Decrease In Glucose Concentration Research Articles

Aquaporin-1 Facilitates Macrophage M1 Polarization by Enhancing Glycolysis Through the Activation of HIF1α in Lipopolysaccharide-Induced Acute Kidney Injury.

This study aimed to investigate how aquaporin 1 (AQP1) modulates hypoxia-inducible factor-1α (HIF1α) to promote glycolysis and drive the M1 polarization of macrophages. Within 12 h post-treatment with LPS to induce acute kidney injury in rats, a significant upregulation of AQP1 and HIF1α protein levels was noted in serum and kidney tissues. This elevation corresponded with a decrease in blood glucose concentrations and an enhancement of glycolytic activity relative to the control group. Furthermore, there was a pronounced reduction in the circulating levels of the anti-inflammatory cytokine IL-10, accompanied by an upregulation in the levels of the pro-inflammatory cytokines IL-6 and TNF-α. The administration of an HIF1α inhibitor reversed these effects, which did not affect the production of AQP1 protein. In cellular assays, AQP1 knockdown mitigated the increase in HIF1α expression induced by LPS. Furthermore, the suppression of HIF1α with PX-478 led to decreased expression levels of Hexokinase 2 (HK2) and Lactate Dehydrogenase A (LDHA), indicating that AQP1 regulates glycolysis through HIF1α. M1 polarization of macrophages was reduced by AQP1 knockdown and was further diminished by the addition of an HIF1α inhibitor. Inhibition of the glycolytic process not only weakened M1 polarization but also promoted M2 polarization, thereby reducing the release of inflammatory cytokines. These findings provide a novel perspective for developing therapeutic strategies that target AQP1 and HIF1α, potentially improving the treatment of sepsis-associated AKI.

Prenatal stress induces sex- and tissue-specific alterations in insulin pathway of Wistar rats offspring.

Prenatal stress may lead to tissue and sex-specific cardiometabolic disorders in the offspring through imbalances in the insulin signaling pathway. Therefore, we aimed to determine the sex-specific adaptations of prenatal stress on the insulin signaling pathway of cardiac and hepatic tissue of adult offspring Wistar rats. Wistar pregnant rats were divided into control and stress groups. Unpredictable stress protocol was performed from the 14th to the 21st day of pregnancy. After lactation, the dams were euthanized and blood was collected for corticosterone measurement and the offspring were separated into four groups according to sex and intervention (n=8/group). At 90 days old, the offspring were submitted to an oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT). After euthanasia blood collection was used for biochemical analysis and the left ventricle and liver were used for protein expression and histological analysis. Stress increased maternal corticosterone levels, and in the offspring, decreased glucose concentration in both OGTT and ITT, reduced insulin receptor (Irβ) and insulin receptor substrate-1 (IRS1) activation and reduced insulin receptor inhibition (PTP1B) in the liver of male offspring at 90 days old, without repercussions in cardiac tissue. Moreover, female offspring submitted to prenatal stress exhibited reduced fatty acid uptake, with lower hepatic CD36 expression, reduced high density lipoprotein (cHDL) and increased Castelli risk indexes I and II. Unpredictable prenatal stress evoked reduced insulin sensitivity and liver-specific impairment in insulin signaling activation in male while increasing markers of cardiovascular risk in females.

Enhancement of β-galactosidase catalytic activity and stability through covalent immobilization onto alginate/tea waste beads and evaluating its impact on the quality of some dairy products

