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In patients with drug-resistant epilepsy, difficulties in identifying the epileptogenic zone are well known to correlate with poorer clinical outcomes post-surgery. The integration of PET and MRI in the presurgical assessment of pediatric patients likely improves diagnostic precision by confirming or widening treatment targets. PET and MRI together offer superior insights compared to either modality alone. For instance, PET highlights abnormal glucose metabolism, while MRI precisely localizes structural anomalies, providing a comprehensive understanding of the epileptogenic zone. Furthermore, both methodologies, whether utilized through simultaneous PET/MRI scanning or the co-registration of separately acquired PET and MRI data, present unique advantages, having complementary roles in lesional and non-lesional cases. Simultaneous FDG-PET/MRI provides precise co-registration of functional (PET) and structural (MR) imaging in a convenient one-stop-shop approach, which minimizes sedation time and reduces radiation exposure in children. Commercially available fusion software that allows retrospective co-registration of separately acquired PET and MRI images is a commonly used alternative. This review provides an overview and illustrative cases that highlight the role of combining 18F-FDG-PET and MRI imaging and shares the authors' decade-long experience utilizing simultaneous PET/MRI in the presurgical evaluation of pediatric epilepsy. [ABSTRACT FROM AUTHOR]

Background: Cotton is an important economic crop and a host of Liriomyza sativae. Pectin methylesterase (PME)-mediated pectin metabolism plays an indispensable role in multiple biological processes in planta. However, the pleiotropic functions of PME often lead to unpredictable effects on crop resistance to pests. Additionally, whether and how PME affects susceptibility to Liriomyza sativae remain unclear. Results: Here, we isolated GhPME36, which is located in the cell wall, from upland cotton (Gossypium hirsutum L.). Interestingly, the overexpression of GhPME36 in cotton caused severe susceptibility to Liriomyza sativae but increased leaf biomass in Arabidopsis. Cytological observations revealed that the cell wall was thinner with more demethylesterified pectins in GhPME36-OE cotton leaves than in WT leaves, whereas the soluble sugar content of GhPME36-OE cotton leaf cell walls was accordingly higher; both factors attracted Liriomyza sativae to feed on GhPME36-OE cotton leaves. Metabolomic analysis demonstrated that glucose was significantly differentially accumulated. Transcriptomic analysis further revealed DEGs enriched in glucose metabolic pathways when GhPME36 was overexpressed, suggesting that GhPME36 aggravates susceptibility to Liriomyza sativae by affecting both the structure and components of cell wall biosynthesis. Moreover, GhPME36 interacts with another pectin-modifying enzyme, GhC/VIF1, to maintain the dynamic stability of pectin methyl esterification. Conclusions: Taken together, our results reveal the cytological and molecular mechanisms by which GhPME36 aggravates susceptibility to Liriomyza sativae. This study broadens the knowledge of PME function and provides new insights into plant resistance to pests and the safety of genetically modified plants. [ABSTRACT FROM AUTHOR]

Key points There is evidence that aerobic exercise improves brain health. Benefits may be modulated by acute physiological responses to exercise, but this has not been well characterized in older or cognitively impaired adults. The randomized controlled trial ‘AEROBIC’ (NCT04299308) enrolled 60 older adults who were cognitively healthy (n = 30) or cognitively impaired (n = 30) to characterize the acute brain responses to moderate [45–55% heart rate reserve (HRR)] and higher (65–75% HRR) intensity acute exercise. Each participant received two fluorodeoxyglucose positron emission tomography (FDG‐PET) scans, one at rest and one following acute exercise. Change in cerebral glucose metabolism from rest to exercise was the primary outcome. Blood biomarker responses were also characterized as secondary outcomes. Whole grey matter FDG‐PET standardized uptake value ratio (SUVR) differed between exercise (1.045 ± 0.082) and rest (0.985 ± 0.077) across subjects [Diff = −0.060, t(58) = 13.8, P < 0.001] regardless of diagnosis. Exercise increased lactate area under the curve (AUC) [F(1,56) = 161.99, P < 0.001] more in the higher intensity group [mean difference (MD) = 97.0 ± 50.8] than the moderate intensity group (MD = 40.3 ± 27.5; t = −5.252, P < 0.001). Change in lactate AUC and FDG‐PET SUVR correlated significantly (R2 = 0.179, P < 0.001). Acute exercise decreased whole grey matter cerebral glucose metabolism. This effect tracked with the systemic lactate response, suggesting that lactate may serve as a key brain fuel during exercise. Direct measurements of brain lactate metabolism in response to exercise are warranted. Acute exercise is associated with a drop in global brain glucose metabolism in both cognitively healthy older adults and those with Alzheimer's disease. Blood lactate levels increase following acute exercise. Change in brain metabolism tracks with blood lactate, suggesting it may be an important brain fuel. Acute exercise stimulates changes in brain‐derived neurotrophic factor and other blood biomarkers. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common form of dementia. Although drugs focusing on reducing amyloid β slow progression, they fail to improve cognitive function. Deficits in glucose metabolism are reflected in FDG-PET and parallel the neurodegeneration and synaptic marker loss closely preceding cognitive decline, but the role of metabolic deficits as a cause or consequence of neurodegeneration is unclear. Pyruvate dehydrogenase (PDH) is lost in AD and an important enzyme connecting glycolysis and the tricarboxylic acid (TCA) cycle by converting pyruvate into acetyl-CoA. It is negatively regulated by pyruvate dehydrogenase kinase (PDHK) through phosphorylation. Methods: In the present study, we assessed the in vitro/ in vivo pharmacological profile of the novel PDHK inhibitor that we discovered, Compound A. We also assessed the effects of Compound A on AD-related phenotypes including neuron loss and cognitive impairment using 5xFAD model mice. Results: Compound A inhibited human PDHK1, 2 and 3 but had no inhibitory activity on PDHK4. In primary neurons, Compound A enhanced pyruvate and lactate utilization, but did not change glucose levels. In contrast, in primary astrocytes, Compound A enhanced pyruvate and glucose utilization and enhanced lactate production. In an efficacy study using 5xFAD mice, Compound A ameliorated the cognitive dysfunction in the novel object recognition test and Morris water maze. Moreover, Compound A prevented neuron loss in the hippocampus and cerebral cortex of 5xFAD without affecting amyloid β deposits. Conclusions: These results suggest ameliorating metabolic deficits by activating PDH by Compound A can limit neurodegeneration and is a promising therapeutic strategy for treating AD. [ABSTRACT FROM AUTHOR]

Bioenergy decline occurs with reperfusion following acute ischemic stroke. However, the molecular mechanisms that limit energy metabolism and their impact on post-stroke cognitive and emotional complications are still unclear. In the present study, we demonstrate that the p53 transcriptional response is responsible for neuronal adenosine triphosphate (ATP) deficiency and progressively neuropsychiatric disturbances, involving the downregulation of mitochondrial voltage-dependent anion channels (VDACs). Neuronal p53 transactivated the promoter of microRNA-183 (miR-183) cluster, thereby upregulating biogenesis of miR-183-5p (miR-183), miR-96-5p (miR-96), and miR-182-5p. Both miR-183 and miR-96 directly targeted and post-transcriptionally suppressed VDACs. Neuronal ablation of p53 protected against ATP deficiency and neurological deficits, whereas post-stroke rescue of miR-183/VDAC signaling reversed these benefits. Interestingly, cyclin-dependent kinase 9 (CDK9) was found to be enriched in cortical neurons and upregulated the p53-induced transcription of the miR-183 cluster in neurons after ischemia. Post-treatment with the CDK9 inhibitor oroxylin A promoted neuronal ATP production mainly through suppressing the miR-183 cluster/VDAC axis, further improved long-term sensorimotor abilities and spatial memory, and alleviated depressive-like behaviors in mice following stroke. Our findings reveal an intrinsic CDK9/p53/VDAC pathway that drives neuronal bioenergy decline and underlies post-stroke cognitive impairment and depression, thus highlighting the therapeutic potential of oroxylin A for better outcomes. [ABSTRACT FROM AUTHOR]

