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This document is a correction notice for an article titled "Deoxycholic acid supplementation impairs glucose homeostasis in mice." The correction addresses several errors in the original article, including a misspelled author's name, an incorrect data availability statement, errors in figure legends, and errors in table legends. The correction provides the correct information for each of these errors. The article includes graphs and supporting tables that present data on the effects of deoxycholic acid supplementation on glucose homeostasis and fasting serum bile acid concentrations in mice. [Extracted from the article]

The sweet taste receptor, TAS1R2-TAS1R3, is expressed in taste bud cells, where it conveys sweetness, and also in intestinal enteroendocrine cells, where it may facilitate glucose absorption and assimilation. In the present study, our objective was to determine whether TAS1R2-TAS1R3 influences glucose metabolism bidirectionally via hyperactivation with 5 mM sucralose (n = 12) and inhibition with 2 mM sodium lactisole (n = 10) in mixture with 75 g glucose loads during oral glucose tolerance tests (OGTTs) in healthy humans. Plasma glucose, insulin, and glucagon were measured before, during, and after OGTTs up to 120 minutes post-prandially. We also assessed individual participants' sweet taste responses to sucralose and their sensitivities to lactisole sweetness inhibition. The addition of sucralose to glucose elevated plasma insulin responses to the OGTT (F(1, 11) = 4.55, p = 0.056). Sucralose sweetness ratings were correlated with early increases in plasma glucose (R2 = 0.41, p<0.05), as well as increases in plasma insulin (R2 = 0.38, p<0.05) when sucralose was added to the OGTT (15 minute AUC). Sensitivity to lactisole sweetness inhibition was correlated with decreased plasma glucose (R2 = 0.84, p<0.01) when lactisole was added to the OGTT over the whole test (120 minute AUC). In summary, stimulation and inhibition of the TAS1R2-TAS1R3 receptor demonstrates that TAS1R2-TAS1R3 helps regulate glucose metabolism in humans and may have translational implications for metabolic disease risk. [ABSTRACT FROM AUTHOR]

Mendelian randomization (MR) is an epidemiological framework using genetic variants as instrumental variables (IVs) to examine the causal effect of exposures on outcomes. Statistical methods based on unidirectional MR (UMR) are widely used to estimate the causal effects of exposures on outcomes in observational studies. To estimate the bidirectional causal effects between two phenotypes, investigators have naively applied UMR methods separately in each direction. However, bidirectional causal effects between two phenotypes create a feedback loop that biases the estimation when UMR methods are naively applied. To overcome this limitation, we proposed two novel approaches to estimate bidirectional causal effects using MR: BiRatio and BiLIML, which are extensions of the standard ratio, and limited information maximum likelihood (LIML) methods, respectively. We compared the performance of the two proposed methods with the naive application of UMR methods through extensive simulations of several scenarios involving varying numbers of strong and weak IVs. Our simulation results showed that when multiple strong IVs are used, the proposed methods provided accurate bidirectional causal effect estimation in terms of median absolute bias and relative median absolute bias. Furthermore, compared to the BiRatio method, the BiLIML method provided a more accurate estimation of causal effects when weak IVs were used. Therefore, based on our simulations, we concluded that the BiLIML should be used for bidirectional causal effect estimation. We applied the proposed methods to investigate the potential bidirectional relationship between obesity and diabetes using the data from the Multi-Ethnic Study of Atherosclerosis cohort. We used body mass index (BMI) and fasting glucose (FG) as measures of obesity and type 2 diabetes, respectively. Our results from the BiLIML method revealed the bidirectional causal relationship between BMI and FG in across all racial populations. Specifically, in the White/Caucasian population, a 1 kg/m2 increase in BMI increased FG by 0.70 mg/dL (95% confidence interval [CI]: 0.3517–1.0489; p = 8.43×10−5), and 1 mg/dL increase in FG increased BMI by 0.10 kg/m2 (95% CI: 0.0441–0.1640; p = 6.79×10−4). Our study provides novel findings and quantifies the effect sizes of the bidirectional causal relationship between BMI and FG. However, further studies are needed to understand the biological and functional mechanisms underlying the bidirectional pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: The supraclavicular fossa is the dominant location for human brown adipose tissue (BAT). Activation of BAT promotes non-shivering thermogenesis by utilization of glucose and free fatty acids and has been the focus of pharmacological and non-pharmacological approaches for modulation in order to improve body weight and glucose homeostasis. Sympathetic neural control of supraclavicular BAT has received much attention, but its innervation has not been extensively investigated in humans. METHODS: Dissection of the cervical region in human cadavers was performed to find the distribution of sympathetic nerve branches to supraclavicular fat pad. Furthermore, proximal segments of the 4th cervical nerve were evaluated histologically to assess its sympathetic components. RESULTS: Nerve branches terminating in supraclavicular fat pad were identified in all dissections, including those from the 3rd and 4th cervical nerves and from the cervical sympathetic plexus. Histology of the proximal segments of the 4th cervical nerves confirmed tyrosine hydroxylase positive thin nerve fibers in all fascicles with either a scattered or clustered distribution pattern. The scattered pattern was more predominant than the clustered pattern (80% vs. 20%) across cadavers. These sympathetic nerve fibers occupied only 2.48% of the nerve cross sectional area on average. CONCLUSIONS: Human sympathetic nerves use multiple pathways to innervate the supraclavicular fat pad. The present finding serves as a framework for future clinical approaches to activate human BAT in the supraclavicular region.

Accurate prediction of blood glucose levels is essential for type 1 diabetes optimizing insulin therapy and minimizing complications in patients with type 1 diabetes. Using ensemble learning algorithms is a promising approach. In this regard, this study proposes an improved stacking ensemble learning algorithm for predicting blood glucose level, in which three improved long short-term memory network models are used as the base model, and an improved nearest neighbor propagation clustering algorithm is adaptively weighted to this ensemble model. The OhioT1DM dataset is used to train and evaluate the performance of the proposed model. This study evaluated the performance of the proposed model using the Root Mean Square Error (RMSE), Mean Absolute Error (MAE), and Matthews Correlation Coefficient (MCC) as the evaluation metrics. The experimental results demonstrate that the proposed model achieves an RMSE of 1.425 mg/dL, MAE of 0.721 mg/dL, and MCC of 0.982 mg/dL for a 30-minute prediction horizon(PH), RMSE of 3.212 mg/dL, MAE of 1.605 mg/dL, and MCC of 0.950 mg/dL for a 45-minute PH; and RMSE of 6.346 mg/dL, MAE of 3.232 mg/dL, and MCC of 0.930 mg/dL for a 60-minute PH. Compared with the best non-ensemble model StackLSTM, the RMSE and MAE were improved by up to 27.92% and 65.32%, respectively. Clarke Error Grid Analysis and critical difference diagram revealed that the model errors were within 10%. The model proposed in this study exhibits state-of-the-art predictive performance, making it suitable for clinical decision-making and of significant importance for the effective treatment of diabetes in patients. [ABSTRACT FROM AUTHOR]

Hyperglycemia is commonly observed in critically ill patients and postcardiac arrest patients, with higher glucose levels and variability associated with poorer outcomes. In this study, we aim to compare glucose control in diabetic and nondiabetic patients using glycated hemoglobin (HbA1c) levels, providing insights for better glucose management strategies. This retrospective observational study was conducted at Seoul St. Mary's Hospital from February 2009 to May 2022. Blood glucose levels were measured hourly for 48 h after return of spontaneous circulation (ROSC), and a glucose management protocol was followed to maintain arterial blood glucose levels between 140 and 180 mg/dL using short-acting insulin infusion. Patients were categorized into four groups based on diabetes status and glycemic control. The primary outcomes assessed were neurological outcome and mortality at 6 months after cardiac arrest. Among the 332 included patients, 83 (25.0%) had a previous diabetes diagnosis, and 114 (34.3%) had an HbA1c of 6.0% or higher. At least one hyperglycemic episode was observed in 314 patients (94.6%) and hypoglycemia was found in 63 patients (19.0%) during 48 h. After the categorization, unrecognized diabetes was noticed in 51 patients with median HbA1c of 6.3% (interquartile range [IQR] 6.1–6.6). Patients with inadequate diabetes control had the highest initial HbA1c level (7.0%, IQR 6.5–7.8) and admission glucose (314 mg/dL, IQR 257–424). Median time to target glucose in controlled diabetes was significantly shorter with the slowest glucose reducing rate. The total insulin dose required to reach the target glucose level and cumulative insulin requirement during 48 h were different among the categories (p <0.001). Poor neurological outcomes and mortality were more frequently observed in patients with diagnosed diabetes. Occurrence of a hypoglycemic episode during the 48 h after ROSC was independently associated with poor neurologic outcomes (odds ratio [OR] 3.505; 95% confidence interval [CI], 2.382–9.663). Surviving patients following cardiac arrest exhibited variations in glucose hemodynamics and outcomes according to the categories based on their preexisting diabetes status and glycemic condition. Specifically, even experiencing a single episode of hypoglycemia during the acute phase could have an influence on unfavorable neurological outcomes. While the classification did not directly affect neurological outcomes, the present results indicate the need for a customized approach to glucose control based on these categories. [ABSTRACT FROM AUTHOR]

Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological treatment and dietary interventions are recommended to prevent the progression of pre-diabetes to T2DM. However, poor patient compliance leads to negligence of the dietary intervention and thus reduced drug efficiency. Momordica balsamina (MB) has been reported to possess anti-diabetic effects in type 1 diabetic rats. However, the effects of this medicinal plant in conjunction with dietary intervention on pre-diabetes have not yet been established. Consequently, this study sought to evaluate the effects of MB on glucose homeostasis in a diet-induced pre-diabetes rat model in the presence and absence of dietary intervention. Pre-diabetes was induced on male Sprague Dawley rats by a high fat high carbohydrate (HFHC) diet for a period of 20 weeks. Pre-diabetic male Sprague Dawley rats were treated with MB (250 mg/kg p.o.) in both the presence and absence of dietary intervention once a day every third day for a period of 12 weeks. The administration of MB with and without dietary intervention resulted in significantly improved glucose homeostasis through reduced caloric intake, body weights, with reduced plasma ghrelin concentration and glycated hemoglobin by comparison to the pre-diabetic control. MB administration also improved insulin sensitivity as evidenced by the expression of glucose transporter 4 (GLUT 4) and glycogen synthase on the prediabetic treated animals. These results suggest that MB has the potential to be used to manage pre-diabetes and prevent the progression to overt type 2 diabetes as it demonstrated the ability to restore glucose homeostasis even in the absence of dietary and lifestyle intervention. [ABSTRACT FROM AUTHOR]