The current study aimed to evaluate the hydrolysis of whole fat milk (WFM) and sweet whey (SW) using β-galactosidase (β-gal) after covalent immobilization onto activated alginate/tea waste (Alg/TW) beads as a novel carrier. The optimum temperature for free and Alg/TW/β-gal was 40 °C and the ideal pH was 7.0. However, Alg/TW/β-gal displayed better stabilities at high temperatures and a wide pH range. Additionally, the value of Km and Vmax for Alg/TW/β-gal was higher than the free enzyme. The Alg/TW/β-gal showed better residual activity (78.6 %) after 90 storage days at 4 °C. The reusability of Alg/TW/β-gal was very good as it conserved its full activity after 15 consecutive cycles and conserved 93 % of its initial activity after 10 cycles with ONPG (O-nitrophenyl-β-D-galactopyranoside) and lactose as a substrate, respectively. The impact of Alg/TW/β-gal on WFM and SW using HPLC analysis revealed a remarkable decrease in lactose concentration and increase of glucose and galactose concentrations. The SW exhibited higher degree of lactose hydrolysis (97.3 %) compared to WFM (62.4 %). Besides, SW had a prominent increase in total phenolic content (96.8 mg/L) compared to WFM (54.3 mg/L). The antioxidant activity had increased after enzyme treatment in both WFM and SW. The GC–MS analysis for volatile compounds identified twenty-five flavour constituents. Finally, Alg/TW/β-gal has a potential application for obtaining healthy, acceptable, and commercial dairy products of low lactose.

Serum metabolome analysis reveals medicinal fungi Phellinus igniarius ameliorated type 2 diabetes mellitus indications in rats via modulation of amino acid and carbohydrate metabolism.

Medicinal fungi Phellinus igniarius exhibited hypoglycemic effects; however, the protective mechanisms of P.igniarius on type 2 diabetes are not yet fully understood. Herein, the anti-diabetic effect of P.igniarius was investigated via gas chromatography-mass spectrometry (GC/MS)-based metabolome analysis. The rats were divided into normal group; model group; positive group; and groups treated with low, medium, and high dose of P.igniarius. After the treatments, a significant decrease in blood glucose concentration was observed. The levels of total cholesterol and triglyceride were dramatically decreased, whereas the level of insulin was increased. Multivariate statistical analysis revealed 31 differential endogenous metabolites between model group and normal group. A total of 14, 28, and 31 biomarkers were identified for low, medium, and high dose of P.igniarius treated groups, respectively. Twenty-one of the biomarkers were validated by using standard substances. The linear correlation coefficients ranged from 0.9990 to 1.0000. The methodology exhibited good repeatability, recoveries, and stability. The major intervened metabolic pathways covered glyoxylate and dicarboxylic acid metabolism; alanine, aspartate, and glutamate metabolism; and glycine, serine, and threonine metabolism. Our metabolome analysis has provided insights into the underlying mechanism of P.igniarius on type 2 diabetes.

Simulating the impact of greenspace exposure on metabolic biomarkers in a diverse population living in San Diego, California: A g-computation application.

Growing evidence exists that greenspace exposure can reduce metabolic syndrome risk, a growing public health concern with well-documented inequities across population subgroups. We capitalize on the use of g-computation to simulate the influence of multiple possible interventions on residential greenspace on nine metabolic biomarkers and metabolic syndrome in adults (N = 555) from the 2014-2017 Community of Mine Study living in San Diego County, California. Normalized difference vegetation index (NDVI) exposure from 2017 was averaged across a 400-m buffer around the participants' residential addresses. Participants' fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations, systolic and diastolic blood pressure, hemoglobin A1c (%), waist circumference, and metabolic syndrome were assessed as outcomes of interest. Using parametric g-computation, we calculated risk differences for participants being exposed to each decile of the participant NDVI distribution compared to minimum NDVI. Differential health impacts from NDVI exposure by sex, ethnicity, income, and age were examined. We found that a hypothetical increase in NDVI exposure led to a decrease in hemoglobin A1c (%), glucose, and high-density lipoprotein cholesterol concentrations, an increase in fasting total cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations, and minimal changes to systolic and diastolic blood pressure, waist circumference, and metabolic syndrome. The impact of NDVI changes was greater in women, Hispanic individuals, and those under 65 years old. G-computation helps to simulate the potential health benefits of differential NDVI exposure and identifies which subpopulations can benefit most from targeted interventions aimed at minimizing health disparities.