Background: Despite the detrimental impact of abnormal glucose metabolism on cardiovascular prognosis after myocardial infarction (MI), diabetes is both underdiagnosed and undertreated. We investigated associations between structured diabetes care routines in cardiac rehabilitation (CR) and detection and treatment of diabetes at one-year post-MI. Methods: Center-level data was derived from the Perfect-CR survey, which evaluated work routines applied at Swedish CR centers (n = 76). Work routines involving diabetes care included: (1) routine assessment of fasting glucose and/or HbA1c, (2) routine use of oral glucose tolerance test (OGTT), (3) having regular case rounds with diabetologists, and (4) whether glucose-lowering medication was adjusted by CR physicians. Patient-level data was obtained from the national MI registry SWEDEHEART (n = 7601, 76% male, mean age 62.6 years) and included all post-MI patients irrespective of diabetes diagnosis. Using mixed-effects regression we estimated differences between patients exposed versus. not exposed to the four above-mentioned diabetes care routines. Outcomes were newly detected diabetes and the proportion of patients receiving oral glucose-lowering medication at one-year post-MI. Results: Routine assessment of fasting glucose/HbA1c was performed at 63.2% (n = 48) of the centers, while 38.2% (n = 29) reported using OGTT for detecting glucose abnormalities. Glucose-lowering medication adjusted by CR physicians (n = 13, 17.1%) or regular case rounds with diabetologists (n = 7, 9.2%) were less frequently reported. In total, 4.0% of all patients (n = 304) were diagnosed with diabetes during follow-up and 17.9% (n = 1361) were on oral glucose-lowering treatment one-year post-MI. Routine use of OGTT was associated with a higher rate of newly detected diabetes at one-year (risk ratio [95% confidence interval]: 1.62 [1.26, 1.98], p = 0.0007). At one-year a higher proportion of patients were receiving oral glucose-lowering medication at centers using OGTT (1.22 [1.07, 1.37], p = 0.0046) and where such medication was adjusted by CR physicians (1.31 [1.06, 1.56], p = 0.0155). Compared to having none of the structured diabetes care routines, the more routines implemented the higher the rate of newly detected diabetes (from 0 routines: 2.7% to 4 routines: 6.3%; p for trend = 0.0014). Conclusions: Having structured routines for diabetes care implemented within CR can improve detection and treatment of diabetes post-MI. A cluster-randomized trial is warranted to ascertain causality. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions The aim was to investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes.A retrospective observational study and a Mendelian randomization (MR) study were used. Observational analyses were performed using data from 4717 Chinese children and adolescents aged 6–18 years who underwent dual‐energy X‐ray absorptiometry for body composition. MR analyses were based on summary statistics from UK Biobank, deCODE2021, Meta‐Analysis of Glucose and Insulin‐Related Traits Consortium (MAGIC) and other large consortiums. Inflammatory biomarkers included leptin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH).In a retrospective observational study, increased fat mass had a positive effect on homeostasis model assessment of insulin resistance (HOMA‐IR) and homeostasis model assessment of pancreatic beta cell function (HOMA‐β) through FGF23, whereas fat‐free mass produced the opposite effects. PTH and osteocalcin played significant roles in the association of fat mass and fat‐free mass with fasting glucose, fasting insulin and HOMA‐IR (all p < 0.05). Mediation MR results indicated that childhood body mass index affected glycaemic traits through leptin and adiponectin. There existed a causal effect of fat‐free mass on type 2 diabetes via FGF23 (indirect effect: OR [odds ratio]: 1.14 [95% CI, confidence interval: 1.01–1.28]) and adiponectin (OR: 0.85 [95% CI: 0.77–0.93]). Leptin mediated the causal association of fat mass (indirect effect: β: −0.05 [95% CI: −0.07, −0.02]) and fat‐free mass (β: 0.03 [95% CI: 0.01, 0.04]) with fasting glucose.Our findings suggest that different body compositions have differential influences on glycaemic traits and type 2 diabetes through distinct inflammatory biomarkers. The findings may be helpful in tailoring management of body composition based on inflammatory biomarkers with different glycaemic statuses. [ABSTRACT FROM AUTHOR]

Continuous glucose monitoring (CGM) is a promising, minimally invasive alternative to plasma glucose measurements for calibrating physiology-based mathematical models of insulin-regulated glucose metabolism, reducing the reliance on in-clinic measurements. However, the use of CGM glucose, particularly in combination with insulin measurements, to develop personalized models of glucose regulation remains unexplored. Here, we simultaneously measured interstitial glucose concentrations using CGM as well as plasma glucose and insulin concentrations during an oral glucose tolerance test (OGTT) in individuals with overweight or obesity to calibrate personalized models of glucose-insulin dynamics. We compared the use of interstitial glucose with plasma glucose in model calibration, and evaluated the effects on model fit, identifiability, and model parameters' association with clinically relevant metabolic indicators. Models calibrated on both plasma and interstitial glucose resulted in good model fit, and the parameter estimates associated with metabolic indicators such as insulin sensitivity measures in both cases. Moreover, practical identifiability of model parameters was improved in models estimated on CGM glucose compared to plasma glucose. Together these results suggest that CGM glucose may be considered as a minimally invasive alternative to plasma glucose measurements in model calibration to quantify the dynamics of glucose regulation. [ABSTRACT FROM AUTHOR]

To evaluate the prognostic significance of the maximum standardized uptake value (SUVmax) in nasopharyngeal carcinoma (NPC), establish a gene signature that correlates with SUVmax, and explore the underlying biological behaviors associated with these correlations for the prediction of clinical outcomes. A cohort of 726 patients with NPC was examined to identify correlations between SUVmax and various clinical variables. RNA sequencing was performed to identify genes related to SUVmax, and these genes were used to develop an SUV signature. Additionally, transcriptome enrichment analysis was conducted to investigate the potential biological behaviors underlying the observed correlations. Higher SUVmax was associated with an increased tumor burden and worse prognosis. The SUV signature, which consisted of 10 genes, was positively correlated with SUVmax, and it predicted worse survival outcomes. This signature was highly expressed in malignant epithelial cells and associated with hypoxia and resistance to radiotherapy. Additionally, the signature was negatively correlated with immune function. SUVmax is a valuable prognostic indicator in NPC, with higher values predicting worse outcomes. The SUV signature offers further prognostic insights, linking glucose metabolism to tumor aggressiveness, treatment resistance, and immune function, and it could represent a potential biomarker for NPC. [ABSTRACT FROM AUTHOR]

Objective: Disorders of glucose metabolism in children with obesity are less common than in adults. There is also evidence that they may be transient. The aims of this study were to determine the prevalences of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (DM2) and its reversibility in pediatric patients with obesity and to define the factors determining the reversibility of prediabetes or progression to diabetes. Methods: Retrospective analysis included of young patients with obesity. Patients presented and were treated between 2000-2022 at a single center. Results: The study included 573 (316 girls; 55.15%) Caucasian patients with median body mass index (BMI) Z-score of 3.95 (range 2.0-9.9) and median age 13.9 (2.9-17.1) years old. OGTT results were normal in 90.8% (n=520) and signs of prediabetes occurred in 9.2% (n=53); IFG 17%, IGT 88.7%, DM 0%. Among those who underwent OGTT twice (n=53), impaired glucose regulation was present in 9.3% (n=5) (IFG 40%, IGT 80%, DM 0%) at baseline and in 14.8% subject (n=8) (IFG 25%, IGT 50%, DM 25%) at follow-up after lifestyle modification only. After 12-36 months of follow up, in those with a history of IGT, 60% reverted to normal glucose tolerance, while IFG and IGT persisted in 20% and 20%, respectively, and none progressed to DM. The risk factors for progression of glucose metabolism disorders were increase of BMI Z-score, higher insulin levels and elevated homeostatic model assessment-insulin resistance. Conclusion: IFG and IGT are common in pediatric patients with obesity, while the progression to DM2 is rare. Disorders of glucose metabolism have reversible character. [ABSTRACT FROM AUTHOR]

Chromosomal abnormalities that involve the MYCN gene are rare; however, it is one of the most commonly mutated genes in retinoblastoma (RB) after the RB1 gene. MYCN is amplified in approximately 1–9 % of all RB tumors. It plays a role in RB oncogenesis via many mechanisms, including synergism with RB1 deletion, positive feedback with MDM2, upregulation of cell cycle regulating genes, upregulation of miRNA, and upregulation of glucose metabolism. MYCN amplifications are not mutually exclusive and can occur even in the presence of RB1 gene mutations. Clinically, RB1+/+MYCNA tumors present as sporadic, unilateral, advanced tumors in very young children and tend to follow an aggressive course. Magnetic resonance imaging features include peripheral tumor location, placoid configuration, retinal folding, tumor-associated hemorrhage, and anterior chamber enhancement. Genetic testing for MYCNA is especially recommended in patients with unilateral RB where genetic blood testing and tumor tissue show a lack of RB1 mutation. MYCN-targeted therapies are evolving and hold promise for the future. [ABSTRACT FROM AUTHOR]

Mammalian cells utilize glucose as a primary carbon source to produce energy for most cellular functions. However, the bioenergetic homeostasis of cells can be perturbed by environmental alterations, such as changes in oxygen levels which can be associated with bacterial infection. Reduction in oxygen availability leads to a state of hypoxia, inducing numerous cellular responses that aim to combat this stress. Importantly, hypoxia strongly augments cellular glycolysis in most cell types to compensate for the loss of aerobic respiration. Understanding how this host cell metabolic adaptation to hypoxia impacts the course of bacterial infection will identify new anti-microbial targets. This review will highlight developments in our understanding of glycolytic substrate channeling and spatiotemporal enzymatic organization in response to hypoxia, shedding light on the integral role of the hypoxia-inducible factor (HIF) during host–pathogen interactions. Furthermore, the ability of intracellular and extracellular bacteria (pathogens and commensals alike) to modulate host cellular glucose metabolism will be discussed. [ABSTRACT FROM AUTHOR]