The development of diabetes mellitus (DM) after living donor kidney transplantation (KT) is a risk factor for worsening transplant kidney function, cardiac disease, and cerebrovascular disease, which may affect prognosis after KT. At our institution, all patients' glucose tolerance is evaluated perioperatively by oral glucose tolerance tests (OGTTs) at pre-KT, and 3, 6, and 12 month (mo.) after KT. We analyzed the insulinogenic index (ISI) and homeostasis model assessment beta cell (HOMA-β) based on the immunoreactive insulin (IRI) levels to determine how glucose tolerance changed after KT in 214 patients who had not been diagnosed with DM before KT. In addition, we analyzed the body mass index (BMI) which may also influence glucose tolerance after KT. The concentration of tacrolimus (TAC) in blood was also measured as the area under the curve (AUC) to examine its effects at each sampling point. The preoperative-OGTTs showed that DM was newly diagnosed in 22 of 214 patients (10.3%) who had not been given a diagnosis of DM by the pre-KT fasting blood sugar (FBS) tests. The glucose tolerance was improved in 15 of 22 DM patients at 12 mo. after KT. ISI and IRI deteriorated only at 3 mo. after KT but improved over time. There was a trend of an inverse correlation between HOMA-β and TAC-AUC. We also found inverse correlations between IRI and an increase in BMI from 3 to 12 mo. after KT. Early corticosteroid withdrawal or the steroid minimization protocol with tacrolimus to maintain a low level of diabetogenic tacrolimus and BMI decrease after KT used by our hospital individualizes lifestyle interventions for each patient might contribute to an improvement in post-KT glucose tolerance. [ABSTRACT FROM AUTHOR]

Background: Undiagnosed diabetes in pregnancy is associated with stillbirth and perinatal complications, but standard testing for gestational diabetes using the oral glucose tolerance test (OGTT) is impractical and exacerbates healthcare inequalities. There is an urgent need to improve the accuracy, acceptability and accessibility of glucose testing in pregnancy. We qualitatively assessed the feasibility and acceptability of two alternative home-based methods of glucose testing in pregnant women, using continuous glucose monitoring (CGM), with or without a home-based OGTT. Methods: We recruited women with a singleton pregnancy at 28 weeks' gestation with ≥1 risk factor for gestational diabetes attending antenatal glucose testing. A Dexcom G6 CGM device was sited and women were asked to take a 75g OGTT solution (Rapilose) on day 4 after an overnight fast. Qualitative interviews were performed with 20 participants using video conferencing according to a semi-structured interview schedule and thematically analysed using NVIVO software. Results: 92 women were recruited; 73 also underwent a home OGTT. Women had an average of 6.9 days of glucose monitoring and found the CGM painless, easy to use with few or no adverse events. During the qualitative study, the main themes identified were reassurance and convenience. All women interviewed would recommend CGM and a home OGTT for diagnosis of gestational diabetes. Conclusions: CGM with or without a home OGTT is feasible and acceptable to pregnant women for diagnosis of gestational diabetes and offered advantages of convenience and reassurance. Further work is needed to clarify diagnostic thresholds for gestational diabetes using CGM metrics. [ABSTRACT FROM AUTHOR]

Aims: Glycemic variability has been suggested as a risk factor for diabetes complications but the precise deleterious mechanisms remain poorly understood. Since mitochondria are the main source of energy in heart and cardiovascular diseases remain the first cause of death in patients with diabetes, the aim of the study was to evaluate the impact of glucose swings on mitochondrial functions in the cardiomyocyte cell line HL-1. Methods: HL-1 cells were exposed to low (LG, 2.8 mmol/l), normal (NG, 5.5 mmol/l), high (HG, 25 mmol/l) or intermittent high glucose (IHG, swing between low and high) every 2h during 12h (short-time treatment) or every 12h during 72h (long-time treatment). Anaerobic catabolism of glucose was evaluated by measuring glucose consumption and lactate production, oxidative phosphorylation was evaluated by polarography and ATP measurement, mitochondrial superoxide anions and the mitochondrial membrane potential (MMP) were analysed using fluorescent probes, and the protein oxidation was measured by oxyblot. Results: IHG and HG increased glucose consumption and lactate production compared to LG and NG but without any difference between short- and long-time treatments. After 72h and unlike to LG, NG and HG, we didn't observe any increase of the mitochondrial respiration in the presence of succinate upon IHG treatment. IHG, and to a lesser extent HG, promoted a time-dependent decrease of the mitochondrial membrane potential compared to LG and NG treatments. HG and IHG also increased superoxide anion production compared to LG and NG both at 12 and 72h but with a higher increase for IHG at 72h. At last, both HG and IHG stimulated protein oxidation at 72h compared to LG and NG treatments. Conclusions: Our results demonstrated that exposure of HL-1 cells to glucose swings promoted time-dependent mitochondrial dysfunctions suggesting a deleterious effect of such condition in patients with diabetes that could contribute to diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Cognitive decline is one of the most widespread chronic complications of diabetes, which occurs in more than half of the patients with type 2 diabetes (T2DM). Emerging evidences have suggested that glucose variability (GV) is associated with the pathogenesis of diabetic complications. However, the influence of acute GV on cognitive dysfunction in T2DM is still controversial. The aim of the study was to evaluate the association between acute GV and cognitive defect in T2DM, and provide a most recent and comprehensive summary of the evidences in this research field. Methods: PubMed, Cochrane library, EMBASE, Web of science, Sinomed, China National Knowledge Infrastructure (CNKI), and Wanfang were searched for articles that reported on the association between acute GV and cognitive impairment in T2DM. Results: 9 eligible studies were included, with a total of 1263 patients with T2DM involved. Results showed that summary Fisher's z value was -0.23 [95%CI (-0.39, -0.06)], suggesting statistical significance (P = 0.006). Summary r value was -0.22 [95%CI (-0.37, -0.06)]. A lower cognitive performance was found in the subjects with greater glucose variation, which has statistical significance. Mean amplitude of glycemic excursions (MAGE) was associated with a higher risk of poor functional outcomes. Fisher's z value was -0.35 [95%CI (-0.43, -0.25)], indicating statistical significance (P = 0.011). Sensitivity analyses by omitting individual studies showed stability of the results. Conclusions: Overall, higher acute GV is associated with an increased risk of cognitive impairment in patients with T2DM. Further studies should be required to determine whether targeted intervention of reducing acute GV could prevent cognitive decline. [ABSTRACT FROM AUTHOR]

Exposure to traumatic stress leads to persistent, deleterious behavioral and biological changes in both human and non-human species. The effects of stress are not always consistent, however, as exposure to different stressors often leads to heterogeneous effects. The intensity of the stressor may be a key factor in determining the consequences of stress. While it is difficult to quantify intensity for many stress types, electric shock exposure provides us with a stressor that has quantifiable parameters (presentation length x intensity x number = shock volume). Therefore, to test the procedural differences in shock volume that may account for some reported heterogeneity, we used two common shock procedures. Learned helplessness is a commonly reported behavioral outcome, highlighted by a deficit in subsequent shuttle-box escape, which requires a relatively high-volume stress (HVS) of about 100 uncontrollable shocks. Conversely, stress-enhanced fear learning (SEFL) is another common behavioral outcome that requires a relatively moderate-volume stress (MVS) of only 15 shocks. We exposed rats to HVS, MVS, or no stress (NS) and examined the effects on subsequent fear learning and normal weight gain. We found doubly dissociable effects of the two levels of stress. MVS enhanced contextual fear learning but did not impact weight, while HVS produced the opposite pattern. In other words, more stress does not simply lead to greater impairment. We then tested the hypothesis that the different stress-induced sequalae arouse from an energetic challenge imposed on the hippocampus by HVS but not MVS. HVS rats that consumed a glucose solution did exhibit SEFL. Furthermore, rats exposed to MVS and glucoprivated during single-trial context conditioning did not exhibit SEFL. Consistent with the hypothesis that the inability of HVS to enhance fear learning is because of an impact on the hippocampus, HVS did enhance hippocampus-independent auditory fear learning. Finally, we provide evidence that stressors of different volumes produce dissociable changes in glutamate receptor proteins in the basolateral amygdala (BLA) and dorsal hippocampus (DH). The data indicate that while the intensity of stress is a critical determinant of stress-induced phenotypes that effect is nonlinear.

