Search Results (285)

This research investigated the impact of corn–soybean meal-based fermented feed on the growth performance, pork quality, and fatty acid profiles of lean-type finishing pigs. A total of 80 lean-type growing DLY (Duroc × Landrace–Yorkshire) pigs were randomly assigned to 2 groups, with 5 replicates of 8 pigs per pen. The pigs in control group (CON group) were fed a basal diet, while the pigs in fermented feed group (FF group) were fed a diet supplemented with 10% fermented feed. The experimental period lasted 70 days. Results exhibited that pigs in FF group had a significant increase in final body weight and average daily gain (ADG) (p < 0.05) and had a significant decrease in the feed-to-gain ratio (F/G) (p < 0.05). The FF group also exhibited significant promotion in muscle intramuscular fat content, marbling score, and meat color and significantly reduced the meat shear force and drip loss (p < 0.05). Serum analysis indicated that fermented feed significantly elevated blood glucose, total cholesterol, triglyceride levels, and serum hormones such as insulin, leptin, and IGF-1 (p < 0.05). Additionally, fermented feed significantly elevated the levels of polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs), whereas it decreased the saturated fatty acids (SFAs) contents (p < 0.05). The fermented feed also significantly enhanced pork nutritional values (p < 0.05). The fermented feed increased the expression of IGF-1, SREBP1c, PDE3, PPARγ, SCD5, and FAT/CD36 mRNA (p < 0.05). Furthermore, microbial 16S rDNA analysis uncovered that FF supplementation significantly reduced the Campilobacterota phylum abundance, while increasing the genus abundances of Clostridium_sensu_stricto, norank_f_Oscillospiraceae, unclassified_c_Clostridia, and V9D2013 (p < 0.05). In summary, the results indicated that the microbial fermented feed exhibited the regulation effects on pork quality and nutritional values of lean-type pigs through regulating lipid metabolism and gut microbial composition. Full article

Background: Obesity is associated with insulin resistance (IR) and characterized by impaired activation of the PI3K/AKT route and glucose uptake. Elevated plasma levels of palmitic acid (PA) diminish insulin signaling in vitro and in vivo. Origanum vulgare L. essential oil (OVEO) is rich in monoterpenes with protective effects against IR. Objective: The study aimed to assess total phenols content and antioxidant activity of OVEO and its cytotoxicity, as well as its effect on insulin signaling and glucose uptake in PA-treated adipocytes. Methods: The quantification of total phenolic content was determined using the Folin–Ciocalteu method, while the antioxidant capacity of OVEO was assessed by DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) methods. The cytotoxicity of OVEO (0.1–10 µg/mL) was assessed using the MTS assay. SW872 adipocytes were incubated with 0.4 mM PA for 24 h, with or without a 2 h preincubation of OVEO, and then stimulated with insulin (100 nM, 10 min) or a vehicle. Phosphorylation of Tyr-IRS-1, Ser-AKT, and Thr-AS160 was analyzed by Western blot, and glucose uptake was measured using 2-NBDG. Results: OVEO contained phenols and exhibits antioxidant capacity. All the concentrations of OVEO assessed were not cytotoxic on SW872 adipocytes. PA decreased basal phospho-AS160 as well as insulin-stimulated phospho-IRS1, phospho-AKT, phospho-AS160 and glucose uptake, while OVEO co-treatment enhanced these markers. Conclusions: These findings suggest a beneficial effect of OVEO on the PA-impaired insulin pathway and glucose uptake, which might be explained by its phenolic content and antioxidant capacity, highlighting its potential as a complementary therapeutic agent for IR and related metabolic disorders. Full article

Background/Objectives: We evaluated the efficacy of a good lifestyle intervention on the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children with Down syndrome (DS). Methods: This retrospective longitudinal study included 31 children with Down syndrome (DS) who were affected by MASLD and attended nutritional counseling based on a nutritional approach (e.g., Mediterranean diet and antioxidant supplements), as well as physical exercise. Clinical parameters, markers of low-grade systemic inflammation, and hepatic steatosis, as assessed by ultrasound, were evaluated at baseline (T0) and after 6 months (T1). Results: Several anthropometric and biochemical parameters, including body mass index, waist circumference, diastolic and systolic blood pressure, aspartate aminotransferase, basal insulin, insulin resistance, pro-inflammatory interleukin-1β, and anti-inflammatory interleukin-10, showed significant improvement after 6 months of a nutritional approach. This study also found a regression of at least one grade of hepatic steatosis in a significant portion of patients, especially in those who received antioxidant supplements. Conclusions: Our study further supports the hypothesis that a healthy lifestyle intervention, based on adherence to the Mediterranean diet, natural supplements with antioxidant properties, and regular physical activity, can be considered a safe therapeutic approach for reducing the risk and severity of MASLD in children with DS. Full article