Transmembrane prolyl 4-hydroxylase (P4H-TM) is an enigmatic enzyme whose cellular function and primary substrate remain to be identified. Its loss-of-function mutations cause a severe neurological HIDEA syndrome with hypotonia, intellectual disability, dysautonomia and hypoventilation. Previously, P4H-TM deficiency in mice was associated with reduced atherogenesis and lower serum triglyceride levels. Here, we characterized the glucose and lipid metabolism of P4h-tm−/− mice in physiological and tissue analyses. P4h-tm−/− mice showed variations in 24-h oscillations of energy expenditure, VO2 and VCO2 and locomotor activity compared to wild-type (WT) mice. Their rearing activity was reduced, and they showed significant muscle weakness and compromised coordination. Sedated P4h-tm−/− mice had better glucose tolerance, lower fasting insulin levels, higher fasting lactate levels and lower fasting free fatty acid levels compared to WT. These alterations were not present in conscious P4h-tm−/− mice. Fasted P4h-tm−/− mice presented with faster hepatic glycogenolysis. The respiratory rate of conscious P4h-tm−/− mice was significantly lower compared to the WT, the decrease being further exacerbated by sedation and associated with acidosis and a reduced ventilatory response to both hypoxia and hypercapnia. P4H-TM deficiency in mice is associated with alterations in whole-body energy metabolism, day-night rhythm of activity, glucose homeostasis and neuromuscular and respiratory functions. Although the underlying mechanism(s) are not yet fully understood, the phenotype appears to have neurological origins, controlled by brain and central nervous system circuits. The phenotype of P4h-tm−/− mice recapitulates some of the symptoms of HIDEA patients, making this mouse model a valuable tool to study and develop tailored therapies. [ABSTRACT FROM AUTHOR]

Aims: The aims of our study were to evaluate whether point‐of‐care β‐hydroxybutyrate (BHB) measurement can be used to identify patients with adequate cardiac glucose metabolism suppression for cardiac [18F]‐fluoro‐2‐deoxy‐d‐glucose‐positron emission tomography with computerized tomography (FDG‐PET/CT) and to develop a pretest probability calculator of myocardial suppression using other metabolic factors attainable before imaging. Methods and Results: We recruited 193 patients with any clinical indication for whole body [18F]‐FDG‐PET/CT. BHB level was measured with a point‐of‐care device. Maximal myocardial standardized uptake value using lean body mass (SULmax) was measured from eight circular regions of interest with 1 cm circumference and background from left ventricular blood pool. Correlations SULmax and point‐of‐care measured BHB were analysed. The ability of BHB test to predict adequate suppression was evaluated with receiver operating characteristic analysis. Liver and spleen attenuation in computed tomography were measured to assess the presence of fatty liver. BHB level correlated with myocardial uptake and, using a cut‐off value of 0.35 mmol/L to predict adequate myocardial suppression, we reached specificity of 90% and sensitivity of 56%. Other variables to predict adequate suppression were diabetes, obesity, ketogenic diet and fatty liver. Using information attainable before imaging, we created a pretest probability calculator of inadequate myocardial glucose metabolism suppression. The area under the curve for BHB test alone was 0.802 and was 0.857 for the pretest calculator (p = 0.319). Conclusions: BHB level measured with a point‐of‐care device is useful in predicting adequate myocardial glucose metabolism suppression. More detailed assessment of other factors potentially contributing to cardiac metabolism is needed. [ABSTRACT FROM AUTHOR]

This study compared brain glucose metabolism using FDG-PET in the caudate nucleus, putamen, globus pallidus, thalamus, and dorsolateral prefrontal cortex (DLPFC) among patients with Long COVID, patients with fatigue, people with multiple sclerosis (PwMS) patients with fatigue, and COVID recovered controls. PwMS exhibited greater hypometabolism compared to long COVID patients with fatigue and the COVID recovered control group in all studied brain areas except the globus pallidus (effect size range 0.7–1.5). The results showed no significant differences in glucose metabolism between patients with Long COVID and the COVID recovered control group in these regions. These findings suggest that long COVID fatigue may involve non-CNS systems, neurotransmitter imbalances, or psychological factors not captured by FDG-PET, while MS-related fatigue is associated with more severe frontal-striatal circuit dysfunction due to demyelination and neurodegeneration. Symmetrical standardized uptake values (SUVs) between hemispheres in all groups imply that fatigue in these conditions may be related to global or network-level alterations rather than hemisphere-specific changes. Future studies should employ fine-grained analysis methods, explore other brain regions, and control for confounding factors to better understand the pathophysiology of fatigue in MS and long COVID. Longitudinal studies tracking brain glucose metabolism in patients with Long COVID could provide insights into the evolution of metabolic patterns as the condition progresses. [ABSTRACT FROM AUTHOR]

Aims: To investigate how a change in body position with light‐intensity physical activity (PA) 'snacks' (LIPAS, alternate sitting and standing, walking or standing continuously) compared with uninterrupted prolonged sitting affects glucose metabolism and heart rate variability (HRV) parameters in young adults with overweight and obesity. Materials and Methods: We conducted a four‐arm randomized controlled crossover trial. The following conditions were tested during an 8‐h simulated workday: uninterrupted prolonged sitting (SIT), alternate sitting and standing (SIT‐STAND; 2.5 h total), continuous standing (STAND), and continuous walking (1.0 mph; WALK). The primary outcome was to investigate how a change in body position (alternate sitting and standing, walking or standing continuously) compared with uninterrupted sitting affects mean 8‐h glucose metabolism. Secondary outcomes included the effects on 2‐h postprandial glucose concentrations, as well as on 8‐h/24‐h heart rate and HRV parameters, in the respective study arms. Capillary blood samples were drawn from an hyperemised earlobe in the fasted state and once every hour during each trial intervention by puncturing the earlobe with a lancet and collecting 20 μL of blood (Biosen S‐Line Lab+; EKF diagnostics, Barleben, Germany). HRV was assessed for 24 h including the 8‐h intervention phase, and a home phase by means of a Holter electrocardiogram. All participants received the same standardized non‐relativised breakfast and lunch during the four trial visits. Results: Seventeen individuals (eight women, mean age 23.4 ± 3.3 years, body mass index 29.7 ± 3.8 kg/m2, glycated haemoglobin level 34.8 ± 3.1 mmol/mol [5.4 ± 0.3%], body fat 31.8 ± 8.2%) completed all four trial arms. Compared with SIT (89.4 ± 6.8 mg/dL), 8‐h mean glucose was lower in all other conditions (p < 0.05) and this was statistically significant compared with WALK (86.3 ± 5.2 mg/dL; p = 0.034). Two‐hour postprandial glucose after breakfast was approximately 7% lower for WALK compared with SIT (p = 0.002). Furthermore, significant time × condition effects on HRV parameters favouring light‐intensity walking were observed (p < 0.001). Conclusions: Replacement and interruption of prolonged sitting with light‐intensity walking showed a significant blood glucose‐lowering effect and improved HRV during an 8‐h work environment in young adults with overweight and obesity. [ABSTRACT FROM AUTHOR]

Affective temperaments are assumed to have biological and neural bases. In the present study, we analyzed 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images of healthy participants to explore the neural basis of affective temperaments. We utilized data of affective temperament measured by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire and 18F-FDG PET images of healthy participants from two of our previous studies. A multiple regression analysis was performed to assess the association between 18F-FDG uptake and temperament scores using Statistical Parametric Mapping 12. The final sample included 62 healthy participants. Whole-brain analysis revealed a cluster of 18F-FDG uptake that was significantly and positively associated with irritable temperament scores in the right cerebellum (Crus II, VIII, and IX). After further adjustment for the other four temperament scores, whole-brain analysis revealed a cluster of 18F-FDG uptake significantly and positively associated with irritable temperament scores in the left insula and right cerebellum (Crus II, VIII, and IX). However, no significant association was found between 18F-FDG uptake and the other four temperaments (depressive, cyclothymic, hyperthymic, and anxious). The left insula and right cerebellum of the cerebrocerebellar circuit may be one of the neural bases of irritable temperament. [ABSTRACT FROM AUTHOR]