Objective: The degree of substitution (DS) of HES describes the average proportion of substituted glucose molecules in a starch molecule. Although no quantitative studies of the in vivo behavior of the DS have been conducted so far, most pharmacokinetic studies to date have measured HES concentrations using the enzymatic method. This method assumes that at any point in time after an infusion, the DS in a serum remains constant and is identical to the DS in the infused solution. In the present study, we examined the changes in the DS of HES 130/0.42 in vivo in an animal model and compared two methods of measuring HES concentrations in plasma (the enzymatic and the o-Toluidine method). Methodology: We randomized 22 pigs into 2 groups. After induction of anesthesia, the pigs received 500 ml or 1000 ml of HES 130/0.42 (Tetraspan®). The DS was measured directly after the infusion, then after 30, 60, 120 and 240 minutes. In determining the DS, the hydroxyethyl starch was extracted from the plasma and hydrolyzed with hydrochloric acid to form non-substituted glucose and hydroxyethyl glucose. Subsequently, the concentration of free unsubstituted glucose was determined enzymatically and the total concentration of all (i.e., substituted and unsubstituted) glucose molecules was determined using the o-Toluidine method. From this, the concentration of the substituted glucose (hydroxyethyl glucose) and the DS could be calculated. In addition, the HES concentration was measured first in vitro and then in vivo at any point after the infusion by both the enzymatic method and the o-Toluidine method. Results: The DS increased significantly directly after the infusion from 0.42 to 0.53 (for 500ml) or to 0.50 (for 1000ml); 4 hours later this had further increased to 0.55 and 0.54, respectively (p <0.0001). The HES concentration in vitro showed no significant difference (p = 0.17) when determined with the enzymatic and the o-Toluidine method. In contrast, the serum concentrations in vivo displayed significant differences (p<0.0001) between the two measurement methods. Immediately after the infusion of 500ml HES, the concentration measured with the o-Toluidine method was 31% higher than the one measured with the enzymatic method; 4 hours later, this discrepancy was still at 25%. For 1000 ml HES, the differences amounted to 16% and 25%, respectively. Conclusion: The DS of HES in vivo increases significantly over time. As a result, an HES concentration measured with the enzymatic method in vivo will be significantly lower than the same concentration determined with the o-Toluidine method. In future pharmacokinetic studies, HES concentrations should be measured using a method that takes into account changes in the DS in vivo. [ABSTRACT FROM AUTHOR]

Background: Lipids and glucose concentrations in the blood rise during pregnancy period. Poor control of these analytes results in cardio metabolic dysfunction. Despite this, there are no documented studies which investigate lipids and glucose among pregnant women in Tigrai, northern Ethiopia. Objective: The objective of this study was to assess lipid and glucose levels and identify their correlates among pregnant women in Tigrai, northern Ethiopia. Method: We conducted a facility-based cross sectional study comprising of systematically selected 200 pregnant women from July to October 2021. Those who were severely ill were excluded from the study. We used a structured questionnaire to collect socio-demographic and clinical characteristics of pregnant women. Lipids such as triglycerides, low density lipoprotein, cholesterol and blood glucose were also measured using Cobas C311 chemistry machine from plasma samples. The data were analyzed using SPSS version 25. Logistic regression was performed and statistical significance was declared at p-value < 0.05. Result: Proportion of pregnant women with cholesterol, triglyceride, low density lipoprotein and blood glucose levels above the upper limit of the normal range used for clinical decision were 26.5%, 43%, 44.5% and 21%, respectively. Pregnant women's income > = 10,000 ETB (AOR = 3.35; 95%CI: 1.46–7.66), age (AOR = 3.16; 95%CI: 1.03–9.68), gestational age 29–37 weeks (AOR = 8.02; 95%CI: 2.69–23.90) and having systolic blood pressure greater than 120 mmHg (AOR = 3.99; 95%CI: 1.64–9.75) demonstrated statistically significant association with raised levels of lipids. Conclusion and recommendation: Proportion of pregnant women with out of normal range values of lipids, particularly triglycerides and low density lipoprotein, is high. Gestational age is a strong predictor of increase in blood levels for both lipids. Provision of life style related health education and dietary intake to pregnant mothers matters. Moreover, monitoring lipid profile and glucose level during antenatal care period is essential. [ABSTRACT FROM AUTHOR]

The joint work of the stomach and the small intestine plays a fundamental role in human digestion. In the stomach, food is turned into a semi-fluid mixture that is slowly released into the small intestine, where most enzymatic reactions occur, and nutrients are absorbed as they become available. This whole process is closely related to glucose homeostasis, mainly because of the appearance of glucose in the portal system and the energetic expenditure of the process itself. The current phenomenological-based model describes such effects of the digestive process on blood glucose concentration. It considers enzymatic and mechanical transformations, energetic expenditure, and the impact of macro-nutrients, fiber, and water on overall digestion and glucose absorption. The model estimates the rate of glucose appearance in the portal vein and is intended to be further integrated into existing models for other human organs and used in model-based systems such as an artificial pancreas with automated insulin delivery. [ABSTRACT FROM AUTHOR]

Previous studies have shown that necrostatin-1 (Nec-1) supplementation improved the viability of murine islets following exposure to nitric oxide, increased the survival of human islets during hypoxic culture, and augmented the maturation of pre-weaned porcine islets (PPIs) after 7 days of tissue culture. A limitation of these studies is that only one concentration of Nec-1 was used, and no studies have determined the optimal dose of Nec-1 for PPIs. Thus, the present study examined the effects of Nec-1 on PPIs at four different doses-0, 25, 50, 100, and 200 μM-after 7 days of tissue culture when supplemented on day 3. PPIs were isolated from pancreata of pre-weaned Yorkshire piglets (8-15 days old) and cultured in a specific islet maturation media added with Nec-1 on day 3 of tissue culture at 4 different doses-0, 25, 50, 100, and 200 μM (n = 6 for each dose). After 7 days of tissue culture, islets were assessed for recovery, viability, endocrine cellular content, GLUT2 expression in beta cells, and insulin secretion after glucose challenge. Nec-1 did not affect the viability of both intact islets and dissociated islets cells during tissue culture regardless of doses. Islets cultured in media supplemented with Nec-1 at 100 μM, but not 25, 50, or 200 μM, had a significantly higher recovery, composition of endocrine cells, GLUT2 expression in beta cells, and insulin secretion capacity than control islets cultured in media without Nec-1 supplementation. Moreover, culturing islets in 200 μM Nec-1 supplemented media not only failed to improve the insulin release but resulted in a lower glucose-induced insulin stimulation index compared to islets cultured in media added with 100 μM Nec-1. Xenotransplantation using porcine islets continues to demonstrate scientific advances to justify this area of research. Our findings indicate that Nec-1 supplementation at 100 μM was most effective to enhance the in vitro maturation of PPIs during tissue culture.

Tubulointerstitial fibrosis is observed in diabetic nephropathy. It is still debated whether tubular cells, undergoing epithelial-mesenchymal transition (EMT) in high glucose (HG) conditions, may contribute to interstitial fibrosis development. In this study, we investigated the phenotypic and molecular EMT-like changes and the alteration of inflammatory and fibrogenic secretome induced by HG in human primary tubular cell cultures. Taking advantage of this in vitro cell model composed of proximal and distal tubular cells, we showed that HG-treated tubular cells acquired a fibroblast-like morphology with increased cytoplasmic stress fibers, maintaining the expression of the epithelial markers specific of proximal and distal tubular cells. HG increased Snail1, miRNA210 and Vimentin mesenchymal markers, decreased N-cadherin expression and migration ability of primary tubular cells, while E-cadherin expression and focal adhesion distribution were not affected. Furthermore, HG treatment of tubular cells altered the inflammatory cytokine secretion creating a secretome able to enhance the proliferation and migration of fibroblasts. Our findings show that HG promotes an activated state of partial EMT in human tubular primary cells and induces a pro-inflammatory and pro-fibrogenic microenvironment, supporting the active role of tubular cells in diabetic nephropathy onset. [ABSTRACT FROM AUTHOR]

Objectives: There has been a steady increase in the number of studies of the complex relationship between glucose and electrical cardiac activity which use simultaneous continuous glucose monitors (CGM) and continuous electrocardiogram (ECG). However, data collected on the same individual tend to be similar (yielding correlated or dependent data) and require analyses that take into account that correlation. Many opt for simplified techniques such as calculating one measure from the data collected and analyse one observation per subject. These simplified methods may yield inconsistent and biased results in some instances. In this systematic review, we aim to examine the adequacy of the statistical analyses performed in such studies and make recommendations for future studies. Research questions: What are the objectives of studies collecting simultaneous CGM and ECG data? Do methods used in analysing CGM and continuous ECG data fully optimise the data collected? Design: Systematic review. Data sources: PubMed and Web of Science. Methods: A comprehensive search of the PubMed and Web of Science databases to June 2022 was performed. Studies utilising CGM and continuous ECG simultaneously in people with diabetes were included. We extracted information about study objectives, technologies used to collect data and statistical analysis methods used for analysis. Reporting was done following PRISMA guidelines. Results: Out of 118 publications screened, a total of 31 studies met the inclusion criteria. There was a diverse array of study objectives, with only two studies exploring the same exposure-outcome relationship, allowing only qualitative analysis. Only seven studies (23%) incorporated methods which fully utilised the study data using methods that yield the correct power and minimize type I error rate. The rest (77%) used analyses that summarise the data first before analysis and/or totally ignored data dependency. Of those who applied more advanced methods, one study performed both simple and correct analyses and found that ignoring data structure resulted in no association whilst controlling for repeated measures yielded a significant relationship. Conclusion: Most studies underutilised statistical methods suitable for analysis of dynamic continuous data, potentially attenuating their statistical power and overall conclusions. We recommend that aggregated data be used only as exploratory analysis, while primary analysis should use methods applied to the raw data such as mixed models or functional data analyses. These methods are widely available in many free, open source software applications. [ABSTRACT FROM AUTHOR]

Introduction: Hyperglycemia is common in acute ischemic stroke and is associated with larger infarct volume and unfavorable functional outcome, also in patients who undergo reperfusion therapy. Hyperglycemia during reperfusion may be a therapeutic target. However, previous randomized trials on the effect of glucose lowering in the acute phase of ischemic stroke failed to demonstrate effects on clinical outcome. Inaccurate glucose measurements and not focussing on patients who undergo reperfusion therapy are possible explanations. Our aim was to study the feasibility and accuracy of continuous glucose monitoring (CGM) in patients with acute ischemic stroke undergoing endovascular treatment (EVT). Methods: All consecutive patients with ischemic stroke and large vessel occlusion (LVO) of the anterior circulation who were eligible for endovascular therapy within 24 hours of symptom onset and presenting at the emergency department of Isala Hospital Zwolle, the Netherlands, were enrolled in this study. CGM was performed using a Freestyle Libre Flash 2 device (FSL-CGM, Abbot Diabetes Care, Alameda, California, USA) which was implanted on arrival at the emergency department. Feasibility was defined as the number of patients who could be registered for 24 hours and delay in door-to-groin time because of sensor implantation. Accuracy of CGM versus capillary and venous based plasma glucose values was determined with the Parkes error grid analysis. Results: Twenty-three patients were included of whom 20 completed 24 hours monitoring (87%). One patient did not give permission to use the data; one sensor broke during implantation and one meter was broken after a sensor was shot in so no measurements could be recorded. There was no significant delay in treatment due to implantation of the sensor and no adverse events. One hundred percent of CGM data are in zones A and B of the Parkes error grid analysis so data out of the sensor can be interpreted as accurate. Conclusion: In this study, we showed that continuous glucose monitoring in patients with acute ischemic stroke due to large vessel occlusion of the anterior circulation in patients who were treated with endovascular therapy is feasible, safe and accurate. [ABSTRACT FROM AUTHOR]

