Explore the vast range of titles available.

Hypoglycaemia (low plasma glucose) is a serious and potentially fatal complication of insulin-treated diabetes. In healthy individuals, hypoglycaemia triggers glucagon secretion, which restores normal plasma glucose levels by stimulation of hepatic glucose production. This counterregulatory mechanism is impaired in diabetes. Here we show in mice that therapeutic concentrations of insulin inhibit glucagon secretion by an indirect (paracrine) mechanism mediated by stimulation of intra-islet somatostatin release. Insulin’s capacity to inhibit glucagon secretion is lost following genetic ablation of insulin receptors in the somatostatin-secreting δ-cells, when insulin-induced somatostatin secretion is suppressed by dapagliflozin (an inhibitor of sodium-glucose co-tranporter-2; SGLT2) or when the action of secreted somatostatin is prevented by somatostatin receptor (SSTR) antagonists. Administration of these compounds in vivo antagonises insulin’s hypoglycaemic effect. We extend these data to isolated human islets. We propose that SSTR or SGLT2 antagonists should be considered as adjuncts to insulin in diabetes therapy. Impaired glucagon secretion in patients with diabetes causes hypoglycemia. Here the authors show that therapeutic concentrations of insulin inhibit alpha-cell glucagon secretion by stimulating delta-cell insulin receptor and the release of somatostatin. Blocking somatostatin secretion or action ameliorates this effect.

Diabetes is characterized by hyperglycaemia due to impaired insulin secretion and aberrant glucagon secretion resulting from changes in pancreatic islet cell function and/or mass. The extent to which hyperglycaemia per se underlies these alterations remains poorly understood. Here we show that β-cell-specific expression of a human activating K ATP channel mutation in adult mice leads to rapid diabetes and marked alterations in islet morphology, ultrastructure and gene expression. Chronic hyperglycaemia is associated with a dramatic reduction in insulin-positive cells and an increase in glucagon-positive cells in islets, without alterations in cell turnover. Furthermore, some β-cells begin expressing glucagon, whilst retaining many β-cell characteristics. Hyperglycaemia, rather than K ATP channel activation, underlies these changes, as they are prevented by insulin therapy and fully reversed by sulphonylureas. Our data suggest that many changes in islet structure and function associated with diabetes are attributable to hyperglycaemia alone and are reversed when blood glucose is normalized. In patients with diabetes, insulin release from pancreatic β-cells is reduced due to altered islet structure and function. Here, Brereton et al . show that elevated blood glucose underlies these changes and is sufficient to reversibly alter β-cell identity in a mouse model of β-cell dysfunction.

International research highlights the potentially valuable contribution of outdoor education to the healthy development and proper holistic education of students. Among the various benefits that students gain from participating in outdoor activities are the mitigation of symptoms of Attention Deficit Hyperactivity Disorder (ADHD), improved respiration, memory improvement, skills development and others. Despite the well-documented contribution of such activities to children’s wellbeing, there is an increasing trend of younger children lacking contact with nature. The current study investigates to what extent teachers in Greece, at schools where students aged 6–18 attend, provide opportunities for outdoor activities to their students. Furthermore, it investigates the teacher’s perceptions of the benefits the students gain from such activities, based on their personal experience and the experience of other co-teachers in their school. The results presented in this study indicate that the percentage of teachers who choose outdoor activities during the educational process in Greece is rather low, although they identify that such activities provide significant benefits to students. Based on the perceptions of teachers regarding the mental, cognitive and physical benefits that students gain from outdoor activities a positive association was found between the participation of students in such activities and these benefits. Therefore, this study reveals that it is of significant importance to increase the number of opportunities for students’ participation in outdoor learning activities, by supporting teachers, creating learning communities with them and empowering them to provide more outdoor learning opportunities.