Objective: Patients with Lewy body diseases have an increased risk of dementia, which is a significant predictor for survival. Posterior cortical hypometabolism on [18F]fluorodeoxyglucose positron emission tomography (PET) precedes the development of dementia by years. We therefore examined the prognostic value of cerebral glucose metabolism for survival. Methods: We enrolled patients diagnosed with Parkinson's disease (PD), Parkinson's disease with dementia, or dementia with Lewy bodies who underwent [18F]fluorodeoxyglucose PET. Regional cerebral metabolism of each patient was analyzed by determining the expression of the PD‐related cognitive pattern (Z‐score) and by visual PET rating. We analyzed the predictive value of PET for overall survival using Cox regression analyses (age‐ and sex‐corrected) and calculated prognostic indices for the best model. Results: Glucose metabolism was a significant predictor of survival in 259 included patients (n = 118 events; hazard ratio: 1.4 [1.2–1.6] per Z‐score; hazard ratio: 1.8 [1.5–2.2] per visual PET rating score; both p < 0.0001). Risk stratification with visual PET rating scores yielded a median survival of 4.8, 6.8, and 12.9 years for patients with severe, moderate, and mild posterior cortical hypometabolism (median survival not reached for normal cortical metabolism). Stratification into 5 groups based on the prognostic index revealed 10‐year survival rates of 94.1%, 78.3%, 34.7%, 0.0%, and 0.0%. Interpretation: Regional cerebral glucose metabolism is a significant predictor of survival in Lewy body diseases and may allow an earlier survival prediction than the clinical milestone "dementia." Thus, [18F]fluorodeoxyglucose PET may improve the basis for therapy decisions, especially for invasive therapeutic procedures like deep brain stimulation in Parkinson's disease. ANN NEUROL 2024;96:539–550 [ABSTRACT FROM AUTHOR]

This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes , Diabetes Care , and Diabetologia , which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single–time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal. [ABSTRACT FROM AUTHOR]

Objective: To examine cerebral functional alterations associated with sensory processing in patients with migraine and constant photophobia. Background: Migraine is a common headache disorder that presents with photophobia in many patients during attacks. Furthermore, some patients with migraine experience constant photophobia, even during headache‐free intervals, leading to a compromised quality of life. Methods: This prospective, case–control study included 40 patients with migraine (18 male and 22 female) who were recruited at an eye hospital and eye clinic. The patients were divided into two groups: migraine with photophobia group, consisting of 22 patients (10 male and 12 female) with constant photophobia, and migraine without photophobia group, consisting of 18 patients (eight male and 10 female) without constant photophobia. We used 18F‐fluorodeoxyglucose and positron emission tomography to compare cerebral glucose metabolism between the two patient groups and 42 healthy participants (16 men and 26 women). Results: Compared with the healthy group, both the migraine with photophobia and migraine without photophobia groups showed cerebral glucose hypermetabolism in the bilateral thalamus (p < 0.05, family‐wise error‐corrected). Moreover, the contrast of migraine with photophobia minus migraine without photophobia patients showed glucose hypermetabolism in the bilateral medial thalamus (p < 0.05, family‐wise error‐corrected). Conclusions: The medial thalamus may be associated with the development of continuous photophobia in patients with migraine. Plain Language Summary: Migraine attacks are often accompanied by photophobia, and some patients with migraine experience constant glare, even when they do not have a headache. We tried to understand if there are changes in the brains of patients with migraine with photophobia by comparing their brain scans to those of healthy participants. We found that the thalamus had more activity in patients with migraine who experience constant glare compared to patients with migraine who do not. [ABSTRACT FROM AUTHOR]

This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes , Diabetes Care , and Diabetologia , which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single–time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal. [ABSTRACT FROM AUTHOR]

The autoimmune destruction of β-cells in type-1 diabetes (T1D) is a multifactorial and poorly understood phenomenon. A major contribution to this autoimmune attack is the generation of autoantigens triggered by β-cell dysfunction. Under hypoxia, cells shift to anaerobic glycolysis, regulated by hypoxia-inducible factor (HIF)-1α. This adaptation ensures energy production through increased glycolytic flux and decreased oxidative phosphorylation. Dysregulation of glycolysis contributes to β-cell dysfunction in diabetes. HIF-1α activation in β-cells impacts both in vivo and in vitro insulin secretion and systemic glucose levels. HIF-1α also modulates immune cell phenotype, potentially influencing autoimmune destruction of β-cells. Although more studies are needed, prolyl-hydroxylase inhibitors, which stabilize HIF-1α, show promise as T1D therapeutics by protecting β-cells against cellular stress. Type 1 diabetes (T1D) is a common autoimmune disease in which dysregulated glucose metabolism is a key feature. T1D is both poorly understood and in need of improved therapeutics. Hypoxia is frequently encountered in multiple tissues in T1D patients including the pancreas and sites of diabetic complications. Hypoxia-inducible factor (HIF)-1, a ubiquitous master regulator of the adaptive response to hypoxia, promotes glucose metabolism through transcriptional and non-transcriptional mechanisms and alters disease progression in multiple preclinical T1D models. However, how HIF-1 activation in β-cells of the pancreas and immune cells (two key cell types in T1D) ultimately affects disease progression remains controversial. We discuss recent advances in our understanding of the role of hypoxia/HIF-1-induced glycolysis in T1D and explore the possible use of drugs targeting this pathway as potential new therapeutics. [ABSTRACT FROM AUTHOR]

Au@Pt nanozyme, a bimetallic core–shell structure Au and Pt nanoparticle, has attracted significant attention due to its excellent catalytic activity and stability. Here, we propose that Au@Pt improves glucose tolerance and reduces TG after four weeks administration. The transcriptomic analysis of mouse liver tissues treated with Au@Pt nanozyme showed changes in genes related to glucose and lipid metabolism signaling pathways, including glycolysis/gluconeogenesis, pyruvate metabolism, PPAR signaling, and insulin signaling. Moreover, analysis of fecal samples from mice treated with Au@Pt nanozyme showed significant changes in the abundance of beneficial gut microbiota such as Dubosiella, Parvibacter, Enterorhabdus, Monoglobus, Lachnospiraceae_UCG-008, Lachnospiraceae_UCG-006, Lachnospiraceae_UCG-001, and Christensenellaceae_R-7_group. Combined multi-omics correlation analyses revealed that the modulation of glucose and lipid metabolism by Au@Pt was strongly correlated with changes in hepatic gene expression profiles as well as changes in gut microbial profiles. Overall, our integrated multi-omics analysis demonstrated that Au@Pt nanozyme could modulate glucose and lipid metabolism by regulating the expression of key genes in the liver and altering the composition of gut microbiota, providing new insights into the potential applications of Au@Pt nanozyme in the treatment of metabolic disorder. [ABSTRACT FROM AUTHOR]

Background: Ectoine as an amino acid derivative is widely applied in many fields, such as the food industry, cosmetic manufacturing, biologics, and therapeutic agent. Large-scale production of ectoine is mainly restricted by the cost of fermentation substrates (e.g., carbon sources) and sterilization. Results: In this study, Halomonas cupida J9 was shown to be capable of synthesizing ectoine using xylose as the sole carbon source. A pathway was proposed in H. cupida J9 that synergistically utilizes both WBG xylose metabolism and EMP glucose metabolism for the synthesis of ectoine. Transcriptome analysis indicated that expression of ectoine biosynthesis module was enhanced under salt stress. Ectoine production by H. cupida J9 was enhanced by improving the expression of ectoine biosynthesis module, increasing the intracellular supply of the precursor oxaloacetate, and utilizing urea as the nitrogen source. The constructed J9U-P8EC achieved a record ectoine production of 4.12 g/L after 60 h of xylose fermentation. Finally, unsterile production of ectoine by J9U-P8EC from either a glucose-xylose mixture or corn straw hydrolysate was demonstrated, with an output of 8.55 g/L and 1.30 g/L of ectoine, respectively. Conclusions: This study created a promising H. cupida J9-based cell factory for low-cost production of ectoine. Our results highlight the potential of J9U-P8EC to utilize lignocellulose-rich agriculture waste for open production of ectoine. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM), prediabetes, and insulin resistance are highly prevalent in patients with ischemic stroke (IS). DM is associated with higher risk for poor outcomes after IS. Objective: Investigate the risk of recurrent vascular events and mortality associated with impaired glucose metabolism compared to normoglycemia in patients with IS and transient ischemic attack (TIA). Methods: Systematic literature search was performed in PubMed, Embase, Cochrane Library on 21st March 2024 and via citation searching. Studies that comprised IS or TIA patients and exposures of impaired glucose metabolism were eligible. Study Quality Assessment Tool was used for risk of bias assessment. Covariate adjusted outcomes were pooled using random-effects meta-analysis. Main outcomes: Recurrent stroke, cardiac events, cardiovascular and all-cause mortality and composite of vascular outcomes. Results: Of 10,974 identified studies 159 were eligible. 67% had low risk of bias. DM was associated with an increased risk for composite events (pooled HR (pHR) including 445,808 patients: 1.58, 95% CI 1.34–1.85, I2 = 88%), recurrent stroke (pHR including 1.161.527 patients: 1.42 (1.29–1.56, I2 = 92%), cardiac events (pHR including 443,863 patients: 1.55, 1.50–1.61, I2 = 0%), and all-cause mortality (pHR including 1.031.472 patients: 1.56, 1.34–1.82, I2 = 99%). Prediabetes was associated with an increased risk for composite events (pHR including 8,262 patients: 1.50, 1.15–1.96, I2 = 0%) and recurrent stroke (pHR including 10,429 patients: 1.50, 1.18–1.91, I2 = 0), however, not with mortality (pHR including 9,378 patients, 1.82, 0.73–4.57, I2 = 78%). Insulin resistance was associated with recurrent stroke (pHR including 21,363 patients: 1.56, 1.19–2.05, I2 = 55%), but not with mortality (pHR including 21,363 patients: 1.31, 0.66–2.59, I2 = 85%). Discussion: DM is associated with a 56% increased relative risk of death after IS and TIA. Risk estimates regarding recurrent events are similarly high between prediabetes and DM, indicating high cardiovascular risk burden already in precursor stages of DM. There was a high heterogeneity across most outcomes. [ABSTRACT FROM AUTHOR]