The consumption of processed foods and sugary sodas in Western diets correlates with an increased incidence of obesity, metabolic syndromes such as type 2 diabetes, cardiovascular diseases, and autoimmune diseases including inflammatory bowel disease and rheumatoid arthritis. All these diseases have an inflammatory component, of which T lymphocytes can play a critical role in driving. Much has been learned regarding the importance of sugar, particularly glucose, in fueling effector versus regulatory T cells that can promote or dampen inflammation, respectively. In particular, glucose and its metabolic breakdown products via glycolysis are essential for effector T cell differentiation and function, while fatty acid-fueled oxidative phosphorylation supports homeostasis and function of regulatory T cells. Nevertheless, a critical knowledge gap, given the prevalence of diabetes in Western societies, is the impact of elevated glucose concentrations on the balance between effector versus regulatory T cells. To begin addressing this, we cultured naïve CD4+ T cells with different concentrations of glucose, and examined their differentiation into effector versus regulatory lineages. Surprisingly, high glucose promoted regulatory T cell differentiation and inhibited Th1 effector differentiation. This skewing towards the regulatory lineage occurred via an indirect mechanism that depends on lactate produced by activated glycolytic T cells. Addition of lactate to the T cell differentiation process promotes the differentiation of Treg cells, and activates Akt/mTOR signaling cascade. Hence, our findings suggest the existence of a novel feedback mechanism in which lactate produced by activated, differentiating T cells skews their lineage commitment towards the regulatory fate. [ABSTRACT FROM AUTHOR]

Over the last two decades, the incidence of gestational diabetes (GDM) has almost doubled resulting in almost 9% of pregnant women diagnosed with GDM. Occurring more frequently than GDM is impaired glucose tolerance (IGT), also known as pre-diabetes, but it has been understudied during pregnancy resulting in a lack of clinical recommendations of maternal and fetal surveillance. The purpose of this retrospective, cross-sectional study was to examine the association between microbial diversity and function of the maternal microbiome with IGT while adjusting for confounding variables. We hypothesized that reduced maternal microbial diversity and increased gene abundance for insulin resistance function will be associated with IGT as defined by a value greater than 140 mg/dL on the glucose challenge test. In the examination of microbial composition between women with IGT and those with normal glucose tolerance (NGT), we found five taxa which were significantly different. Taxa higher in participants with impaired glucose tolerance were Ruminococcacea (p = 0.01), Schaalia turicensis (p<0.05), Oscillibacter (p = 0.03), Oscillospiraceae (p = 0.02), and Methanobrevibacter smithii (p = 0.04). When we further compare participants who have IGT by their pre-gravid BMI, five taxa are significantly different between the BMI groups, Enterobacteriaceae, Dialister micraerophilus, Campylobacter ureolyticus, Proteobacteria, Streptococcus Unclassified (species). All four metrics including the Shannon (p<0.00), Simpson (p<0.00), Inverse Simpson (p = 0.04), and Chao1 (p = 0.04), showed a significant difference in alpha diversity with increased values in the impaired glucose tolerance group. Our study highlights the important gastrointestinal microbiome changes in women with IGT during pregnancy. Understanding the role of the microbiome in regulating glucose tolerance during pregnancy helps clinicians and researchers to understand the importance of IGT as a marker for adverse maternal and neonatal outcomes. [ABSTRACT FROM AUTHOR]

Hypothesis: Glycaemic variability (GV) refers to fluctuations in the blood glucose level and may contribute to complications in patients suffering from Diabetes. Several studies show negative effects of GV on the cardiovascular system, however there is still a lack of conclusive evidence. Using an explorative cardiovascular panel, it is possible to simultaneously measure the effects on proteins relevant for cardiovascular processes. The aim of this study was to investigate the effects of rapid glucose excursions on cardiovascular and metabolic parameters in healthy individuals. Methods: An explorative single-blinded cross-over study was performed in ten healthy men. Subjects received 3 times 20 grams of glucose i.v. over 5 minutes or 60 grams of glucose continuously over 3 hours. Blood was taken for repeated measurements of the cardiovascular panel over the following 6 hours and again after 24 and 48 hours. Results: We observed a significant elevation of 7 cardiovascular biomarkers (BMP6, SLAMF7, LOX-1, ADAMTS13, IL-1RA, IL-4RA, PTX3) at t = 360min after rapid glucose infusion compared to a continuous glucose infusion. Conclusions: Intraday GV seems to have acute effects on cardiovascular proteins in healthy test persons. Rapid glucose administration compared to continuous administration showed significant changes in BMP6, SLAMF7, ADAMTS13, IL1RA, PTX3, IL-4RA and LOX-1. Clinical trial registration: NCT04488848. [ABSTRACT FROM AUTHOR]

In the post genomic era, high throughput data augment stoichiometric flux balance models to compute accurate metabolic flux states, growth and energy phenotypes. Investigating altered metabolism in the context of evolved resistant genotypes potentially provide simple strategies to overcome drug resistance and induce susceptibility to existing antibiotics. A genome-scale metabolic model (GSMM) for Chromobacterium violaceum, an opportunistic human pathogen, was reconstructed using legacy data. Experimental constraints were used to represent antibiotic susceptible and resistant populations. Model predictions were validated using growth and respiration data successfully. Differential flux distribution and metabolic reprogramming were identified as a response to antibiotics, chloramphenicol and streptomycin. Streptomycin resistant populations (StrpR) redirected tricarboxylic acid (TCA) cycle flux through the glyoxylate shunt. Chloramphenicol resistant populations (ChlR) resorted to overflow metabolism producing acetate and formate. This switch to fermentative metabolism is potentially through excess reducing equivalents and increased NADH/NAD ratios. Reduced proton gradients and changed Proton Motive Force (PMF) induced by antibiotics were also predicted and verified experimentally using flow cytometry based membrane potential measurements. Pareto analysis of NADH and ATP maintenance showed the decoupling of electron transfer and ATP synthesis in StrpR. Redox homeostasis and NAD+ cycling through rewiring metabolic flux was implicated in re-sensitizing antibiotic resistant C. violaceum. These approaches can be used to probe metabolic vulnerabilities of resistant pathogens. On the verge of a post-antibiotic era, we foresee a critical need for systems level understanding of pathogens and host interaction to extend shelf life of antibiotics and strategize novel therapies.

INTRODUCTION: Urocortin 2 (Ucn2) is a 38-amino acid peptide of the corticotropin-releasing factor family. Intravenous (IV) delivery of an adeno-associated virus vector serotype 8 encoding Ucn2 (AAV8.Ucn2) increases insulin sensitivity and glucose disposal in mice with insulin resistance. OBJECTIVE: To determine the effects of Ucn2 on liver metabolome. METHODS: Six-week-old C57BL6 mice were divided into normal chow (CHOW)-fed and high fat diet (HFD)-fed groups. The animals received saline, AAV8 encoding no gene (AAV8.Empt) or AAV8.Ucn2 (2x1013 genome copy/kg, IV injection). Livers were isolated from CHOW-fed and HFD-fed mice and analyzed by untargeted metabolomics. Group differences were statistically analyzed. RESULTS: In CHOW-fed mice, AAV8.Ucn2 gene transfer (vs. saline) altered the metabolites in glycolysis, pentose phosphate, glycogen synthesis, glycogenolysis, and choline-folate-methionine signaling pathways. In addition, AAV8.Ucn2 gene transfer increased amino acids and peptides, which were associated with reduced protein synthesis. In insulin resistant (HFD-induced) mice, HFD (vs CHOW) altered 448 (112 increased and 336 decreased) metabolites and AAV8.Ucn2 altered 239 metabolites (124 increased and 115 reduced) in multiple pathways. There are 61 metabolites in 5 super pathways showed interactions between diet and AAV8.Ucn2 treatment. Among them, AAV8.Ucn2 gene transfer reversed HFD effects on 13 metabolites. Finally, plasma Ucn2 effects were determined using a 3-group comparison of HFD-fed mice that received AAV8.Ucn2, AAV.Empt or saline, where 18 metabolites that altered by HFD (15 increased and 3 decreased), but restored levels to that seen in CHOW-fed mice by increased plasma Ucn2. CONCLUSIONS: Metabolomics study revealed that AAV8.Ucn2 gene transfer, through increased plasma Ucn2, provided counter-HFD effects in restoring hepatic metabolites to normal levels, which could be the underlying mechanisms for Ucn2 effects on increasing glucose disposal and reducing insulin assistance.

IntroductionUrocortin 2 (Ucn2) is a 38-amino acid peptide of the corticotropin-releasing factor family. Intravenous (IV) delivery of an adeno-associated virus vector serotype 8 encoding Ucn2 (AAV8.Ucn2) increases insulin sensitivity and glucose disposal in mice with insulin resistance.ObjectiveTo determine the effects of Ucn2 on liver metabolome.MethodsSix-week-old C57BL6 mice were divided into normal chow (CHOW)-fed and high fat diet (HFD)-fed groups. The animals received saline, AAV8 encoding no gene (AAV8.Empt) or AAV8.Ucn2 (2x1013 genome copy/kg, IV injection). Livers were isolated from CHOW-fed and HFD-fed mice and analyzed by untargeted metabolomics. Group differences were statistically analyzed.ResultsIn CHOW-fed mice, AAV8.Ucn2 gene transfer (vs. saline) altered the metabolites in glycolysis, pentose phosphate, glycogen synthesis, glycogenolysis, and choline-folate-methionine signaling pathways. In addition, AAV8.Ucn2 gene transfer increased amino acids and peptides, which were associated with reduced protein synthesis. In insulin resistant (HFD-induced) mice, HFD (vs CHOW) altered 448 (112 increased and 336 decreased) metabolites and AAV8.Ucn2 altered 239 metabolites (124 increased and 115 reduced) in multiple pathways. There are 61 metabolites in 5 super pathways showed interactions between diet and AAV8.Ucn2 treatment. Among them, AAV8.Ucn2 gene transfer reversed HFD effects on 13 metabolites. Finally, plasma Ucn2 effects were determined using a 3-group comparison of HFD-fed mice that received AAV8.Ucn2, AAV.Empt or saline, where 18 metabolites that altered by HFD (15 increased and 3 decreased), but restored levels to that seen in CHOW-fed mice by increased plasma Ucn2.ConclusionsMetabolomics study revealed that AAV8.Ucn2 gene transfer, through increased plasma Ucn2, provided counter-HFD effects in restoring hepatic metabolites to normal levels, which could be the underlying mechanisms for Ucn2 effects on increasing glucose disposal and reducing insulin assistance.