The gastrointestinal (GI) tract is under neural, endocrine and paracrine control. The release (basal and in the presence of either cholinergic and opioid antagonists) of Met-enkephalin, insulin-like growth factor 1 (IGF-1) and somatostatin (SRIF) was determined quantitatively in vitro using explants of the crop, proventriculus and duodenum from either day 0 or day 1 chicks. In addition, the effects of cholinergic and opioid antagonists on PENK gene expression were examined. Thus, the aim of this study was to determine the roles of cholinergic and opioid receptors in the GI tract in newly hatched chickens. Moreover, the effect of IGF-1 and Met-enkephalin on cell division in duodenal explants in vitro was determined. There was both the release of Met-enkephalin from, and PENK expression in, the explants of the crop, proventriculus and duodenum tissue. This is the first report of any neuropeptide(s) being synthesized in and/or released from the crop. In vitro release of Met-enkephalin, IGF-1 and SRIF from duodenal and proventriculus explants was influenced (p < 0.01) by either cholinergic or opioid antagonists; for instance, in the presence of atropine, decreases (p < 0.001) of 17.8% and 57.7% are seen, respectively, in Met-enkephalin release and PENK expression in crop explants from day 1 chicks. Moreover, in the presence of atropine, there were increases (p < 0.001) of 47.7% and 70.9% in IGF-1 release in proventriculus explants from, respectively, day 0 and day 1 chicks. Met-enkephalin and/or IGF-1 stimulated the cell division of duodenal explants in vitro. This is the first report of Met-enkephalin release and PENK expression in the avian crop and of the effects of cholinergic or opioid antagonists on these factors. It is also the first report of either cholinergic or opioid control of IGF-1 release in the periphery of any species. There were strong relationships (p < 0.05) between the release of Met-enkephalin and that of IGF-1 in the duodenum and between the release of SRIF and that of IGF-1 in the proventriculus. This is the first report of IGF-1 and Met-enkephalin stimulating (p < 0.001) the proliferation of duodenal cells and, together, exerting a synergist effect. It is concluded that the release of Met-enkephalin, IGF-1 and SRIF from foregut regions is under tonic cholinergic and opioid control. Full article

Background and Clinical Significance: Pituitary apoplexy is an extremely rare condition in children and adolescents with a rapid onset due to acute hemorrhage, infarction, or both in the pituitary gland. Most frequently, pituitary apoplexy is an asymptomatic or subclinical entity. Few cases of pituitary apoplexy with concurrent SARS-CoV-2 infection or COVID-19 vaccination have been reported. Case Presentation: We present the case of a 13-year-8-month-old boy who presented in our pediatric endocrinology department for the evaluation of short stature. He was previously diagnosed with secondary hypothyroidism and was treated with levothyroxine. At admission, clinical examination revealed a height of 141 cm (−2.68 SD/−2.4 SD corrected for mid-parental height), normal weight (60th centile), Tanner-stage G2P1, and delayed bone age. Basal IGF1 was normal, but the tests performed to assess the GH reserve confirmed the GH deficiency (peak GH value 3.11 ng/mL after clonidine/0.95 ng/mL after insulin). The brain MRI revealed a subacute pituitary hemorrhage. Thrombophilia and coagulopathies were excluded by further testing. Anti-SARS-CoV-2 (anti-S-protein IgG) antibodies (>200 BAU/mL) were compatible with COVID-19 infection, indicating a possible association between these two entities. At 3-month follow-up, physical examination showed a 3 cm height gain and advancing pubertal development (G4P2). Newer MRI found changes consistent with resolving hemorrhage. The patient was provided immediately with recombinant human GH and aromatase inhibitor therapy to maximize GH treatment response. During follow-up, the rGH dose was adjusted based on IGF1 values, and after 3 years and 10 months, rGH treatment was stopped, reaching a height of 172.3 cm (−0.51 SD) and surpassing the initial prediction of 164.5 cm. Conclusions: Pituitary apoplexy, an even rarer complication in the pediatric population, may be associated with SARS-CoV-2 infection. Further studies are necessary to better understand the intertwining of those conditions. Full article