The mantle muscle of common cuttlefish, Sepia officinalis, is responsible both for high‐magnitude and rapid movements for locomotion, as well as sustained ventilation, which require specific metabolic, electrophysiological, and structural organization. Young cuttlefish have a highly oxidative phenotype and a rapid growth rate. Here, we show high rates of oxygen consumption and protein synthesis in juveniles, and these rates decay exponentially over the first few weeks of growth. This is associated with considerable citrate synthase activity (relative to larger cuttlefish) but a lack of glucose metabolism based on zero uptake of glucose by isolated muscle sheets and minimal activity of hexokinase (similar to larger animals). In contrast to glucose metabolism in the heart, glucose metabolism in these muscle sheets was not stimulated by extracellular taurine. Previous research revealed an unusual ion channel complement in mantle myocytes, the most notable feature of which is the lack of a Na+ current during depolarization. Because this adaptation is not consistent across the coleoid clade, we investigated excitation–contraction coupling. Here, mantle energetics and contractility, including the individual components of the total Ca2+ flux driving contraction, were studied. Results indicate that the majority of Ca2+ current underlying contractile stress development capacity in cuttlefish juveniles is not mediated by dihydropyridine‐sensitive L‐type channels, in contrast to their adult counterparts, and the sarcoplasmic reticulum contributes little to routine contractility. We had previously noted an influence of physiological levels of taurine in limiting cardiac contractility but found no analogous sensitivity in mantle muscle. Finally, transmission electron microscopy of subcellular architecture revealed the presence of sarcoplasmic tubular aggregates, suggesting that oxidative inhibition of sarcoplasmic reticulum function limits its role in this life stage. [ABSTRACT FROM AUTHOR]

Background: Abiotic stress seriously affects the growth and yield of crops. It is necessary to search and utilize novel abiotic stress resistant genes for 2.0 breeding programme in quinoa. In this study, the impact of drought stress on glucose metabolism were investigated through transcriptomic and metabolomic analyses in quinoa seeds. Candidate drought tolerance genes on glucose metabolism pathway were verified by qRT-PCR combined with yeast expression system. Results: From 70 quinoa germplasms, drought tolerant material M059 and drought sensitive material M024 were selected by comprehensive evaluation of drought resistance. 7042 differentially expressed genes (DEGs) were indentified through transcriptomic analyses. Gene Ontology (GO) analysis revealed that these DEGs were closely related to carbohydrate metabolic process, phosphorus-containing groups, and intracellular membrane-bounded organelles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis detected that DEGs were related to pathways involving carbohydrate metabolisms, glycolysis and gluconeogenesis. Twelve key differentially accumulated metabolites (DAMs), (D-galactose, UDP-glucose, succinate, inositol, D-galactose, D-fructose-6-phosphate, D-glucose-6-phosphate, D-glucose-1-phosphate, dihydroxyacetone phosphate, ribulose-5-phosphate, citric acid and L-malate), and ten key candidate DEGs (CqAGAL2, CqINV, CqFrK7, CqCELB, Cqbg1x, CqFBP, CqALDO, CqPGM, CqIDH3, and CqSDH) involved in drought response were identified. CqSDH, CqAGAL2, and Cqβ-GAL13 were candidate genes that have been validated in both transcriptomics and yeast expression screen system. Conclusion: These findings provide a foundation for elucidating the molecular regulatory mechanisms governing glucose metabolism in quinoa seeds under drought stress, providing insights for future research exploring responses to drought stress in quinoa. [ABSTRACT FROM AUTHOR]

Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle‐aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age‐related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3‐adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18‐month‐old) C57BL/6JN mice. Sustained β3‐AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a favorable adipokine profile. At the cellular level, CL treatment increased uncoupling protein 1 (UCP1)‐dependent thermogenesis in brown adipose tissue (BAT). However, in white adipose tissue (WAT) depots, CL treatment increased glycerol and lipid de novo lipogenesis (DNL) and turnover suggesting the activation of the futile substrate cycle of lipolysis and reesterification in a UCP1‐independent manner. Increased lipid turnover was also associated with the simultaneous upregulation of proteins involved in glycerol metabolism, fatty acid oxidation, and reesterification in WAT. Further, a dose‐dependent impact of CL treatment on inflammation was observed, particularly in subcutaneous WAT, suggesting a potential mismatch between fatty acid supply and oxidation. These findings indicate that chronic β3‐AR stimulation activates distinct cellular mechanisms that increase energy expenditure in BAT and WAT to improve systemic metabolism in aged mice. Considering that people lose BAT with aging, activation of futile lipid cycling in WAT presents a novel strategy for improving age‐related metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Background: Ubiquitin-specific protease 15 (USP15) exhibits amplifications in various tumors, including gastric cancer (GC), yet its biological function and mechanisms in GC progression remain elusive. Methods: Here, we established stable USP15 knockdown or overexpression GC cell lines and explored the potential mechanism of USP15 in GC. Besides, we also identified interacting targets of USP15. Results: USP15 knockdown significantly impeded cell proliferation, invasion, epithelial-mesenchymal transition, and distal colonization in xenograft models, while enhancing oxaliplatin's antitumor effect. USP15 was involved in ubiquitination modification of glycolytic regulators. Silencing of USP15 suppressed glycolytic activity and impaired mitochondrial functions. Interference with USP15 expression reversed tumor progression and distal colonization in vivo. HKDC1 and IGF2BP3 were found as core interacting targets of USP15, and HKDC1 was identified as a substrate for ubiquitination modification by USP15, whereby USP15 regulated glucose metabolism activity by inhibiting the ubiquitination degradation of HKDC1. Conclusions: Our study unveiled aberrantly high expression of USP15 in GC tissues, correlating with malignant progression and nonresponse to neoadjuvant therapy. USP15 inhibitors, if developed, could be effective in promoting chemotherapy through glucose metabolism remodeling. [ABSTRACT FROM AUTHOR]

Application of stable isotopically labelled (SIL) molecules in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) over a series of time points allows the temporal and spatial dynamics of biochemical reactions to be tracked in a biological system. However, these large kinetic MSI datasets and the inherent variability of biological replicates presents significant challenges to the rapid analysis of the data. In addition, manual annotation of downstream SIL metabolites involves human input to carefully analyse the data based on prior knowledge and personal expertise. To overcome these challenges to the analysis of spatiotemporal MALDI-MSI data and improve the efficiency of SIL metabolite identification, a bioinformatics pipeline has been developed and demonstrated by analysing normal bovine lens glucose metabolism as a model system. The pipeline consists of spatial alignment to mitigate the impact of sample variability and ensure spatial comparability of the temporal data, dimensionality reduction to rapidly map regional metabolic distinctions within the tissue, and metabolite annotation coupled with pathway enrichment modules to summarise and display the metabolic pathways induced by the treatment. This pipeline will be valuable for the spatial metabolomics community to analyse kinetic MALDI-MSI datasets, enabling rapid characterisation of spatio-temporal metabolic patterns from tissues of interest. [ABSTRACT FROM AUTHOR]

Cataracts are the world's leading cause of blindness, and diabetes is the second leading risk factor for cataracts after old age. Despite this, no preventative treatment exists for cataracts. The altered metabolism of excess glucose during hyperglycaemia is known to be the underlying cause of diabetic cataractogenesis, resulting in localised disruptions to fibre cell morphology and cell swelling in the outer cortex of the lens. In rat models of diabetic cataracts, this damage has been shown to result from osmotic stress and oxidative stress due to the accumulation of intracellular sorbitol, the depletion of NADPH which is used to regenerate glutathione, and the generation of fructose metabolites via the polyol pathway. However, differences in lens physiology and the metabolism of glucose in the lenses of different species have prevented the translation of successful treatments in animal models into effective treatments in humans. Here, we review the stresses that arise from hyperglycaemic glucose metabolism and link these to the regionally distinct metabolic and physiological adaptations in the lens that are vulnerable to these stressors, highlighting the evidence that chronic oxidative stress together with osmotic stress underlies the aetiology of human diabetic cortical cataracts. With this information, we also highlight fundamental gaps in the knowledge that could help to inform new avenues of research if effective anti-diabetic cataract therapies are to be developed in the future. [ABSTRACT FROM AUTHOR]