Tamoxifen is a mixed agonist/antagonist estrogen analogue that is frequently used to induce conditional gene deletion in mice using Cre-loxP mediated gene recombination. Tamoxifen is routinely employed in extremely high-doses relative to typical human doses to induce efficient gene deletion in mice. Although tamoxifen has been widely assumed to have no influence upon β-cells, the acute developmental and functional consequences of high-dose tamoxifen upon glucose homeostasis and adult β-cells are largely unknown. We tested if tamoxifen influences glucose homeostasis in male mice of various genetic backgrounds. We then carried out detailed histomorphometry studies of mouse pancreata. We also performed gene expression studies with islets of tamoxifen-treated mice and controls. Tamoxifen had modest effects upon glucose homeostasis of mixed genetic background (F1 B6129SF1/J) mice, with fasting hyperglycemia and improved glucose tolerance but without overt effects on fed glucose levels or insulin sensitivity. Tamoxifen inhibited proliferation of β-cells in a dose-dependent manner, with dramatic reductions in β-cell turnover at the highest dose (decreased by 66%). In sharp contrast, tamoxifen did not reduce proliferation of pancreatic acinar cells. β-cell proliferation was unchanged by tamoxifen in 129S2 mice but was reduced in C57Bl6 genetic background mice (decreased by 59%). Gene expression studies revealed suppression of RNA for cyclins D1 and D2 within islets of tamoxifen-treated mice. Tamoxifen has a cytostatic effect on β-cells, independent of changes in glucose homeostasis, in mixed genetic background and also in C57Bl6 mice. Tamoxifen should be used judiciously to inducibly inactivate genes in studies of glucose homeostasis.

BackgroundDiabetic cardiomyopathy (DM CMP) is defined as cardiomyocyte damage and ventricular dysfunction directly associated with diabetes independent of concomitant coronary artery disease or hypertension. Matrix metalloproteinases (MMPs), especially MMP-2, have been reported to underlie the pathogenesis of DM CMP by increasing extracellular collagen content.PurposeWe hypothesized that two discrete MMP-2 isoforms (full length MMP-2, FL-MMP-2; N-terminal truncated MMP-2, NTT-MMP-2) are induced by high glucose stimulation in vitro and in an experimental diabetic heart model.MethodsRat cardiomyoblasts (H9C2 cells) were examined to determine whether high glucose can induce the expression of the two isoforms of MMP-2. For the in vivo study, we used the streptozotocin-induced DM mouse heart model and age-matched controls. The changes of each MMP-2 isoform expression in the diabetic mice hearts were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical stains were conducted to identify the location and patterns of MMP-2 isoform expression. Echocardiography was performed to compare and analyze the changes in cardiac function induced by diabetes.ResultsQuantitative RT-PCR and immunofluorescence staining showed that the two MMP-2 isoforms were strongly induced by high glucose stimulation in H9C2 cells. Although no definite histologic features of diabetic cardiomyopathy were observed in diabetic mice hearts, left ventricular systolic dysfunction was determined by echocardiography. Quantitative RT-PCR and IHC staining showed this abnormal cardiac function was accompanied with the increases in the mRNA levels of the two isoforms of MMP-2 and related to intracellular localization.ConclusionTwo isoforms of MMP-2 were induced by high glucose stimulation in vitro and in a Type 1 DM mouse heart model. Further study is required to examine the role of these isoforms in DM CMP.

Systemic glucose levels can be modulated with specific solar wavelengths that influence mitochondrial metabolism. Mitochondrial respiration can be modulated using light that shifts ATP production with exceptional conservation of effect across species, from insects to humans. Known wavelengths have opposing effects of photobiomodulation, with longer wavelengths (660–900 nm red/infrared) increasing ATP production, and 420 nm (blue) light suppressing metabolism. Increasing mitochondrial respiration should result in a greater demand for glucose, and a decrease should result in a reduced demand for glucose. Here we have tested the hypothesis that these wavelengths alter circulating glucose concentration. We first established an oral glucose tolerance test curve in a bumblebee model, which showed sustained increase in systemic glucose beyond that seen in mammals, with a gradual normalisation over eight hours. This extended period of increased systemic glucose provided a stable model for glucose manipulation. Bees were starved overnight and given a glucose load in the morning. In the first group glucose levels were examined at hourly intervals. In the second group, bees were additionally exposed to either 670 nm or 420 nm light and their blood glucose examined. Increasing mitochondrial activity with 670 nm light at the peak of circulating glucose, resulted in a significant 50% reduction in concentration measured. Exposure to 420nm light that retards mitochondrial respiration elevated systemic glucose levels by over 50%. The impact of 670 nm and 420 nm on mitochondria is highly conserved. Hence, different wavelengths of visible light may be used to modulate systemic metabolism bidirectionally and may prove an effective agent in mammals. [ABSTRACT FROM AUTHOR]

Background: Androgen receptor (AR) is a potential therapeutic target in triple-negative breast cancer (TNBC). We aimed to elucidate the association of AR expression with glucose metabolic features in TNBC. Methods: Two independent datasets were analyzed: FDG PET data of our institution and a public dataset of GSE135565. In PET analysis, patients with TNBC who underwent pretreatment PET between Jan 2013 and Dec 2017 were retrospectively enrolled. Clinicopathologic features and maximum standardized uptake value (SUVmax) of tumors were compared with AR expression. In GSE135565 dataset, glycolysis score was calculated by the pattern of glycolysis-related genes, and of which association with SUVmax and AR gene expression were analyzed. Results: A total of 608 female patients were included in the PET data of our institution. SUVmax was lower in AR-positive tumors (P < 0.001) and correlated with lower AR expression (rho = –0.26, P < 0.001). In multivariate analysis, AR was a deterministic factor for low SUVmax (P = 0.012), along with other key clinicopathologic features. In the GSE135565 dataset, AR expression also exhibited a negative correlation with SUVmax (r = –0.34, P = 0.001) and the glycolysis score (r = –0.27, P = 0.013). Conclusions: Low glucose metabolism is a signature of AR expression in TNBC. It is suggested that evaluation of AR expression status needs to be considered in clinical practice particularly in TNBC with low glucose metabolism. [ABSTRACT FROM AUTHOR]

Bile acids are critical contributors to the regulation of whole body glucose homeostasis; however, the mechanisms remain incompletely defined. While the hydrophilic bile acid subtype, ursodeoxycholic acid, has been shown to attenuate hepatic endoplasmic reticulum (ER) stress and thereby improve glucose regulation in mice, the effect of hydrophobic bile acid subtypes on ER stress and glucose regulation in vivo is unknown. Therefore, we investigated the effect of the hydrophobic bile acid subtype, deoxycholic acid (DCA), on ER stress and glucose regulation. Eight week old C57BL/6J mice were fed a high fat diet supplemented with or without DCA. Glucose regulation was assessed by oral glucose tolerance and insulin tolerance testing. In addition, circulating bile acid profile and hepatic insulin and ER stress signaling were measured. DCA supplementation did not alter body weight or food intake, but did impair glucose regulation. Consistent with the impairment in glucose regulation, DCA increased the hydrophobicity of the circulating bile acid profile, decreased hepatic insulin signaling and increased hepatic ER stress signaling. Together, these data suggest that dietary supplementation of DCA impairs whole body glucose regulation by disrupting hepatic ER homeostasis in mice.

The fluorescent derivative of glucose, 2-Deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)-amino]-D-glucose (2NBDG), is a widely used surrogate reagent to visualize glucose uptake in live cells at single cell resolution. Using CRISPR-Cas9 gene editing in 5TGM1 myeloma cells, we demonstrate that ablation of the glucose transporter gene Slc2a1 abrogates radioactive glucose uptake but has no effect on the magnitude or kinetics of 2NBDG import. Extracellular 2NBDG, but not NBD-fructose was transported by primary plasma cells into the cytoplasm suggesting a specific mechanism that is unlinked from glucose import and that of chemically similar compounds. Neither excess glucose nor pharmacological inhibition of GLUT1 impacted 2NBDG uptake in myeloma cells or primary splenocytes. Genetic ablation of other expressed hexose transporters individually or in combination with one another also had no impact on 2NBDG uptake. Ablation of the genes in the Slc29 and Slc35 families of nucleoside and nucleoside sugar transporters also failed to impact 2NBDG import. Thus, cellular uptake of 2NBDG is not necessarily a faithful indicator of glucose transport and is promoted by an unknown mechanism. [ABSTRACT FROM AUTHOR]