Glucagon secretion by pancreatic α-cells is triggered by hypoglycemia and suppressed by high glucose levels; impaired suppression of glucagon secretion is a hallmark of both type 1 and type 2 diabetes. Here, we show that α-cell glucokinase ( Gck ) plays a role in the control of glucagon secretion. Using mice with α-cell-specific inactivation of Gck ( αGckKO mice), we find that glucokinase is required for the glucose-dependent increase in intracellular ATP/ADP ratio and the closure of K ATP channels in α-cells and the suppression of glucagon secretion at euglycemic and hyperglycemic levels. αGckKO mice display hyperglucagonemia in the fed state, which is associated with increased hepatic gluconeogenic gene expression and hepatic glucose output capacity. In adult mice, fed hyperglucagonemia is further increased and glucose intolerance develops. Thus, glucokinase governs an α-cell metabolic pathway that suppresses secretion at or above normoglycemic levels; abnormal suppression of glucagon secretion deregulates hepatic glucose metabolism and, over time, induces a pre-diabetic phenotype. Glucagon secretion is promoted during hypoglycemia and inhibited by increased glucose levels. Here, Basco et al. show that glucokinase suppresses glucose-regulated glucagon secretion by modulating the intracellular ATP/ADP ratio and the closure of K ATP channels in α-cells.

Background Type 1 diabetes mellitus (T1DM) is characterized by immune and metabolic dysregulation. Apo1/Fas is implicated in maintaining homeostasis of the immune system. Cytokeratin-18 (cCK-18) is a predictive marker of liver disorders in T2DM. Intercellular adhesion molecule-1 (ICAM-1) is considered to increase susceptibility to diabetes mellitus. All three markers are associated with endothelial function, apoptosis and diabetes-related complications. The possible role of Apo1/Fas, cCK-18 and ICAM-1 was investigated in children and adolescents with T1DM. Method Forty-nine (49) children and adolescents with T1DM and 49 controls were included in the study. Somatometric measurements were obtained and the Body Mass Index (BMI) of the participants was calculated. Biochemical parameters were measured by standard laboratory methods and Apo1/Fas, cCK-18 and ICAM-1 were measured using appropriate ELISA kits. The statistical analysis was performed using the IBM SPSS Statistics 23 program. Results Apo1/Fas ( p  = 0.001), cCK-18 ( p  < 0.001) and ICAM-1 ( p  < 0.001) were higher in patients with T1DM compared to the controls. Apo1Fas was negatively correlated with glucose ( p  = 0.042), uric acid ( p  = 0.026), creatinine ( p  = 0.022), total cholesterol ( p  = 0.023) and LDL ( p  = 0.005) in the controls. In children and adolescents with T1DM, Apo1/Fas was positively correlated with total cholesterol ( p  = 0.013) and LDL ( p  = 0.003). ICAM-1 was negatively correlated with creatinine ( p  = 0.019) in the controls, whereas in patients with T1DM it was negatively correlated with HbA1c ( p  = 0.05). Conclusions Apo1/Fas, cCK-18 and ICAM-1 may be useful as serological markers for immune and metabolic dysregulation in children and adolescents with T1DM. Also, Apo1/Fas may have a protective role against metabolic complications in healthy children.

Soil salinization is directly related to the quantity and quality of food production, and often, to increased energy demands for high-quality irrigation water. Reliable monitoring of soil salinity based on a less laborious method than the soil saturated paste (SP) extract methodology is required. In the present study, an attempt is made to relate the electrical conductivity (EC) of the soil saturated paste (SP) extract (ECe) with the EC determined in the 1:1 and 1:5 soil over water mass ratios, (soil:water) extracts (EC1:1 and EC1:5). ECe, EC1:1, and EC1:5 values were obtained for 198 soil samples from five different locations in Greece. The results have shown that strong linear relationships exist between the ECe and the EC1:1 and EC1:5 values (R2 > 0.93), and that the slopes of these linear relationships decreased from coarse to fine soil types. For 123 soil samples, the concentrations of Κ+, Νa+, Ca2+, Mg2+, and Cl− were also determined in the extracts of the three applied methodologies. Ion concentrations in the 1:1 and 1:5 extracts were highly correlated with the respective ion concentrations in the SP extracts. These findings strongly suggest that EC1:1 and EC1:5 values can be safely used for the estimation of ECe.