High-Protein Mulberry is a novel strain of mulberry. High-Protein Mulberry leaves (HPM) were the subject of this study, which aimed to investigate its efficacy and underlying mechanisms in modulating glucose and lipid metabolism. A six-week intervention using db/db mice was carried out to assess the effects of HPM on serum lipid levels, liver function, and insulin (INS) levels. qRT-PCR and Western Blotting were employed to measure key RNA and protein expressions in the PI3K/Akt and PPARα/CPT-1 pathways. UHPLC-MS and the Kjeldahl method were utilized to analyze the component content and total protein. Additionally, network pharmacology was employed to predict regulatory mechanism differences between HPM and Traditional Mulberry leaves. The results of the study revealed significant improvements in fasting blood glucose, glucose tolerance, and insulin resistance in mice treated with HPM. HPM notably reduced serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and INS, while increasing high-density lipoprotein cholesterol (HDL-C) levels. The treatment also effectively mitigated liver fatty lesions, inflammatory infiltration, and islet atrophy. HPM activation of the PI3K/Akt/PPARα/CPT-1 pathway suggested its pivotal role in the regulation of glucose and lipid metabolism. With its rich composition and pharmacodynamic material basis, HPM displayed a greater number of targets associated with glucose and lipid metabolism pathways, underscoring the need for further research into its potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Giardia lamblia, the cause of giardiasis, significantly impacts patients with metabolic disorders related to insulin resistance (IR). Both giardiasis and metabolic disorders share elements such as chronic inflammation and intestinal dysbiosis, which substantially affect the metabolic and cytokine profiles of patients. This review discusses the mechanisms of virulence of G. lamblia, its influence on the immune system, and its association with metabolic disorders. The review aims to show how G. lamblia invasion acts on the immune system and the glucose and lipid metabolism. Key findings reveal that G. lamblia infection, by disrupting intestinal permeability, alters microbiota composition and immune responses, potentially impairing metabolic status. Future research should focus on elucidating the specific mechanisms by which G. lamblia influences the metabolism, exploring the long-term consequences of chronic infection, and developing targeted therapeutic strategies that include both parasitic and metabolic aspects. These insights underscore the need for a multidisciplinary approach to the treatment of giardiasis in patients with metabolic disorders. [ABSTRACT FROM AUTHOR]

Women typically have less muscle mass and more fat mass than men, while at the same time possessing similar or even greater whole‐body insulin sensitivity. Our study aimed to investigate the molecular factors in primarily adipose tissue, but also in skeletal muscle, contributing to this sex difference. In healthy, moderately active premenopausal women and men with normal weight (28 ± 5 and 23 ± 3 years old; BMI 22.2 ± 1.9 and 23.7 ± 1.7) and in healthy, recreationally active women and men with overweight (32.2 ± 6 and 31.0 ± 5 years old; BMI 29.8 ± 4.3 & 30.9 ± 3.7) matched at age, BMI, and fitness level, we assessed insulin sensitivity and glucose tolerance with a hyperinsulinemic–euglycemic clamp or oral glucose tolerance test and studied subcutaneous adipose tissue and skeletal muscle samples with western blotting. Additionally, we traced glucose‐stimulated glucose disposal in adipose tissues of female and male C57BL/6J littermate mice aged 16 weeks and measured glucose metabolic proteins. Our findings revealed greater protein expression related to glucose disposal in the subcutaneous adipose tissue (AKT2, insulin receptor, glucose transport 4) and skeletal muscle (hexokinase II, pyruvate dehydrogenase) in women compared to matched men with normal weight and with overweight. This increased protein capacity for glucose uptake extended to white adipose tissues of mice accompanied with ~2‐fold greater glucose uptake compared to male mice. Furthermore, even in the obese state, women displayed better glucose tolerance than matched men, despite having 46% body fat and 20 kg less lean mass. In conclusion, our findings suggest that the superior potential for glucose disposal in female subcutaneous adipose tissue and skeletal muscle, driven by greater expression of various glucose metabolic proteins, compensates for their lower muscle mass. This likely explains women's superior glucose tolerance and tissue insulin sensitivity compared to men. [ABSTRACT FROM AUTHOR]

Because of the advent of genome-editing technology, gene knockout (KO) hamsters have become attractive research models for diverse diseases in humans. This study established a new KO model of diabetes by disrupting the insulin receptor substrate-2 (Irs2) gene in the golden (Syrian) hamster. Homozygous KO animals were born alive but with delayed postnatal growth until adulthood. They showed hyperglycemia, high HbA1c, and impaired glucose tolerance. However, they normally responded to insulin stimulation, unlike Irs2 KO mice, an obese type 2 diabetes (T2D) model. Consistent with this, Irs2 KO hamsters did not increase serum insulin levels upon glucose administration and showed β-cell hypoplasia in their pancreas. Thus, our Irs2 KO hamster provide a unique T2D animal model that is distinct from the obese T2D models. This model may contribute to a better understanding of the pathophysiology of human non-obese T2D with β-cell dysfunction, the most common type of T2D in East Asian countries, including Japan. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions To assess oxytocin's acute glucoregulatory impact in men with type 2 diabetes in the context of our previous findings that oxytocin improves β‐cell responsivity in healthy men.In a double‐blind, crossover comparison, intranasal oxytocin (24 IU) and placebo, respectively, were administered to 25 fasted men with non‐insulin–treated type 2 diabetes (age ± standard error of the mean, 63.40 ± 1.36 years; body mass index, 27.77 ± 0.66 kg/m2; HbA1c, 6.86% ± 0.08%; Homeostatic Model Assessment of Insulin Resistance (HOMA‐IR, 3.44 ± 0.39) 60 minutes before an oral glucose tolerance test (oGTT). Key outcomes were compared with previous results in men with normal weight or obesity.Oxytocin compared with placebo increased plasma oxytocin concentrations and reduced the heart rate, but did not alter glucose metabolism in the 3 hours after oGTT onset (area under the curve, glucose, 2240 ± 80.5 vs. 2190 ± 69.5 mmol/L × min; insulin, 45 663 ± 4538 vs. 44 343 ± 4269 pmol/L × min; C‐peptide, 235 ± 5.1 vs. 231 ± 15.9 nmol/L × min).This outcome contrasts with the oxytocin‐induced attenuation of early postprandial glucose excursions in normal‐weight individuals, but is in line with the absence of respective effects in men with obesity. We conclude that insulin resistance in type 2 diabetes is associated with decreased sensitivity to the acute glucoregulatory effect of oxytocin in male individuals. [ABSTRACT FROM AUTHOR]

The central nervous system regulates feeding, weight and glucose homeostasis in rodents and humans, but the site-specific mechanisms remain unclear. The dorsal vagal complex in the brainstem that contains the nucleus of the solitary tract (NTS) and area postrema (AP) emerges as a regulatory center that impacts energy and glucose balance by monitoring hormonal and nutrient changes. However, the specific mechanistic metabolic roles of the NTS and AP remain elusive. This mini-review highlights methods to study their distinct roles and recent findings on their metabolic differences and similarities of growth differentiation factor 15 (GDF15) action and glucose sensing in the NTS and AP. In summary, future research aims to characterize hormonal and glucose sensing mechanisms in the AP and/or NTS carries potential to unveil novel targets that lower weight and glucose levels in obesity and diabetes. [ABSTRACT FROM AUTHOR]

To investigate the effects of Pseudomonas monteilii SX001 on various parameters of cucumber plants under salt stress, the salt-sensitive cucumber variety "Jinyou No. 4" was used as the test material, and coconut bran was used to simulate salt stress by applying NaCl solution. The results indicated that salt stress significantly reduced the morphological structure, relative growth rate, root morphology, and photosynthetic parameters of the cucumber plants. Leaf starch, soluble sugar, and sucrose contents significantly increased, whereas their levels in roots decreased. Cell membrane damage leads to the accumulation of reactive oxygen species and malondialdehyde, with notable increases in the activities of major antioxidant enzymes such as SOD, CAT, and POD. Nitrogen metabolism was disrupted, as evidenced by a significant decrease in nitrate nitrogen content and an increase in ammonium nitrogen content, as well as a significant reduction in the activity of NR enzymes involved in nitrogen metabolism. The enzyme activity in the cucumber rhizosphere soil decreased. However, Pseudomonas monteilii SX001 significantly enhanced the growth of cucumber seedlings under salt stress, improved photosynthetic efficiency, and facilitated sugar transformation and transport via glucose metabolism. Additionally, Pseudomonas monteilii SX001 reduced the reactive oxygen content and increased antioxidant enzyme activity. It also increased the activity of substrate enzymes and decreased the diversity of rhizosphere soil microorganisms but also increased the abundance of Asticcacaulis, Acinetobacter, Brevundimonas, Pseudomonas, and Enterobacter. These findings demonstrate that Pseudomonas monteilii SX001 is a promising bioinoculant for alleviating salt stress in cucumber production and improving soil health. [ABSTRACT FROM AUTHOR]