Background and objectives: To understand the utility of glycated haemoglobin (HBA1C) in screening for diabetes and Abnormal Glucose Regulation (AGR) in primary care, we compared its performance to that of the fasting plasma glucose (FPG) test. Methods: This was a prospective diagnostic accuracy study conducted in eastern Uganda. Patients eligible for inclusion were consecutive adults, 30–75 years, receiving care at the outpatient department of a general hospital in eastern Uganda. We determined the sensitivity, specificity and optimum cut-off points for HBA1C and FPG tests using the oral glucose tolerance test (OGTT) as a clinical reference standard. Results: A total of 1659 participants underwent FPG testing of whom 310 were also HBA1C and OGTT tested. A total of 113 tested positive for diabetes and 168 for AGR on the OGTT. At recommended cut-off points for diabetes, the HBA1C and FPG tests had comparable sensitivity [69.8% (95% CI 46.3–86.1) versus 62.6% (95% CI 41.5–79.8), respectively] and specificity [98.6% (95% CI 95.4–99.6) versus 99.4% (95% CI 98.9–99.7), respectively]. Similarly, the sensitivity of HBA1C and the FPG tests for Abnormal Glucose Regulation (AGR) at ADA cut-offs were comparable [58.9% (95% CI 46.7–70.2) vs 47.7% (95% CI 37.3–58.4), respectively]; however, the HBA1C test had lower specificity [70.7% (95% CI 65.1–75.8)] than the FPG test [93.5% (95% CI 88.6–96.4)]. At the optimum cut-offs points for diabetes [45.0 mmol/mol (6.3%) for HBA1C and 6.4 mmol/L (115.2 mg/dl) for FPG], HBA1C and FPG sensitivity [71.2% (95% CI 46.9–87.8) versus 72.7% (95% CI 49.5–87.8), respectively] and specificity [95.1% (95% CI91.8 97.2) versus 98.7% (95% CI 98.0 99.2), respectively] were comparable. Similarly, at the optimum cut-off points for AGR [42.0 mmol/mol (6.0%) for the HBA1C and 5.5 mmol/l (99.0 mg/dl) for the FPG test], HBA1C and FPG sensitivity [42.3% (95% CI 31.8–53.6) and 53.2 (95% CI 43.1–63.1), respectively] and specificity [89.1% (95% CI 84.1 92.7) and 92.7% (95% CI 91.0 94.1), respectively] were comparable. Discussion: HBA1C is a viable alternative diabetes screening and confirmatory test to the FPG test; however, the utility of both tests in screening for prediabetes in this outpatient population is limited. [ABSTRACT FROM AUTHOR]

Background: Breast cancer chemotherapy with high dose alkylating agents is severely limited by their collateral toxicity to crucial normal tissues such as immune and gut cells. Taking advantage of the selective dependence of cancer cells on high glucose and combining glucose deprivation with these agents could produce therapeutic synergy. Methods: In this study we examined the effect of glucose as well as its deprivation, and antagonism using the non-metabolized analogue 2-deoxy glucose, on the proliferation of several breast cancer cell lines MCF7, MDA-MB-231, YS1.2 and pII and one normal breast cell line, using the MTT assay. Motility was quantitatively assessed using the wound healing assay. Lactate, as the end product of anaerobic glucose metabolism, secreted into culture medium was measured by a biochemical assay. The effect of paclitaxel and doxorubicin on cell proliferation was tested in the absence and presence of low concentrations of glucose using MTT assay. Results: In all cell lines, glucose supplementation enhanced while glucose deprivation reduced both their proliferation and motility. Lactate added to the medium could substitute for glucose. The inhibitory effects of paclitaxel and doxorubicin were significantly enhanced when glucose concentration was decreased in the culture medium, requiring 1000-fold lesser concentration to achieve a similar degree of inhibition to that seen in glucose-containing medium. Conclusion: Our data show that a synergy was obtained by combining paclitaxel and doxorubicin with glucose reduction to inhibit cancer cell growth, which in vivo, might be achieved by applying a carbohydrate-restricted diet during the limited phase of application of chemotherapy; this could permit a dose reduction of the cytotoxic agents, resulting in greater tolerance and lesser side effects. [ABSTRACT FROM AUTHOR]

Glucose tolerance tests (GTT) are commonly performed in beef cattle to evaluate the glucose-insulin signaling pathway. Blood samples are obtained via a catheter and then transferred back to the laboratory for further analysis. A hand-held glucometer used chute-side can make performing GTT's and quantifying blood glucose concentration much easier and faster for research purposes. The purpose of this study was to evaluate the agreement between a hand-held electronic glucometer (Precision Xtra; Abbott Diabetes Care Inc., Mississauga, ON, Canada) for chute-side use in beef cattle compared with a colorimetric assay in the laboratory (Stanbio Glucose LiquiColor; Stanbio Laboratory, Boerne, TX, USA). A GTT was performed on 13 Simmental × Angus steers during the growing phase. Blood samples were obtained via a jugular catheter. Glucometer readings were taken immediately after blood was sampled from the jugular with no preservative, and laboratory measurements were conducted on plasma preserved with sodium fluoride. A paired t-test (P = 0.40), Pearson's correlation (P < 0.001; r = 0.95), Bland-Altman plot, and Lin's concordance correlation coefficient (LCCC = 0.90) were completed to evaluate the performance of the glucometer relative to the results from the laboratory assay. Based on the results, we conclude that the glucometer is an acceptable method for measuring blood glucose concentration in beef cattle under field conditions. [ABSTRACT FROM AUTHOR]

Background: Prolonged sitting is associated with cardiometabolic and vascular disease. Despite emerging evidence regarding the acute health benefits of interrupting prolonged sitting time, the effectiveness of different modalities in older adults (who sit the most) is unclear.Methods: In preparation for a future randomized controlled trial, we enrolled 10 sedentary, overweight or obese, postmenopausal women (mean age 66 years ±9; mean body mass index 30.6 kg/m2 ±4.2) in a 4-condition, 4-period crossover feasibility pilot study in San Diego to test 3 different sitting interruption modalities designed to improve glucoregulatory and vascular outcomes compared to a prolonged sitting control condition. The interruption modalities included: a) 2 minutes standing every 20 minutes; b) 2 minutes walking every hour; and c) 10 minutes standing every hour. During each 5-hr condition, participants consumed two identical, standardized meals. Blood samples, blood pressure, and heart rate were collected every 30 minutes. Endothelial function of the superficial femoral artery was measured at baseline and end of each 5-hr condition using flow-mediated dilation (FMD). Participants completed each condition on separate days, in randomized order. This feasibility pilot study was not powered to detect statistically significant differences in the various outcomes, however, analytic methods (mixed models) were used to test statistical significance within the small sample size.Results: Nine participants completed all 4 study visits, one participant completed 3 study visits and then was lost to follow up. Net incremental area under the curve (iAUC) values for postprandial plasma glucose and insulin during the 5-hr sitting interruption conditions were not significantly different compared to the control condition. Exploratory analyses revealed that the 2-minute standing every 20 minutes and the 2-minute walking every hour conditions were associated with a significantly lower glycemic response to the second meal compared to the first meal (i.e., condition-matched 2-hour post-lunch glucose iAUC was lower than 2-hour post-breakfast glucose iAUC) that withstood Bonferroni correction (p = 0.0024 and p = 0.0084, respectively). Using allometrically scaled data, the 10-minute standing every hour condition resulted in an improved FMD response, which was significantly greater than the control condition after Bonferroni correction (p = 0.0033).Conclusion: This study suggests that brief interruptions in prolonged sitting time have modality-specific glucoregulatory and vascular benefits and are feasible in an older adult population. Larger laboratory and real-world intervention studies of pragmatic and effective methods to change sitting habits are needed.ClinicalTrials.gov NCT02743286.

Millimetre-wave frequencies are promising for sensitive detection of glucose levels in the blood, where the temperature effect is insignificant. All these features provide the feasibility of continuous, portable, and accurate monitoring of glucose levels. This paper presents a metamaterial-inspired resonator comprising five split-rings to detect glucose levels at 24.9 GHz. The plexiglass case containing blood is modelled on the sensor's surface and the structure is simulated for the glucose levels in blood from 50 mg/dl to 120 mg/dl. The novelty of the sensor is demonstrated by the capability to sense the normal glucose levels at millimetre-wave frequencies. The dielectric characteristics of the blood are modelled by using the Debye parameters. The proposed design can detect small changes in the dielectric properties of blood caused by varying glucose levels. The variation in the transmission coefficient for each glucose level tested in this study is determined by the quality factor and resonant frequency. The sensor presented can detect the change in the quality factor of transmission response up to 2.71/mg/dl. The sensor's performance has also been tested to detect diabetic hyperosmolar syndrome. The sensor showed a linear shift in resonant frequency with the change in glucose levels, and an R2 of 0.9976 was obtained by applying regression analysis. Thus, the sensor can be used to monitor glucose in a normal range as well as at extreme levels. [ABSTRACT FROM AUTHOR]

Impaired glucose tolerance is a major risk factor for type 2 diabetes (T2D) and several cardiometabolic disorders. To identify genetic loci underlying fasting glucose levels, we conducted an analysis of 9,232 individuals of European ancestry who at enrollment were either nondiabetic or had untreated type 2 diabetes. Multivariable linear mixed models were used to test for associations between fasting glucose and 7.9 million SNPs, with adjustment for age, body mass index (BMI), sex, significant principal components of the genotypes, and cryptic relatedness. Three previously discovered loci were genome-wide significant, with the lead SNPs being rs1260326, a missense variant in GCKR (p = 1.06×10−8); rs560887, an intronic variant in G6PC2 (p = 3.39×10−11); and rs13266634, a missense variant in SLC30A8 (p = 4.28×10−10). Fine mapping, genome-wide conditional analysis, and functional annotation indicated that the three loci were independently associated with fasting glucose. Each copy of an alternate allele at any of these three SNPs was associated with a reduction of 0.012 mmol/L in fasting glucose levels (p = 8.0×10−28), and this association was replicated in trans-ethnic analysis of 14,303 individuals (p = 2.2×10−16). The three SNPs were jointly associated with significantly reduced T2D risk, with an odds ratio (95% CI) of 0.93 (0.88, 0.98) per protective allele. Our findings implicate additive effects across pathophysiological pathways involved in type 2 diabetes, including glycolysis, gluconeogenesis, and insulin secretion. Since none of the individuals homozygous for the alternate alleles at all three loci has T2D, it might be possible to use a genetic predictor of fasting glucose levels to identify individuals at low vs. high risk of developing type 2 diabetes. [ABSTRACT FROM AUTHOR]

Maternal malnutrition plays a crucial role in functional development, resulting in behavioral, cognitive, and metabolic abnormalities and disturbances. "Cafeteria diet" has been linked to obesity, metabolic syndrome, diabetes, and other metabolic disruptions in the mammalian lifespan. However, there are very few reports about the effect of intrauterine and early postnatal malnutrition on the circadian rhythm programming of energy metabolites. In mammals, circadian rhythm central control is fundamental for correct interaction with the environment and physiological regulation. Exposure to malnutrition during development imprints metabolic programming throughout life on the central nervous system and peripheral systems. Lifespan studies exploring the effect of high fat/low protein diet administered during critical periods of development are scarce. The present study explored the effect of intrauterine and perinatal malnutrition induced by a high fat/low protein diet (Cafeteria Diet) on circadian and peripheral oscillators controlling glucose, insulin, and triglycerides in rats at 40 and 90 days of age. We evaluated plasma glucose and triglyceride levels in 6 Zeitgeber times, in addition to an intraperitoneal glucose tolerance test (IpTGT) and homeostasis model assessment of insulin resistance (HOMA-IR) at two time-points over 24h. Our results show that offspring of malnourished dams fed cafeteria diet present alterations in circadian rhythmicity of glucose and triglycerides associated with a change in glucose tolerance and insulin sensibility differentially regulated at the development stage and time of day. Intrauterine and early malnutrition due to a cafeteria diet produces maladaptive responses and programs energetic metabolism at several developmental stages during the lifespan., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bustamante-Valdez et al. This 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.)