We present a mechanistic mathematical model of the basal state for type 2 diabetes mellitus (T2DM) in an analytical form and illustrate its use for in silico basal-state and dynamic studies. At the core of the basal-state model is a quartic equation that expresses the basal plasma glucose concentration solely in terms of model parameters. This analytical model avoids a computationally intensive numerical solver and is illustrated by an investigation of how glucose-utilization parameters impact basal glucose, insulin, insulin-dependent utilization, and hepatic extraction, leveraging median parameter values of early-stage T2DM. Furthermore, the presented basal-state model ensures accurate execution of the corresponding dynamic model, which contains basal quantities within its derivative functions; erroneous, unintended dynamics in plasma glucose, insulin, and C-peptide are illustrated using an incorrect basal glucose value. The presented basal model enables efficient and accurate basal-state and dynamic studies, facilitating the understanding of T2DM pathophysiology and the development of T2DM diagnosis, treatment, and management strategies. Full article

This study investigated the prevalence of cystic fibrosis-related diabetes (CFRD) in the Croatian cystic fibrosis (CF) population, the age at diagnosis, insulin requirements, and the relationship between age at diagnosis and other clinical parameters. Medical records from 152 patients with genetically and laboratory-confirmed CF were reviewed through to 2025. The American Diabetes Association criteria were used to diagnose CFRD. Anthropometric and clinical data were collected from the latest medical records. A total of 17 out of 152 patients had CFRD, with a prevalence of 4.8% in the paediatric population (4/84) and 19.1% in adults (13/68). The median age of CFRD diagnosis was 14 years (range 9–22 years, SD = 3.95). Thirteen patients used insulin: one used bolus only, seven used basal-bolus multiple daily injections, and five used insulin pumps. The average total daily insulin (TDI) per kilogram (kg) body weight was 0.447 U/kg (SD = 0.429). The age at CFRD diagnosis was positively correlated with the body mass index (BMI) (p = 0.029). Patients requiring insulin by age 15 had higher TDI and were more likely to have CF liver disease (p = 0.027, p = 0.037, respectively). The prevalence of CFRD and age at diagnosis aligned with previous studies. Patients diagnosed at a younger age and requiring insulin earlier had lower BMIs, likely due to a faster decline in beta cell function and earlier onset of insulinopenia. Full article

Background: Dietary consumption of insulinogenic amino acids (IAA) is known to contribute to the development of insulin resistance. It remains to be studied whether dietary IAA restriction improves glucose metabolism and insulin sensitivity and whether this improvement is related to alterations in glucose metabolism in peripheral tissues. The objective of this study was to examine the effect of IAA restriction on glucose metabolism in a piglet model. Methods: Following the acclimation period, thirty-two seven-day-old male piglets were randomly assigned into one of three groups for three weeks as follows (n = 10–11/group): (1) NR (control): basal diet without IAA restriction; (2) R50: basal diet with IAA restricted by 50%; (3) R75: basal diet with IAA restricted by 75%. IAA were alanine (Ala), arginine (Arg), isoleucine (Ile), leucine (Leu), lysine (Lys), threonine (Thr), phenylalanine (Phe), and valine (Val) as suggested by previous studies. Thermal images, body weight, and growth parameters were recorded weekly, oral glucose tolerance tests were performed on week 2 of the study, and blood and tissue samples were collected on week 3 after a meal test. Results: R75 improved glucose tolerance and, together with R50, reduced blood insulin concentration and homeostatic model assessment for insulin resistance (HOMA-IR) value, which is suggestive of improved insulin sensitivity following IAA restriction. R75 increased thermal radiation and decreased adipocyte number in white adipose tissue (WAT). R75 had a greater transcript of glucose transporter 1 (GLUT1), phosphofructokinase, liver type (PFKL), and pyruvate kinase, liver, and RBC (PKLR) in the liver and glucokinase (GCK) in WAT indicating a higher uptake of glucose in the liver and greater glycolysis in both liver and WAT. R75 increased the mRNA abundance of insulin receptor substrate 1 (IRS1) and protein kinase B (AKT1) in skeletal muscle suggestive of enhanced insulin signaling. Further, R75 had a higher mRNA of fibroblast growth factor 21 (FGF-21) in both the liver and hypothalamus and its upstream molecules such as activating transcription factor 4 (ATF4) and inhibin subunit beta E (INHBE) which may contribute to increased energy expenditure and improved glucose tolerance during IAA restriction. Conclusions: IAA restriction improves glucose tolerance and insulin sensitivity in piglets while not reducing body weight, likely through improved hepatic glycolysis and insulin signaling in skeletal muscle, and induced FGF-21 signaling in both the liver and hypothalamus. Full article