Introduction: Human chemerin is an adipokine that regulates chemotaxis, inflammation, and glucose metabolism. In addition, accumulating evidence suggests that chemerin promotes apoptosis, autophagy, and pyroptosis. However, there are no data on its impact on eryptosis. The current study aimed to analyze the effects of human active Glu-Ser chemerin on eryptosis in vitro. Materials and Methods: Human chemerin 0-2-10-50 µg/mL was incubated for 24 h with human erythrocytes (hematocrit 0.4%) obtained from eight healthy individuals. Flow cytometry-based determination of phospholipid scrambling, reactive oxygen species (ROS) production, and intracellular Ca levels was performed. To supplement data on ROS and Ca signaling in chemerin-mediated eryptosis, incubation in the presence or absence of antioxidants vitamin C and N-acetylcysteine and Ca-binding agent EGTA was carried out, respectively. Confocal microscopy-based techniques were used to detect reactive nitrogen species (RNS) generation, involvement of caspase-3 and caspase-8, as well as the state of lipid order in cell membranes of erythrocytes exposed to human Glu-Ser chemerin. Results: Our observations suggest that human Glu-Ser chemerin had no impact on eryptosis parameters at 2 µg/mL. However, chemerin stimulated phosphatidylserine externalization, ROS production, and Ca accumulation at higher concentrations suggesting activation of eryptosis. Ca uptake turned out to be at least partly required for chemerin-mediated eryptosis. Chemerin-mediated erythrotoxicity was additionally mediated by RNS, caspase-3, and caspase-8. Moreover, Glu-Ser chemerin promoted reduction in the liquid-ordered phase of cell membranes in erythrocytes. Conclusions: The present study first discloses that human chemerin can induce eryptosis via Ca-dependent mechanisms at concentrations noticeably exceeding circulating levels. Thus, chemerin-induced eryptosis can hardly contribute to eryptosis-mediated anemia in diseases associated with enhanced levels of chemerin in blood. [ABSTRACT FROM AUTHOR]

Filamentous algae have potential application to wastewater treatment, in particular for efficient recovery of nutrients into biomass. However, supplying inorganic carbon is a major limiting factor. The utilisation of organic carbon present in wastewater may reduce the constraints in carbon supply, however there is little knowledge of mixotrophic growth amongst filamentous algae. This study investigated the utilisation of organic carbon sources relevant to wastewater by the filamentous xanthophyte alga Tribonema. Algae growth was compared in the absence of organic carbon (autotrophic) and in presence of 0.2 g-C L-1 glucose, ethanol or acetate under mixotrophic (presence of organic carbon and light) or heterotrophic (presence of organic carbon and absence of light) conditions. To investigate direct utilisation of organic carbon and indirect utilisation via bacterial CO2-genesis, cultivation was performed under both axenic and non-axenic conditions. Tribonema was found to directly utilise glucose, which increased mixotrophic productivity and maintained growth under heterotrophic conditions. In contrast, acetate was only indirectly utilised mixotrophically in the presence of bacteria, whereas ethanol was not utilised under any conditions. The underlying mechanisms of glucose utilisation by Tribonema were also investigated by analysing its photosynthetic rate and respiration rate under glucose concentrations ranging from 0 – 100 g L-1. Based on the results, enhancements to metabolic pathways and reduced CO2 requirements provided by glucose utilisation were proposed. Despite the positive results with respect to glucose utilisation, out competition for this resource by bacteria suggest that Tribonema is more suitable for treatment of wastewater with low organic carbon concentrations, such as secondary-treated wastewater effluent. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is the predominant metabolic epidemic posing a major threat to global health. Growing evidence indicates that gut microbiota (GM) may critically influence the progression from normal glucose tolerance, to pre-diabetes, to T2D. On the other hand, regular exercise contributes to the prevention and/or treatment of the disease, and evidence suggests that a possible way regular exercise favorably affects T2D is by altering GM composition toward health-promoting bacteria. However, research regarding this potential effect of exercise-induced changes of GM on T2D and the associated mechanisms through which these effects are accomplished is limited. This review presents current data regarding the association of GM composition and T2D and the possible critical GM differentiation in the progression from normal glucose, to pre-diabetes, to T2D. Additionally, potential mechanisms through which GM may affect T2D are presented. The effect of exercise on GM composition and function on T2D progression is also discussed. [ABSTRACT FROM AUTHOR]

Prior studies have extensively investigated the essential oil derived from the Mediterranean cypress, Cupressus sempervirens. However, the 'Stricta' variety, known for its ornamental value, has received less attention in terms of its oil composition and potential health benefits. The objective of this research was to comprehensively analyze the chemical components and medicinal properties of the essential oil extracted from C. sempervirens 'Stricta' (CSSLEO) grown in Egypt. Utilizing gas chromatography–mass spectrometry (GC–MS), the investigation identified 22 compounds within CSSLEO, with α-pinene and δ-3-carene being predominant, accounting for 96.01% of the oil. In vitro assays evaluated CSSLEO's cytotoxic effects on cancer cell lines, revealing notable anticancer potential. Additionally, the oil displayed antidiabetic properties by impeding crucial enzymes involved in glucose metabolism. Complementary in silico network pharmacology and molecular docking studies provided insights into the possible interactions between CSSLEO's key compounds and essential proteins and pathways in cancer treatment. The results underscored CSSLEO's intricate composition and its promising applications in cancer prevention and diabetes management. The conclusions drawn from this research underscore the need for further investigation to validate CSSLEO's clinical effectiveness and to gain a deeper understanding of its therapeutic mechanisms, with a view to harnessing its potential in oncology and endocrinology. [ABSTRACT FROM AUTHOR]

Objective: This study utilized a data-driven Bayesian model to automatically identify distinct latent disease factors represented by overlapping glucose metabolism patterns from 18F-Fluorodeoxyglucose PET (18F-FDG PET) to analyze heterogeneity among patients with TLE. Methods: We employed unsupervised machine learning to estimate latent disease factors from 18F-FDG PET scans, representing whole-brain glucose metabolism patterns in seventy patients with TLE. We estimated the extent to which multiple distinct factors were expressed within each participant and analyzed their relevance to epilepsy burden, including seizure onset, duration, and frequency. Additionally, we established a predictive model for clinical prognosis and decision-making. Results: We identified three latent disease factors: hypometabolism in the unilateral temporal lobe and hippocampus (factor 1), hypometabolism in bilateral prefrontal lobes (factor 2), and hypometabolism in bilateral temporal lobes (factor 3), variably co-expressed within each patient. Factor 3 demonstrated the strongest negative correlation with the age of onset and duration (r = − 0.33, − 0.38 respectively, P < 0.05). The supervised classifier, trained on latent disease factors for predicting patient-specific antiepileptic drug (AED) responses, achieved an area under the curve (AUC) of 0.655. For post-surgical seizure outcomes, the AUC was 0.857, and for clinical decision-making, it was 0.965. Conclusions: Decomposing 18F-FDG PET-based phenotypic heterogeneity facilitates individual-level predictions relevant to disease monitoring and personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]

M1/M2 macrophage polarization plays an important role in regulating the balance of the microenvironment within tissues. Moreover, macrophage polarization involves the reprogramming of metabolism, such as glucose and lipid metabolism. Transcriptional coactivator B‐cell lymphoma‐3 (Bcl‐3) is an atypical member of the IκB family that controls inflammatory factor levels in macrophages by regulating nuclear factor kappa B pathway activation. However, the relationship between Bcl‐3 and macrophage polarization and metabolism remains unclear. In this study, we show that the knockdown of Bcl‐3 in macrophages can regulate glycolysis‐related gene expression by promoting the activation of the nuclear factor kappa B pathway. Furthermore, the loss of Bcl‐3 was able to promote the interferon gamma/lipopolysaccharide‐induced M1 macrophage polarization by accelerating glycolysis. Taken together, these results suggest that Bcl‐3 may be a candidate gene for regulating M1 polarization in macrophages. [ABSTRACT FROM AUTHOR]

Objective: Half of ALS patients are cognitively and/or behaviourally impaired. As cognition/behaviour and cerebral glucose metabolism can be correlated by means of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET), we aimed to utilise FDG-PET, first, to replicate group-level differences in glucose metabolism between non-demented ALS patients separated into non-impaired (ALSni), cognitively impaired (ALSci), behaviourally impaired (ALSbi), and cognitively and behaviourally impaired (ALScbi) groups; second, to investigate glucose metabolism and performance in various cognitive domains; and third, to examine the impact of partial volume effects correction (PVEC) of the FDG-PET data on the results. Methods: We analysed neuropsychological, clinical, and imaging data from 67 ALS patients (30 ALSni, 21 ALSci, 5 ALSbi, and 11 ALScbi). Cognition was assessed with the Edinburgh Cognitive and Behavioural ALS Screen, and two social cognition tests. FDG-PET and structural MRI scans were acquired for each patient. Voxel-based statistical analyses were undertaken on grey matter volume (GMV) and non-corrected vs. PVE-corrected FDG-PET scans. Results: ALSci and ALScbi had lower cognitive scores than ALSni. In contrast to both ALSni and ALSci, ALScbi showed widespread hypometabolism in the superior- and middle-frontal gyri in addition to the right temporal pole. Correlations were observed between the GMV, the FDG-PET signal, and various cognitive scores. The FDG-PET results were largely unaffected by PVEC. Interpretation: Our study identified widespread differences in hypometabolism in the ALScbi-ni but not in the ALSci-ni group comparison, raising the possibility that cerebral metabolism may be more closely related to the presence of behavioural changes than to mild cognitive deficits. [ABSTRACT FROM AUTHOR]