Background: Despite conflicting findings in the current literature regarding the correlation between contraceptives and maternal health consequences, statistical analyses indicate that family planning may decrease the occurrence of such outcomes. Consequently, it is crucial to assess the capability of family planning to mitigate adverse maternal health outcomes., Objectives: This review investigates the effects of modern contraceptive use on maternal health., Search Methods: This systematic review is registered on Prospero (CRD42022332783). We searched numerous databases with an upper date limit of February 2022 and no geographical boundaries., Selection Criteria: We included observational studies, including cross-sectional, cohort, case-control studies, and non-RCT with a comparison group. We excluded systematic reviews, scoping reviews, narrative reviews, and meta-analyses from the body of this review., Main Results: The review included nineteen studies, with five studies reporting a reduction in maternal mortality linked to increased access to family planning resources and contraceptive use. Another three studies examined the impact of contraception on the risk of preeclampsia and our analysis found that preeclampsia risk was lower by approximately 6% among contraceptive users (95% CI 0.82-1.13) compared to non-users. Two studies assessed the effect of hormonal contraceptives on postpartum glucose tolerance and found that low-androgen contraception was associated with a reduced risk of gestational diabetes (OR 0.84, 95% CI 0.58-1.22), while DMPA injection was possibly linked to a higher risk of falling glucose status postpartum (OR 1.42, 95% CI 0.85-2.36). Two studies evaluated high-risk pregnancies and births in contraceptive users versus non-users, with the risk ratio being 30% lower among contraceptive users of any form (95% CI 0.61, 0.80). None of these results were statistically significant except the latter. In terms of adverse maternal health outcomes, certain contraceptives were found to be associated with ectopic pregnancy and pregnancy-related venous thromboembolism through additional analysis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jahanfar et al. This 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.)

Fermentation-based biosynthesis in synthetic biology relies heavily on sugar-derived feedstocks, a limited and carbon-intensive commodity. Unconventional feedstocks from less-noble sources such as waste are being utilized to produce high-value chemical products. Azo dyes, a major pollutant commonly discharged by food, textile, and pharmaceutical industries, present significant health and environmental risks. We explore the potential of engineering Pseudomonas putida KT2440 to utilize azo dyes as a substrate to produce a polyketide, actinorhodin (ACT). Using the constrained minimal cut sets (cMCS) approach, we identified metabolic interventions that optimize ACT biosynthesis and compare the growth-coupling solutions attainable on an azo dye compared to glucose. Our results predicted that azo dyes could perform better as a feedstock for ACT biosynthesis than glucose as it allowed growth-coupling regimes that are unfeasible with glucose and generated an 18.28% higher maximum ACT flux. By examining the flux distributions enabled in different carbon sources, we observed that carbon fluxes from aromatic compounds like azo dyes have a unique capability to leverage gluconeogenesis to support both growth and production of secondary metabolites that produce excess NADH. Carbon sources are commonly chosen based on the host organism, availability, cost, and environmental implications. We demonstrated that careful selection of carbon sources is also crucial to ensure that the resulting flux distribution is suitable for further metabolic engineering of microbial cell factories., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nayyara et al. This 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.)

Background: Observational studies have demonstrated an association between white blood cells (WBC) subtypes and type 2 diabetes (T2D) risk. However, it is unknown whether this relationship is causal. We used Mendelian randomization (MR) to investigate the causal effect of WBC subtypes on T2D and glycemic traits., Methods: The summary data for neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts were extracted from a recent genome-wide association study (n = 173,480). The DIAGRAM and MAGIC consortia offered summary data pertaining to T2D and glycemic characteristics, including fasting glucose (FG) (n = 133,010), glycosylated hemoglobin (HbA1c) (n = 46,368), and homeostatic model assessment-estimated insulin resistance (HOMA-IR) (n = 37,037). A series of MR analyses (univariable MR, multivariable MR, and reverse MR) were used to investigate the causal association of different WBC subtypes with T2D and glycemic traits., Results: Using the inverse-variance weighted method, we found one standard deviation increases in genetically determined neutrophil [odd ratio (OR): 1.086, 95% confidence interval (CI): 0.877-1.345], lymphocyte [0.878 (0.766-1.006)], monocyte [1.010 (0.906-1.127)], eosinophil [0.995 (0.867-1.142)], and basophil [0.960 (0.763-1.207)] were not causally associated with T2D risk. These findings were consistent with the results of three pleiotropy robust methods (MR-Egger, weighted median, and mode-based estimator) and multivariable MR analyses. Reverse MR analysis provided no evidence for the reverse causation of T2D on WBC subtypes. The null causal effects of WBC subtypes on FG, HbA1c, and HOMA-IR were also identified., Conclusions: WBCs play no causal role in the development of insulin resistance and T2D. The observed association between these factors may be explained by residual confounding., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bi et al. This 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 kallikrein–kinin system has been implicated in body weight and glucose homeostasis. Their major effectors act by binding to the kinin B2 and B1 receptors. It was assessed the role of the kinin B1 receptor in weight and glucose homeostasis in B1 receptor knockout mice (B1RKO) subjected to a cafeteria diet (CAF). Wild-type (WT) and B1RKO male mice (C57BL/6 background; 8 weeks old) were fed a standard diet (SD) or CAF for 14 weeks, ad libitum, and four groups were formed: WT-SD; B1RKO-SD; WT-CAF; B1RKO-CAF. Body weight and food intake were assessed weekly. It was performed glucose tolerance (GTT) and insulin tolerance tests (ITT), and HOMA-IR, HOMA-β and HOMA-β* 1/HOMA-IR were calculated. Islets from WT and B1RKO were isolated in order to measure the insulin secretion. Western blot was used to assess the hepatic AKT phosphorylation and qPCR to assess gene expression. CAF induced a higher body mass gain in B1RKO compared to WT mice. CAF diet increased epididymal fat depot mass, hepatic fat infiltration and hepatic AKT phosphorylation in both genotypes. However, B1RKO mice presented lower glycemic response during GTT when fed with CAF, and a lower glucose decrease in the ITT. This higher resistance was overcomed with higher insulin secretion when stimulated by high glucose, resulting in higher glucose uptake in the GTT when submitted to CAF, despite lower insulin sensitivity. Islets from B1RKO delivered 4 times more insulin in 3-month-old mice than islets from WT. The higher insulin disposition index and high insulin delivery of B1RKO can explain the decreased glucose excursion during GTT. In conclusion, CAF increased the β-cell function in B1RKO mice, compensated by the diet-induced insulin resistance and resulting in a healthier glycemic response despite the higher weight gain. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluated hemoglobin A1c (HbA1c), the hemoglobin glycation index (HGI), and triglyceride and glucose (TG) index as predictive indicators for low feed intake in lactating sows due to glucose intolerance. Cactus (Opuntia ficus-indica) was included in sow diets as a modulating factor of glucose. Thirty-six sows were separated into three groups (Gs). Although the three groups received a conventional diet during gestation and lactation, 2.0 kg per sow per day of steam-cooked cactus (G1) and fresh cactus (G2) were added to the lactation diet as a glycemic modulating factor, with G3 serving as the control group. Glycemia was assessed via glucometer (blood glucose concentrations), HbA1c and HGI. For each indicator of glycemia the triglycerides and glucose (TG) index was evaluated. The highest blood glucose concentration was observed on day 3 of lactation (88.2 mg/dL). The average glycemic concentrations obtained from HbA1c on farrowing day (61.6 mg/dL) and day 21 of lactation (65.6 mg/dL) were lower (p<0.05) than those measured by a glucometer on the same days (71.8 and 77.7 mg/dL for farrowing day and day 21 of lactation, respectively). At farrowing, the TG index obtained from the HGI indicated that 83.0% of sows were glucose intolerant, compared to 100% according to the TG index obtained from a glucometer. At weaning, 50% of G2 did not show glucose intolerance when the TG index was calculated using the HGI, compared to 54% when it was calculated with blood glucose concentrations measured by a glucometer. All G3 sows presented glucose intolerance, regardless of the test used. The HbA1c, HGI, and TG index tests are viable alternatives to predict low feed intake due to glucose intolerance in lactating sows. [ABSTRACT FROM AUTHOR]

The degree of maintaining nutrient intake patterns, conformed in the family, for offspring into adulthood is unknown. The aim of this study was to investigate the correlation between nutrient intakes in three younger-middle-older generations of Tehranian adults by sex. Of individuals who participated in 2012–15 phase of the Tehran Lipid and Glucose Study, 1286 families (4685 subjects), who had at least two members of the family with complete data in two or three generations were entered in this cross-sectional study. The energy and nutrient intakes of parents and their young or adult offspring or grandparents-grandson/granddaughter dyads were compared. The differences were estimated using pairwise t-test and partial correlation. Data of parents with their offspring were paired based on living arrangement. There were 857 fathers (mean age: 55.4±11.1) and 1394 mothers (mean age: 50.1±11.4). The mean age of grandfathers and grandmothers were 69.4±7.9 and 63.7±8.5 respectively. The significant correlation in fathers-sons and father-daughter (living with their parents) pairs were observed for 9 and 7 nutrients, respectively. Correlations for most nutrients were significant for mother-daughter or sons (living with their parents) dyads. The mean percentage of energy from total fat and trans-fatty acids of sons or daughters (living with their parents) were higher than their parents. For most nutrients, there were no significant adjusted correlations between parents-adult offspring (living independent of their parents) dyads. Also few nutrient intakes of grandparents-grandson or granddaughter dyads were correlated. The nutrient intakes of adult offspring were not associated with their parents; this correlation for younger and older generations disappeared. There were weak to moderate correlation between nutrient intakes of parent-offspring dyads that lived with their parents. The resemblance was higher for mother-offspring than father-offspring. Overall, total fat and trans-fatty acid intakes of young offspring were higher than their parents. [ABSTRACT FROM AUTHOR]