A Review of Sotagliflozin: The First Dual SGLT-1/2 Inhibitor.

Sotagliflozin (trade name INFEPA) is a novel dual sodium-glucose cotransporter-1 and -2 (SGLT-1/2) inhibitor that was developed by Lexicon Pharmaceuticals. It has emerged as a promising therapy for managing heart failure and other cardiovascular complications associated with type 2 diabetes mellitus (T2DM). Its dual inhibition of SGLT-1 and SGLT-2 receptors uniquely decreases glucose absorption in the intestine in addition to decreasing renal glucose reabsorption, leading to improved glycemic control and cardio-reno protection. Clinical trials have demonstrated its efficacy in reducing cardiovascular death, heart failure hospitalizations, and urgent visits, particularly in T2DM patients with chronic kidney disease (CKD). The drug was approved in 2023 by the Food and Drug Administration for reducing cardiovascular death and heart failure in T2DM patients with CKD and those with heart failure, irrespective of diabetic status or ejection fraction. However, despite its considerable therapeutic potential, sotagliflozin does pose notable adverse effects, including diabetic ketoacidosis, genital infections, and diarrhea. As a result, it has faced regulatory challenges in certain regions, notably the United States. The Food and Drug Administration has so far withheld approval for sotagliflozin in the treatment of type 1 diabetes due to concerns about its safety profile, specifically the risk of diabetic ketoacidosis, although Lexicon Pharmaceuticals plans to submit another new drug application for this use in 2024. Further investigation and clinical trials are warranted to fully elucidate sotagliflozin's impact on diabetes and CKD.

How pre-analytical conditions impact glucose measurement and (gestational) diabetes diagnosis: A real-world stability study and a call for harmonization

Background and aimsSince 2023, guidelines of the AACC/ADA recommend the use of citrate buffer-containing tubes as a first option for glucose measurement. This study aims to assess the pre-analytical stability of glucose under various conditions (room temperature (RT) or at 4 °C) and the potential real-world impact of introducing these tubes on (gestational) diabetes and IFG prevalence. Materials and Methods25 healthy volunteers were sampled to assess glucose stability across time, at 4 °C and at RT, before and following centrifugation. 701 patients undergoing fasting plasma glucose analysis and 109 women having OGTT were collected according to current procedures (NaFl K2C2O4 (NaFl) tubes) as well as with citrate-containing tubes (FC Mix). ResultsThe mean glucose concentration bias between FC Mix and NaFl tubes when centrifugation occurred within 5 min was 0.53 % and this difference raised slowly to reach 2.3 %, six-hours post-centrifugation. When centrifugation was delayed, a rapid decrease in glucose concentrations was observed for NaFl tubes (4.9 % at 30 min) and this trend was only partially reduced by placing samples at 4 °C (3.1 %). The decrease reached 10.8 % (RT) and 7.8 % (4 °C) at 2 h, before reaching a plateau. Samples collected on citrate remained stable during 24 h. In real-life conditions, the mean bias between FC Mix and NaFl tubes increased progressively over time and reached 8.59 % for samples centrifuged between two- and four-hours following sampling. Compared to widespread practices, the use of citrate-containing tubes increased IFG, DM and GDM prevalences by 84.0 %, 36.7 % and 150 %, respectively. ConclusionsGlucose concentrations rapidly decrease in NaFl tubes following collection and placing samples at 4 °C reduces only marginally the decay. Citrate-containing tubes offer a valuable solution for direct and long-lasting glucose stabilization but, before wider adoption, large epidemiologic studies should confirm or redefine current diabetes diagnostic thresholds.