Background: Cancer-derived exosomes facilitate chemoresistance by transferring RNAs, yet their role in exosomal microRNA-221-3p (miR-221-3p) regulation of adriamycin resistance in breast cancer (BC) remains unclear. Methods: Adriamycin-resistant BC cells were developed from MCF-7 and MDA-MB-231 cells by incremental adriamycin exposure. The miR-221-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction. Subsequently, exosomes were isolated and incubated with BC cells, and exosome-mediated adriamycin sensitivity was evaluated using Cell Counting Kit-8, colony formation, and flow cytometry assays. Sensitive cells were cocultured with miR-221-3p inhibitor-treated cells to assess adriamycin resistance. Moreover, the interaction between miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was validated using a dual luciferase reporter gene assay. Mimics and inhibitors were used to determine the effects of miR-221-3p on adriamycin resistance. Results: Elevated levels of miR-221-3p expression were observed in adriamycin-resistant BC cells and exosomes. Sensitive cells were cocultured with exosomes from resistant cells, resulting in increased half-maximal inhibitory concentration value and proliferation, and reduced adriamycin-induced apoptosis. However, the effects of coculturing sensitive cells with adriamycin-resistant cells were significantly weakened by miR-221-3p inhibitor transfection in adriamycin-resistant cells. PIK3R1 was found to be a target of miR-221-3p, and miR-221-3p mimics enhanced adriamycin resistance in sensitive cells. miR-221-3p inhibitors increased the expression of PIK3R1, p-AKT, c-Myc, HK2, and PKM2, decreased FOXO3 expression, and weakened the adriamycin resistance in resistant cells. Conclusions: miR-221-3p can be transferred between BC cells through exosomes. High levels of miR-221-3p were found to target PIK3R1 and promoted adriamycin resistance in BC cells. [ABSTRACT FROM AUTHOR]

Globally, type 2 diabetes mellitus (T2DM) is a major threat to the public's health, particularly in low- and middle-income countries (LMICs). The production of short-chain fatty acids (SCFAs) by the gut microbiota has been reported to have the potential to reduce the prevalence of T2DM, particularly in LMICs where the disease is becoming more common. Dietary fibers are the primary source of SCFAs; they can be categorized as soluble (such as pectin and inulin) or insoluble (such as resistant starches). Increased consumption of processed carbohydrates, in conjunction with insufficient consumption of dietary fiber, has been identified as a significant risk factor for type 2 diabetes (T2DM). However, there are still controversies over the therapeutic advantages of SCFAs on human glucose homeostasis, due to a lack of studies in this area. Hence, a few questions need to be addressed to gain a better understanding of the beneficial link between SCFAs and glucose metabolism. These include the following: What are the biochemistry and biosynthesis of SCFAs? What role do SCFAs play in the pathology of T2DM? What is the most cost-effective strategy that can be employed by LMICs with limited laboratory resources to enhance their understanding of the beneficial function of SCFAs in patients with T2DM? To address the aforementioned questions, this paper aims to review the existing literature on the protective roles that SCFAs have in patients with T2DM. This paper further discusses possible cost-effective and accurate strategies to quantify SCFAs, which may be recommended for implementation by LMICs as preventive measures to lower the risk of T2DM. [ABSTRACT FROM AUTHOR]

The growing incidence of diabetes mellitus (DM) and depression is a global public health issue. Alpiniae oxyphyllae Fructus (AOF) is a kind of medicinal and edible plant which be found with anti-diabetic property, and could improve depression-like symptoms. This study aimed to screen active targets and potential mechanisms of AOF in treating DM with depression. Injection of streptozotocin (STZ) and exposure to chronic unpredictable mild stress (CUMS) for 4 weeks were used to conduct the DM with depression mice model. Behavioral tests, indexes of glucose metabolism, monoamine neurotransmitters, inflammatory cytokine and oxidative stress were measured. Histopathological change of hippocampus tissue was observing by HE and Nissl staining. UPLC-Q-Exactive Orbitrap/MS, network pharmacology and molecular docking were used to explore the chemical components and mechanisms of AOF on the DM with depression. AOF showed a reversed effect on body weight in DM with depression mice. Glucose metabolism and insulin resistance could be improved by treatment of AOF. In addition, AOF could alleviate depression-like behaviors based on the results of behavior tests and monoamine neurotransmitters. AOF also attenuated STZ-CUMS induced neuron injury in hippocampus. Next, a total of 61 chemical components were identified in the UPLC-Q-Exactive Orbitrap/MS analysis of the extract of AOF. Network pharmacology analysis suggested that 12 active components and 227 targets were screened from AOF, and 1802 target genes were screened from DM with depression, finally 126 intersection target genes were obtained. Drug-disease targets network was constructed and implied that the top five components with a higher degree value includes quercetin, nootkatone, baicalein, (-)-epicatechin and nootkatol. Protein-protein interaction (PPI) network showed that MAPK1, FOS, AKT1, IL6 and TP53 may be the core intersection targets. The mechanism of the effect of AOF on DM with depression was analyzed through gene ontology (GO), and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, mainly involved in AGE/RAGE, PI3K/AKT, and MAPK signaling pathways. The results of molecular docking indicated that quercetin, nootkatone, baicalein, (-)-epicatechin and nootkatol all had good binding to the core intersection targets. Overall, our experimental researches have demonstrated that AOF could exert the dual effects of anti-diabetic and anti-depression on DM with depression mice, through multi-targets and multi-pathways. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is characterized by the dysregulation of glucose homeostasis, resulting in hyperglycemia. However, concerns have been raised about the safety and efficacy of current hypoglycemic drugs due to undesirable side effects. Increasing studies have shown that whole grains (WG) consumption is inversely associated with the risk of T2DM and its subsequent complications. Thus, dietary strategies involving functional components from the WG provide an intriguing approach to restoring and maintaining glucose homeostasis. This review provides a comprehensive understanding of the major functional components derived from WG and their positive effects on glucose homeostasis, demonstrates the underlying molecular mechanisms targeting hepatic glucose metabolism, and discusses the unclear aspects according to the latest viewpoints and current research. Improved glycemic response and insulin resistance were observed after consumption of WG-derived bioactive ingredients, which are involved in the integrated, multi-factorial, multi-targeted regulation of hepatic glucose metabolism. Promotion of glucose uptake, glycolysis, and glycogen synthesis pathways, while inhibition of gluconeogenesis, contributes to amelioration of abnormal hepatic glucose metabolism and insulin resistance by bioactive components. Hence, the development of WG-based functional food ingredients with potent hypoglycemic properties is necessary to manage insulin resistance and T2DM. [ABSTRACT FROM AUTHOR]

Summary: This study investigated the impact of comprehensive sleep patterns on glycaemic parameters and endothelial function in adolescents and young adults with type 1 diabetes (T1D). Thirty subjects with type 1 diabetes (aged 13–25) without chronic complications participated. For 1 week, glucose levels were monitored by real‐time continuous glucose monitoring (CGM) and sleep was simultaneously assessed by actigraphy. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Flow‐mediated dilatation (FMD) measured endothelial function at the brachial artery. Insulin sensitivity was determined by calculated estimated glucose disposal rate (eGDR). Glycaemic control was assessed using haemoglobin A1C (HbA1C) levels. To address potential confounding by metabolic syndrome on the FMD results, three affected subjects were excluded from FMD correlation analyses. Participants with PSQI scores >5 had a lower %FMD compared with those with scores ≤5 (4.6 ± 3.7% vs. 7.6 ± 3.0%, p = 0.03). Multivariate analysis indicated that lower sleep efficiency and higher sleep duration variability were associated with higher HbA1C levels (β = −0.076, 95%CI [−0.145, −0.008], p = 0.029; β = 0.012, 95%CI [0.001, 0.023], p = 0.033). Irregular sleep timing and lower sleep efficiency were related to decreased insulin sensitivity (sleep midpoint irregularity β = −1.581, 95%CI [−2.661, −0.502], p = 0.004, and sleep efficiency β = 0.147, 95%CI [0.060, 0.235], p = 0.001). No significant associations were found between glycaemic parameters and FMD. Our study demonstrated that sleep irregularity in type 1 diabetes was associated with glycaemic control and insulin resistance, while poor subjective sleep quality was linked to endothelial dysfunction. Promoting healthy sleep habits, including consistent sleep timing could benefit metabolic and cardiovascular health in type 1 diabetes. [ABSTRACT FROM AUTHOR]