BACKGROUND: Type-D personality, defined as a combination of high negative affect and high social isolation, has been associated with poor health outcomes. However, pathways underlying this association are largely unknown. We investigated the relationship between Type-D personality and several biological and behavioral pathways including the autonomic nervous system, the immune system, glucose regulation and sleep in a large, apparently healthy sample. METHODS: Data from a total of 646 respondents (age 41.6±11.5, 12,2% women) were available for analysis. Persons with Type-D (negative affect and social isolation score ≥10) were contrasted with those without Type-D. Measures of plasma fibrinogen levels, white blood cell count, high sensitivity C-reactive protein, fasting plasma glucose (FPG), cholesterol, high-density and low-density lipoprotein, glycated hemoglobin (HbA1c), creatinine, triglycerides, and albumin were derived from fasting blood samples. Urine norepinephrine and free cortisol were determined by high-performance liquid chromatography. Time-domain heart rate variability (HRV) measures were calculated for the 24hr recording period and for nighttime separately. RESULTS: Persons with Type-D had higher HbA1c, FPG, and fibrinogen, and lower nighttime HRV than those without Type-D, suggesting worse glycemic control, systemic inflammation and poorer autonomic nervous system modulation in Type-D persons. In addition, those with Type-D reported less social support and greater sleep difficulties while no group differences were observed for alcohol and cigarette consumption, physical activity and body mass index. CONCLUSIONS: Findings provide some of the first evidence for multiple possible biological and behavioral pathways between Type-D personality and increased morbidity and mortality.

Introduction: Sodium fluoride (NaF) tubes are the recommended tubes for glucose measurements, but these are expensive, have limited number of uses, and are not always available in low resource settings. Alternative sample handling techniques are thus needed. We compared glucose stability in samples collected in various tubes exposed to different pre-analytical conditions in Uganda. Methods: Random (non-fasted) blood samples were drawn from nine healthy participants into NaF, Ethylenediaminetetraacetic acid (EDTA), and plain serum tubes. The samples were kept un-centrifuged or centrifuged with plasma or serum pipetted into aliquots, placed in cool box with ice or at room temperature and were stored in a permanent freezer after 0, 2, 6, 12 and 24 hours post blood draw before glucose analysis. Results: Rapid decline in glucose concentrations was observed when compared to baseline in serum (declined to 64%) and EDTA-plasma (declined to 77%) after 6 hours when samples were un-centrifuged at room temperature whilst NaF-plasma was stable after 24 hours in the same condition. Un-centrifuged EDTA-plasma kept on ice was stable for up to 6 hours but serum was not stable (degraded to 92%) in the same conditions. Early centrifugation prevented glucose decline even at room temperature regardless of the primary tube used with serum, EDTA-plasma and NaF-plasma after 24 hours. Conclusion: In low resource settings we recommend use of EDTA tubes placed in cool box with ice and analysed within 6 hours as an alternative to NaF tubes. Alternatively, immediate separation of blood with manual hand centrifuges will allow any tube to be used even in remote settings with no electricity. [ABSTRACT FROM AUTHOR]

Dickeya solani is a pathogen most frequently responsible for infecting potato plants in Europe. As in the case of most plant pathogens, its ability to colonize and invade the host depends on chemotaxis and motility. The coordinated movement of Dickeya over solid surfaces is governed by a quorum sensing mechanism. In D. solani motility is regulated by ExpI-ExpR proteins, homologous to luxI-luxR system from Vibrio fisheri, in which N-acyl-homoserine lactones (AHLs) serve as signaling molecules. Moreover, in many Gram-negative bacteria motility is coupled with central metabolism via carbon catabolite repression. This enables them to reach more nutrient-efficient niches. The aim of this study was to analyze the swarming motility of D. solani depending on the volume of the medium in the cultivation plate and glucose content. We show that the ability of this bacterium to move is strictly dependent on both these factors. Moreover, we analyze the production of AHLs and show that the quorum sensing mechanism in D. solani is also influenced by the availability of glucose in the medium and that the distribution of these signaling molecules are different depending on the volume of the medium in the plate. [ABSTRACT FROM AUTHOR]

Background: Both insulin resistance and postprandial glucose spikes are known for their potential to induce vascular endothelial dysfunction in individuals with metabolic syndrome. However, these factors are inextricable, and therefore, their relative contributions to inducing endothelial dysfunction remain elusive. In this study, we aimed to disentangle the effects of these factors and clarify whether bardoxolone methyl (CDDO-Me), a novel nuclear factor erythroid 2-related factor 2 (Nrf2) activator, protects against glucose spike-induced endothelial dysfunction. Methods: We induced glucose spikes twice daily for a duration of 1 week to rats fed a standard/control diet (CD) and Western-type diet (WTD). Endothelium-dependent relaxation (EDR) was evaluated using isolated thoracic aortas. Gene expression and dihydroethidium (DHE)-fluorescence studies were carried out; the effect of CDDO-Me on aortic endothelial dysfunction in vivo was also evaluated. Results: Neither WTD-induced insulin resistance nor pure glucose spikes significantly deteriorated EDR. However, under high-glucose (20 mM) conditions, the EDR of thoracic aortas of WTD-fed rats subjected to glucose spikes was significantly impaired. In this group of rats, we observed significantly enhanced DHE fluorescence as a marker of reactive oxygen species, upregulation of an oxidative stress-related gene (NOX2), and downregulation of an antioxidant gene (SOD2) in the thoracic aortas. As expected, treatment of the thoracic aorta of this group of rats with antioxidant agents significantly improved EDR. We also noted that pretreatment of aortas from the same group with CDDO-Me attenuated endothelial dysfunction, accompanied by a correction of the redox imbalance, as observed in gene expression and DHE fluorescence studies. Conclusions: For the first time, we showed that insulin resistance and glucose spikes exert a synergistic effect on aortic endothelial dysfunction. Furthermore, our study reveals that CDDO-Me ameliorates endothelial dysfunction caused by glucose spikes in a rat model of metabolic syndrome. [ABSTRACT FROM AUTHOR]

The interaction between plant, soil and microorganism plays a crucial role in sustainable development of terrestrial ecosystem function and diversity. However, little information is known about how plant growth, soil organic carbon (C) fractions and microorganism respond to exogenous C addition in soils with low organic C content. Three levels of 13C-glucose (equal to 0, 100% and 500% of initial microbial biomass C) were added to non-sterilized (corresponding to treatment abbreviation of CK, Glu-1, Glu-2, respectively) and sterilized soils (corresponding to treatment abbreviation of SS, SS+Glu-1, SS+Glu-2, respectively) planted with apple rootstock (Malus baccata (L.) Borkh.) seedings. The objectives of this study were to analyse the dynamics of soil organic C (SOC) fractions and soil bacterial community diversity with glucose levels and soil sterilization, and to explore the morphology of roots and nitrogen (N) metabolism by plant after glucose addition to sterilized/non-sterilized soils. Results showed that the contents of labile organic C fractions were significantly varied (P<0.05) with the levels of glucose addition and soil sterilization. SS+Glu-2 and Glu-2 treatments increased the contents of labile organic C fractions, on average, by 48.47% and 35.33% compared with no glucose addition, respectively. About 21.42% and 16.17% of glucose-C remained in sterilized and non-sterilized soils, respectively at the end of experiment (day 45). Regardless of soil sterilized or not, the glucose addition increased the richness and diversity indices of soil bacterial community compared with no-glucose addition. The glucose addition optimized root zone conditions, and enhanced root vitality, morphology and biomass. Both SS+Glu-2 and Glu-2 treatments significantly enhanced (P<0.05) the contents of nitrate (NO3—N) and nitrite (NO2—N), but sharply decreased (P<0.05) the ammonium (NH4+-N) content compared with no glucose addition. Also, these two treatments significantly (P<0.05) increased the enzymic activities and gene transcript levels involved in root N metabolism, which demonstrated that the high level of glucose addition promoted N assimilation and transformation into free amino acids by root. Overall, the addition of exogenous C to not only promotes its fixation and bacterial community diversity in C-poor soils, but also improves root morphology and N absorption by plant. [ABSTRACT FROM AUTHOR]

Skeletal muscle secretes factors, termed myokines. We employed differentiated human skeletal muscle cells (hSMC) cultured from Type 2 diabetic (T2D) and non-diabetic (ND) subjects to investigate the impact of T2D on myokine secretion. Following 24 hours of culture concentrations of selected myokines were determined to range over 4 orders of magnitude. T2D hSMC released increased amounts of IL6, IL8, IL15, TNFa, Growth Related Oncogene (GRO)a, monocyte chemotactic protein (MCP)-1, and follistatin compared to ND myotubes. T2D and ND hSMC secreted similar levels of IL1ß and vascular endothelial growth factor (VEGF). Treatment with the inflammatory agents lipopolysaccharide (LPS) or palmitate augmented the secretion of many myokines including: GROa, IL6, IL8, IL15, and TNFa, but did not consistently alter the protein content and/or phosphorylation of IkBa, p44/42 MAPK, p38 MAPK, c-Jun N-terminal kinase (JNK) and NF-kB, nor lead to consistent changes in basal and insulin-stimulated glucose uptake or free fatty acid oxidation. Conversely, treatment with pioglitazone or oleate resulted in modest reductions in the secretion of several myokines. Our results demonstrate that altered secretion of a number of myokines is an intrinsic property of skeletal muscle in T2D, suggesting a putative role of myokines in the response of skeletal muscle to T2D.