Effect of glycerol supplementation in early lactation on metabolic health, milking activity, and production of dairy cows in automated milking system herds

The objective of this study was to quantify the effects of supplementing early-lactation cows with a dry pure glycerol product, delivered through the automated milking system (AMS) concentrate, in the first 21 d in milk (DIM) on metabolic markers, milking behavior, and milk production. In 5 commercial AMS dairy herds, 389 dairy cows were randomly assigned, controlling for parity, 21 d before expected calving to 1 of 2 treatments, within farm: (1) control group (CON) receiving the standard AMS pellet (n = 213) from 1 to 150 DIM, or (2) glycerol group (GLY) receiving the treatment AMS pellet (n = 176) formulated to deliver 250 as fed g/d of glycerol product from 1 to 21 DIM (mean actual = 249 g/d dry matter [DM]), then they received the standard AMS pellet from 22 to 150 DIM. Across all farms, cows were fed partial mixed rations (PMR) that were similar in ingredient and nutrient composition. One prepartum blood sample and 5 postpartum blood samples were collected from each cow to determine serum nonesterified fatty acids (NEFA), blood β-hydroxy butyrate (BHB), and blood glucose concentrations. Cow body condition score (BCS) was recorded every 21 d from -21 to 63 DIM. Data were collected and analyzed for the treatment period (1 to 21 DIM) and a follow-up period (22 to 150 DIM). There was no detected treatment effect on serum NEFA concentrations in the first week of lactation. There was a treatment by time interaction for blood BHB and blood glucose, where GLY cows tended to have increased BHB concentrations at 5 DIM and had decreased glucose concentrations at 9 and 12 DIM. There was an interaction of BCS with treatment on the incidence of BHB ≥1.2 mmol/L, whereby over-conditioned CON cows (BCS ≥3.5) were 3.5x more likely to have a high BHB test than CON cows with normal prepartum BCS. During the treatment period GLY cows had 0.1 ± 0.05 more successful milkings/d, were delivered 0.27 ± 0.05 DM kg/d more AMS concentrate and tended to yield 0.8 ± 0.47 kg/d more milk. During the follow-up period GLY cows had 0.1 ± 0.04 more successful milkings/d, were delivered 0.18 ± 0.06 DM kg/d more AMS concentrate, and yielded 1.5 ± 0.53 kg/d more milk than CON cows. Glycerol supplementation allowed cows to maintain better BCS, as GLY cows lost less BCS from calving to 63 DIM than CON cows. Overall, the results of this study demonstrate that supplementing pure glycerol through the AMS concentrate for the first 21 DIM can reduce BCS loss in early lactation, improve milking behavior, and increase milk yield to mid lactation.

Acute Consumption of Cooked Green Banana Pulp Beverage (Musa cavendishii) Decreases Plasma Glucose in Healthy Women: A Cross-Sectional Controlled Study.

This study aimed at comparing the carbohydrate composition of three banana varieties (cv. Nanica, Nanicão, and Prata) and investigating the effect of a single dose of cooked green banana pulp beverage (GBPd) on plasma glycemic homeostasis indexes (glucose, PYY, GIP, insulin) and hunger and satiety sensation (visual analog scale-VAS). The bananas were classified according to the color scale. The fiber, total carbohydrate, and resistant starch (RS) were determined using validated methods. Glucose homeostasis indexes and hunger/satiety sensation were determined in ten healthy women in two stages before and after intake: (1) glucose solution (250g/L); (2) one week later, consumption of the glucose solution plus 75g/L of GBPd. Blood samples were collected twice in stage-1 and every 15min for 2h in stage-2. Cv. Nanicão was selected, because it presented a higher content in RS and dietary fiber on dry base than the other cultivars. Thus, it was used to test glycemic response. After 2h of GBPd intake, no difference was observed in hunger/satiety sensation and plasma glycemic homeostasis indexes, except for a decrease in plasma glucose concentration (-15%, p = 0.0232) compared to stage-1. These results suggest that cv. Nanicão has a higher potential as a functional ingredient and can influence the reduction in the glycemic index of a meal compared to other cultivars. However, it had not a short-term effect on hormones GIP and PYY in healthy women. Further research is needed to understand the long-term effects and mechanisms of green banana on glycemic control and satiety.