This paper studies, through the principles of fuzzy set theory, groundwater response to meteorological drought in the case of an aquifer system located in the plains at the southeast of Xanthi, NE Greece. Meteorological drought is expressed through standardized Reconnaissance Drought Index (RDISt) and Standardized Precipitation Index (SPI), which are calculated for various reference periods. These drought indices are considered as independent variables in multiple fuzzy linear regression based on Tanaka's model, while the observed water table regarding two areas is used as a dependent variable. The fuzzy linear regression of Tanaka is characterized by the inclusion constraints where all the observed data must be included in the produced fuzzy band. Hence, each fuzzy output can get an interval of values where a membership degree corresponds to each of them. A modification of the Tanaka model by adding constraints is proposed in order to avoid irrational behavior. The results show that there was a significant influence of the meteorological drought of the previous hydrological year, while geology plays an important role. Furthermore, the use of RDISt improves the results of fuzzy linear regressions in all cases. Two suitability measures and a measure of comparison between fuzzy numbers are used.

To investigate the effect of leptin in childhood ITP, we measured plasma leptin in 39 children with acute ITP, after treatment and in remission, and in 33 healthy age/BMI-matched controls. We also cultured ITP and control peripheral blood mononuclear cells (PBMCs) with recombinant leptin to assess its direct effect on pro/anti-inflammatory cytokine gene expression. A significant increase in leptin was observed in children with active disease compared to controls. A significant inverse correlation of leptin with platelet count was also observed in children with acute ITP. Leptin remained high after treatment with IVIg, whereas steroid treatment lowered leptin below control levels. In remission, leptin was in the control range. Cytokine gene expression was significantly increased in children with acute ITP compared with controls, with highest expression for IFN-γ and IL-10. IVIg/steroid treatment significantly decreased IFN-γ and IL-10 expression. In remission, IFN-γ and IL-10 expression remained low. Addition of leptin to PBMCs isolated from patients in remission resulted in a significant increase in IL-10 gene expression compared to controls. Further experiments with purified T-cells and monocytes identified monocytes as the source of leptin-induced IL-10. We suggest that leptin acts as an active anti-inflammatory agent in childhood ITP by promoting IL-10 secretion by monocytes.

Background The prevention of type 2 diabetes (T2DM) is recognised as a health care priority in the UK. In people living with T2DM, lifestyle changes (e.g. increasing physical activity) have been shown to slow disease progression and protect from the development of associated comorbidities. The use of digital health technologies provides a strategy to increase physical activity in patients with chronic disease. Furthermore, behaviour economics suggests that financial incentives may be a useful strategy for increasing the maintenance and effectiveness of behaviour change intervention, including physical activity intervention using digital health technologies. The Milton Keynes Activity Rewards Programme (MKARP) is a 24-month intervention which combines the use of a mobile health app, smartwatch (Fitbit or Apple watch) and financial incentives to encourage people living with T2DM to increase physical activity to improve health. Therefore, this randomised controlled trial aims to examine the long-term acceptability, health effects and cost-effectiveness of the MKARP on HbA1c in patients living with T2DM versus a waitlist usual care comparator. Methods A two-arm, single-centre, randomised controlled trial aiming to recruit 1018 participants with follow-up at 12 and 24 months. The primary outcome is the change in HbA1c at 12 months. Secondary outcomes included changes in markers of metabolic, cardiovascular, anthropometric, and psychological health along with cost-effectiveness. Recruitment will be via annual diabetes review in general practices, retinal screening services and social media. Participants aged 18 or over, with a diagnosis of type 2 diabetes and a valid HbA1c measurement in the last 2 months are invited to take part in the trial. Participants will be individually randomised (1:1 ratio) to receive either the Milton Keynes Activity Rewards Programme or usual care. The intervention will last for 24 months with assessment for outcomes at baseline, 12 and 24 months. Discussion This study will provide new evidence of the long-term effectiveness of an activity rewards scheme focused on increasing physical activity conducted within routine care in patients living with type 2 diabetes in Milton Keynes, UK. It will also investigate the cost-effectiveness of the intervention. Trial registration ISRCTN 14925701. Registered on 30 October 2023.