Objectives: Type 1 diabetes is characterized by hyperglycemic episodes influenced by diet, sleep quality, chronotype, and physical activity, among others. While aerobic exercise is known to improve glycemic control, its effect on blood glucose regulation remains underexplored. Thus, this case study aimed to evaluate the effects of a prolonged and differentiated indoor and outdoor exercise intervention on glycemic control in an individual with type 1 diabetes. Methods: The participant (age: 23 years; weight: 95 kg; height: 1.90 m; Body Mass Index: 26.3 kg/m²; waist to hip ratio: 0.98; basal metabolic rate: 2015 kcal; Heart Rate Maximum (HRmax): 197 beats·min⁻¹) completed two outdoor (~3800 m) and two indoor sessions with self-selected speed, in the initial 2 min stage, at a 0% grade slope. The grade increased by 2% at each stage during the uphill phase until reaching volitional fatigue, followed by a 2% decrease at each stage during the downhill phase until returning to a 0% grade. Blood pressure was assessed before and after each session. Daily nutrition intake, insulin intake, and blood glucose were continuously monitored. Dietary adherence (PREvención con DIeta MEDiterránea), sleep quality (Pittsburgh Sleep Quality Index), chronotype (Morningness–Eveningness Questionnaire), and physical activity levels (International Physical Activity Questionnaire) were assessed before each session. The Physical Activity Enjoyment Scale was used to measure enjoyment after each session. Results: The sessions were completed in ~44 and ~39 min with the participant achieving 84% (outdoor) and 96% (indoor) of their theoretical HRmax. The intervention resulted in glycemic improvements, with time spent in hyperglycemia (>250 mg/dL) decreasing from 56.46% to 0%, while time in the normal range (70–180 mg/dL) increased to 63.96%. A 47% reduction in insulin units showed that insulin sensitivity also improved. Conclusions: Despite differences in intensity, indoor and outdoor activities yielded comparable benefits, with outdoor activities being perceived as more enjoyable (outdoor: 28.5 ± 0.7; indoor: 24.0 ± 5.6) and positively impacting glycemic control, thus supporting the need for tailored strategies in diabetes management. Full article

Background/Objectives: This study compared metabolic syndrome (MetS) features in patients with Prader-Willi syndrome (PWS) to those in age-, BMI-, and gender-matched subjects with essential obesity (EOB). Methods: Thirty-two PWS patients (23 females, 9 males; median age 31.6 years; BMI 42.0 kg/m²) underwent several assessments, including anthropometric measurements, body composition via bio-impedance analysis, basal metabolic rate (BMR) using indirect calorimetry, and blood sampling. Results: Their data were compared to a matched EOB group (23 females, 9 males; median age 31.4 years; BMI 43.5 kg/m²). The study groups (PWS and EOB) were subsequently divided into two subgroups based on the International Diabetes Federation criteria for the definition of MetS. Results showed that individuals with PWS had significantly lower (p < 0.001) body weight (BW, −20.9%), height (−8.9%), fat-free mass (FFM, −23.5%), and fat mass (FM, −19.2%) in absolute terms compared to EOB subjects. However, the relative percentages of FFM and FM were similar. Absolute BMR was 25.5% (p < 0.001) lower in the PWS group; however, this difference disappeared when adjusted for FFM or body weight (BW). Metabolic outcomes were broadly similar between the groups, except for higher fasting glucose (+7.3%) and HbA1c levels (+7.9%), and lower fasting insulin (−29.0%) in PWS patients. Conclusions: Moreover, PWS subjects exhibited higher total cholesterol (+9.6%) and HDL-cholesterol (+19.8%), suggesting a more favourable lipid profile and no extra risk beyond severe obesity. Full article