Overexpression of ubiquitin-conjugating enzyme 2T induces radiotherapy resistance in hepatocellular carcinoma by enriching regulatory T cells in the tumor microenvironment

To investigate the effect of overexpression of ubiquitin-conjugating enzyme 2T (UBE2T) on radiosensitivity of hepatocellular carcinoma (HCC). Hepa1-6 cells were transfected with a UBE2T-overexpressing or a control lentiviral vector, and the changes in their radiotherapy sensitivity and concentrations of glucose and lactate in the supernatant were assessed using colony-forming assay and colorimetric assay. The transfected cells were inoculated subcutaneously in nude mice or C57BL/6 mice, and tumor growth following irradiation were recorded. The xenografts were collected for analyzing infiltration of CD4+ T cells and regulatory T cells (Tregs) using flow cytometry and detecting expressions of HK1 and LDHA using Western blotting. The correlations of UBE2T expression with immune cell infiltration, glycolysis and Tregs in HCC were analyzed using CIBERSORT algorithm and TCGA database, and the results were verified in a co-culture system of Hepa1-6 cells and Tregs. UBE2T overexpression caused radiotherapy resistance in both cultured Hepa1-6 cells and xenografts in the tumor-bearing mouse models (especially in C57BL/6 mice). CIBERSORT analysis suggested that a high expression of UBE2T was associated with increased percentages of dendritic cells, T follicular helper cells, M2 macrophages, monocytes, lymphocytes and Tregs in HCC. The UBE2T-overexpressing xenografts showed an increased percentage of Tregs and enhanced expressions of HK1 and LDHA, and irradiation increased infiltration of CD4+ T cells and Tregs in the tumor microenvironment. Hepa1-6 cells overexpressing UBE2T showed a decreased glucose concentration and an increased lactate concentration. GSEA analysis suggested that a high UBE2T expression was positively correlated with increased glycolysis and Tregs infiltration in HCC. In the cell co-culture system, UBE2T overexpression significantly enhanced lactate production, proliferation and immunosuppressive functions of Tregs. A high UBE2T expression results in radiotherapy resistance of HCC possibly by enhancing glycolysis and cause enrichment of Tregs in the tumor microenvironment.

327-OR: Does Exercise in Cool Water Result in a Greater Decrease in Blood Glucose Concentration than Exercise in Thermoneutral Water or on Land in People with Type 1 Diabetes?

327-OR: Does Exercise in Cool Water Result in a Greater Decrease in Blood Glucose Concentration than Exercise in Thermoneutral Water or on Land in People with Type 1 Diabetes?

