in parole quali: sopralluogo / sovralluogo, soprastante / sovrastante, sopracitato / sopraccitato / sovracitato / sovraccitato, soprannumerario / sovrannumerario, soprascrivere / sovrascrivere; altre domande riguardano l’esistenza o l’ammissibilità di alcune parole, tra cui soprastimare, sovralzo

Renal expression and localization of the receptor for (Pro)renin and its ligands in rodent models of diabetes, metabolic syndrome, and age-dependent focal and segmental glomerulosclerosis

The (pro)renin receptor ((P)RR), a versatile protein found in various organs, including the kidney, is implicated in cardiometabolic conditions like diabetes, hypertension, and dyslipidemia, potentially contributing to organ damage. Importantly, changes in (pro)renin/(P)RR system localization during renal injury, a critical information base, remain unexplored. This study investigates the expression and topographic localization of the full length (FL)-(P)RR, its ligands (renin and prorenin), and its target cyclooxygenase-2 and found that they are upregulated in three distinct animal models of renal injury. The protein expression of these targets, initially confined to specific tubular renal cell types in control animals, increases in renal injury models, extending to glomerular cells. (P)RR gene expression correlates with protein changes in a genetic model of focal and segmental glomerulosclerosis. However, in diabetic and high-fat-fed mice, (P)RR mRNA levels contradict FL-(P)RR immunoreactivity. Research on diabetic mice kidneys and human podocytes exposed to diabetic glucose levels suggests that this inconsistency may result from disrupted intracellular (P)RR processing, likely due to increased Munc18-1 interacting protein 3. It follows that changes in FL-(P)RR cellular content mechanisms are specific to renal disease etiology, emphasizing the need for consideration in future studies exploring this receptor's involvement in renal damage of different origins

Novel role for thioredoxin reductase-2 in mitochondrial redox adaptations to obesogenic diet and exercise in heart and skeletal muscle

Increased fatty acid availability and oxidative stress are physiological consequences of exercise (Ex) and a high-fat, high-sugar (HFHS) diet. Despite these similarities, the global effects of Ex are beneficial, whereas HFHS diets are largely deleterious to the cardiovascular system. The reasons for this disparity are multifactorial and incompletely understood. We hypothesized that differences in redox adaptations following HFHS diet in comparison to exercise may underlie this disparity, particularly in mitochondria. Our objective in this study was to determine mechanisms by which heart and skeletal muscle (red gastrocnemius, RG) mitochondria experience differential redox adaptations to 12 weeks of HFHS diet and/or exercise training (Ex) in rats. Surprisingly, both HFHS feeding and Ex led to contrasting effects in heart and RG, in that mitochondrial H2O2 decreased in heart but increased in RG following both HFHS diet and Ex, in comparison to sedentary animals fed a control diet. These differences were determined to be due largely to increased antioxidant/anti-inflammatory enzymes in the heart following the HFHS diet, which did not occur in RG. Specifically, upregulation of mitochondrial thioredoxin reductase-2 occurred with both HFHS and Ex in the heart, but only with Ex in RG, and systematic evaluation of this enzyme revealed that it is critical for suppressing mitochondrial H2O2 during fatty acid oxidation. These findings are novel and important in that they illustrate the unique ability of the heart to adapt to oxidative stress imposed by HFHS diet, in part through upregulation of thioredoxin reductase-2. Furthermore, upregulation of thioredoxin reductase-2 plays a critical role in preserving the mitochondrial redox status in the heart and skeletal muscle with exercise.Funding from the National Institutes of Health, United State

VOLIP: A corpus of spoken Italian and a virtuous example of reuse of linguistic resources

The corpus VoLIP (The Voice of LIP) is an Italian speech resource which associates the audio signals to the orthographic transcriptions of the LIP Corpus. The LIP Corpus was designed to represent diaphasic, diatopic and diamesic variation. The Corpus was collected in the early '90s to compile a frequency lexicon of spoken Italian and its size was tailored to produce a reliable frequency lexicon for the first 3,000 lemmas. Therefore, it consists of about 500,000 word tokens for 60 hours of recording. The speech materials belong to five different text registers and they were collected in four different cities. Thanks to a modern technological approach VoLIP web service allows users to search the LIP corpus using IMDI metadata, lexical or morpho-syntactic entry keys, receiving as result the audio portions aligned to the corresponding required entry. The VoLIP corpus is freely available at the URL http://www.parlaritaliano.it

Evaluation of menstrual blood loss (MBL) by self-perception and pictorial methods and correlation to uterine myometrial pathology

Purpose: Evaluating menstrual blood loss (MBL) in primary healthcare is challenging. Our study aimed to assess MBL using two methods: self-perception and pictograms (Pictorial Blood Assessment Chart—PBAC and Menstrual Pictogram superabsorbent polymer-c version—MP) in women undergoing transvaginal ultrasound (TVS). Methods: We enrolled 221 premenopausal women with spontaneous menstruation, no hormonal therapy, and no ongoing pregnancy. They were divided into four age groups (12–20, 21–30, 31–40, and 41–55 years). Women self-reported normal (NMB) or heavy menstrual bleeding (HMB) and filled out PBAC and MP. A PBAC score ≥ 150 and MP score ≥ 80 ml indicated HMB. TVS was conducted on all patients, recording any pelvic pathologies. We compared self-perception with pictograms across the cohort, age groups, and ultrasound findings. Results: Of the cohort, 50.2% reported normal periods and 49.8% heavy periods. No significant differences were found between self-perception and pictograms in identifying NMB and HMB across all groups. However, significant differences were observed between PBAC and MP scores for NMB (56.1% vs 41.2%, p = 0.001) and HMB (43.9% vs 58.8%, p = 0.001), particularly in the 31–40 age group. Significant differences in PBAC and MP scores were noted between age groups 12–20 and 41–55, and 31–40 and 41–55. No significant differences were found between self-perception and pictograms regarding ultrasound findings like adenomyosis, fibroids, endometrial pathology, and uterine congenital malformations. Conclusion: Self-perception could be a reliable method for describing MBL across all age groups and ultrasound findings. Given the complexity and potential errors in using pictograms, clinicians should consider relying on self-perception for assessing menstrual cycle quantity