This study aimed to evaluate the effects of encapsulated postbiotics derived from various probiotic microorganisms, alone or in combination with inulin, on the growth performance, carcass traits, organ weights, blood parameters, and mRNA expression of selected hormones in broilers. A total of 588 one-day-old male Ross-308 chicks were randomly designated to six replicates of seven dietary treatments (initial body weight: 40.85 ± 0.56 g, per replicate, n = 14 chicks). The treatments consisted of a basal diet (C), supplemented with encapsulated postbiotics (0.30%) derived from Lactobacillus plantarum (ELP), Bacillus subtilis (EBS), or Enterococcus faecium (EEF), as well as combinations of these encapsulated postbiotics with 1.0% inulin (ELPI, EBSI, and EEFI) for six weeks. The results demonstrated that the body weight and body weight gain of birds that were fed diets supplemented with encapsulated postbiotics or their combinations with inulin significantly increased in comparison to the C group (p < 0.001). Feed intake (FI) remained unaffected during days 1–21, as did feed conversion ratios (FCR) during days 22–42, and days 1–42 demonstrated no significant differences (p > 0.05). However, FCR improved during days 1–21, and FI increased during days 22–42 and 1–42 (p < 0.05). Carcass yield, including breast, thigh, and abdominal fat yields, was enhanced (p < 0.001). Although the relative weights of the heart, spleen, pancreas, and liver were unaffected (p > 0.05), the relative weight of the bursa of Fabricius increased (p < 0.001). Serum antioxidant status and immunoglobulin A and M levels were higher, while liver enzymes, cholesterol, triglycerides, and total oxidant status were lower in the supplemented groups compared to the control group (p < 0.001). Serum glucose and protein levels remained unchanged (p > 0.05). The mRNA expression of growth hormone and insulin-like growth factor was upregulated in the supplemented groups (p < 0.001). In conclusion, encapsulated postbiotics (0.30%) derived from different probiotics, alone or combined with inulin (1.0%), positively influenced growth performance, carcass traits, and immunity in male broilers. Full article

Integration of old and recent experimental data consequences is needed to correct and help improve the hypothetical mechanism responsible for the stimulus–secretion coupling mechanism of glucose-induced insulin secretion. The main purpose of this review is to supply biochemical considerations about some of the metabolic pathways implicated in the process of insulin secretion. It is emphasized that glucose β-cells’ threshold to activate secretion (5 mM) might depend on the predominance of anaerobic glycolysis at this basal glucose concentration. This argues against the predominance of phosphoenolpyruvate (PEP) over mitochondrial pyruvate oxidation for the initiation of insulin secretion. Full quantitative and qualitative reproduction, except the threshold effect, of glucose-induced insulin release by a permeable methylated analog of succinic acid indicates that mitochondrial metabolism is enough for sustained insulin secretion. Mitochondrial PEP generation is skipped if the GABA-shunt pathway is exclusively coupled to the citric acid cycle, as proposed in the “GABA-shunt” model of stimulus–secretion coupling. Strong or maintained depolarization by KCl or sulfonylureas might induce the opening of β-cells Cx36 hemichannels, allowing the loss of adenine nucleotides and other metabolites, mimicking the effect of an excessive mitochondrial ATP demand. A few alterations of OxPhos (Oxidative Phosphorylation) regulation in human T2D islets have been described, but the responsible mechanism(s) is (are) not yet known. Finally, some experimental data arguing as proof of the relative irrelevance of the mitochondrial function in the insulin secretion coupling mechanism for the initiation and/or sustained stimulation of hormone release are discussed. Full article

Background: Phytochemicals possess diverse therapeutic potential; however, the impact of arene substitutions on the pharmacological properties of the bibenzyl compounds batatasin III and gigantol, derived from Dendrobium venustum, remains unexplored. Objectives: This study examines how structural differences between these compounds affect cellular glucose uptake and lipid metabolism during adipocyte differentiation. Methods: The effects of both bibenzyl compounds on cytotoxicity and glucose uptake were assessed in mouse and human pre-adipocytes and rat skeletal muscle myoblasts using colorimetric assays. Lipid metabolism was evaluated through Oil Red O staining and quantification of triglyceride and glycerol levels, while protein and gene expression during adipocyte differentiation were analyzed via western blotting and RT-qPCR. Results: At the highest non-cytotoxic concentration (25 µM), gigantol significantly enhanced glucose uptake (up to 2-fold) under both basal and insulin-stimulated conditions, whereas batatasin III showed a similar effect only under basal conditions. Gigantol upregulated GLUT1 and GLUT4 in myotubes but downregulated them in adipocytes, whereas batatasin III had minimal impact on these transporters. Both compounds suppressed lipid accumulation in mouse and human adipocytes by decreasing intracellular triglyceride content and promoting extracellular glycerol release. However, batatasin III did not affect extracellular glycerol release during early adipocyte differentiation, as evidenced by the marked downregulation of key lipogenic proteins (PLIN1, LPL, FABP4) observed only with gigantol. Molecular docking analyses suggest that gigantol’s greater bioactivity may result from its higher number of arene substitutions. Conclusions: This study provides the first evidence that differences in arene substitutions among orchid-derived bibenzyls influence their pharmacological properties. Our findings support the strategic modification of natural products as a potential approach for managing metabolic disorders. Full article

The last two decades have proffered many remarkable choices in managing type 1 and type 2 diabetes mellitus. Leading the list are glucagon-like peptide-1 receptor agonists (GLP1RAs), the first of which, exenatide, was approved by the FDA in 2005. Two other major classes of drugs have also entered the market: dipeptidyl peptidase-4 (DPP-4) inhibitors, commonly known as gliptins and approved in 2006, and sodium–glucose cotransporter-2 (SGLT-2) inhibitors, with the first approval occurring in 2013. These drugs have revolutionized the treatment of diabetes. Additionally, on the horizon, the once-weekly basal insulin analog insulin icodec and the once-weekly combination of insulin icodec and semaglutide are expected to be available in the future. Beyond glycemic control, GLP1RAs have exhibited benefits in conditions associated with diabetes, including hypertension, dyslipidemia, non-alcoholic steatohepatitis, as well as in neurodegenerative diseases such as Alzheimer’s disease. Additionally, emerging research suggests potential roles in certain types of cancer, infertility, and associative learning. Major cardiovascular events seem to be lower in patients on GLP1RAs. While some evidence is robust, other findings remain tenuous. It is important that clinicians are familiar with current research in order to provide optimal evidence-based care to patients. In the not-too-distant future, there may be a case to prescribe these drugs for benefits outside diabetes. Full article

Background and Clinical Significance: Lung cancer, a leading cause of global cancer diagnoses, maintains the highest mortality risk despite advances in treatment. Immunotherapy agents, such as anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1), have revolutionized care for non-small cell lung cancer (NSCLC). However, the success is tempered by the emergence of immune-mediated adverse reactions, including the rare onset of type I diabetes. The incidence of diabetes mellitus increased during the SARS-CoV-2 pandemic. While there are several cases of new-onset diabetes after COVID-19 and COVID-19 vaccination, no case of new-onset type 1 diabetes after COVID-19 was described in an immune checkpoint inhibitor (ICI)-treated patient. Case Presentation: A 57-year-old male with stage IV NSCLC (brain and liver metastases) who had been treated with nivolumab for 4 years appeared positive for SARS-CoV-2 infection at a routine check. After two weeks, he was admitted to our clinic with severe fatigue, hyperglycemia, hyponatremia, and hyperkalemia. HbA1c level was normal and serum peptide C was undetectable. Nivolumab treatment was ceased, and the patient became fully dependent on basal–bolus insulin. After 3 months, the patient showed a complete imagistic remission. Conclusions: The case presented significant challenges due to the unclear etiology of newly onset diabetes and the uncommon age at which type 1 diabetes is developed. The outcome suggests that anti-PD-1 and SARS-CoV-2 infection can act synergistically. Full article