#1316 Sirtuin 3 promotes renal gluconeogenesis in fibrotic kidneys

Abstract Background and Aims Decreased renal gluconeogenesis is currently identified as a hallmark of chronic kidney disease (CKD), which may contribute to renal fibrosis. Sirt3 is a crucial metabolic sensor that regulates ATP generation, mitochondrial adaptive response to stress, and glucose metabolism. It has been shown that Sirt3 is renal protective in fibrotic kidneys, however its underlying mechanisms is not completely known. In this study, we aimed to investigated whether Sirt3 inhibits CKD associated renal fibrosis through restoring renal gluconeogenesis. Method 1. Animal model of renal fibrosis (in vivo) For unilateral ureter obstructed (UUO) mouse model, a. Twenty-eight C57 mice were divided into four groups: sham + Vehicle, UUO + Vehicle, UUO + 3-TYP and UUO + HKL group. Mice were treated with saline or 20 mg/kg 3-TYP, an inhibitor of SIRT3 or 1 mg/kg HKL, an activator of SIRT3 daily (i.p.). b. Fourteen C57 mice were divided into two groups: Ad-Sirt 3 or Ad-LacZ (0.5 × 109 pfu/100 μL) was injected into the left renal artery before the UUO operation. Systemic glucose metabolism was evaluated by insulin and glucose tolerance tests. 7 or 14 days after operation, kidney tissues were collected and performed histopathological and molecular examination. 2. Primary murine renal tubules fibrosis (ex vivo) Primary renal tubules were isolated from C57 mouse of 4 weeks of age. 5 ng/mL TGF-β was added to culture medium for inducing fibrosis. After this Sirt3 was inhibited by 3-TYP (25 μm) or activated by HKL (2 μm) or overexpressed by adenovirus for different time periods (1, 3, 24, 48 hours). Protein or RNA samples were taken to evaluate renal fibrosis and gluconeogenesis. 3. Human renal epithelial (HK2) cells culture and treatment (in vitro) TGF-β stimulated HK2 cells were used as an in vitro model. Sirt3 was inhibited by 3-TYP or activated by HKL or overexpressed by adenovirus. Protein and RNA samples were taken to evaluate renal fibrosis and gluconeogenesis. Glucose and lactate were measured in supernatant of culture medium. Results In vivo, Masson staining showed that 3-TYP treatment increased the tubulointerstitial collagen deposition of UUO kidneys (Fig. 1A). WB results indicated that 3-TYP enhanced the increased expression of fibrotic marks (Fibronectin, Collagen-I, Vimentin) (Fig. 1B), and further reduced the expression of gluconeogenesis limitation enzyme (PCK1, FBP1) and transcription factors (PGC-1α and FOXO1) 14 days after UUO operation (Fig. 1C). Conversely, HKL treatment or overexpression of Sirt3 in UUO kidney reduced expression of fibrotic marks, increased the expression of gluconeogenesis markers (Fig. 1D-E). 3-TYP increased the lactate concentration in UUO kidneys (Fig. 1F). Insulin sensitivity and glucose clearance tests showed that treatment with 3-TYP further damaged the glucose homeostasis in UUO mice (Fig. 1G-J). Ex vivo, q-PCR results showed that the mRNA of Sirt3 was significantly decreased by time after TGF-β stimulation while the mRNA of FN, Snail was up-regulated and PCK1 and FBP1 were down-regulated (Fig. 2A-D). WB showed that 3-TYP treatment inhibited the expression of PCK1, FBP1 and PGC-1α, FOXO1 (Fig. 2E), however, HKL treatment or overexpressed of Sirt3 by adenovirus increased the expression of gluconeogenesis markers respectively in primary renal tubules (Fig. 2F). In vitro, WB showed that transfection of Sirt3 increased the expression of gluconeogenesis markers and decreased the expression of fibrotic marks of HK2 cells in a fibrotic condition (Fig. 3A-B). Moreover, 3-TYP treatment further decreased the mRNA expression of PCK1 and FBP1 in TGF-β stimulated HK2 cells (Fig. 3C-D). The increased lactate concentration and decreased glucose concentration in the culture medium of TGF-β stimulated HK2 cells were further escalated after 3-TYP treatment (Fig. 3E-F) while reversed after overexpression of Sirt3 (Fig. 3G-H). Conclusion Sirt 3 promotes renal gluconeogenesis in fibrotic kidneys through up-regulation of renal gluconeogenic enzyme PCK1 and FBP1 expression, which is associated with activation of renal metabolic transcription factors PGC-1α and FOXO1.

#2495 Renal and peritoneal protective effects of SGLT2 Inhibitors in incident peritoneal dialysis (PD) patients

Abstract Background and Aims The renoprotective effect of SGLT2 inhibitors has been evaluated in several large studies, but renal function of the subject is defined as eGFR≥20-30 mL/min/1.73 m2 or higher in most studies. On the other hand, SGLT2 is expressed in the peritoneum, and there have been reports of decreased glucose absorption and improvement of ultrafiltration injury with SGLT2 inhibitors in animal studies. However, there are very few reports on the protective effects of SGLT2 inhibitors on renal and peritoneal function in PD patients. In the present study, we retrospectively evaluated the renal and peritoneal protective effects of SGLT2 inhibitors in patients undergoing PD. Method Among the patients who received PD at our hospital, 8 patients who continued SGLT2 inhibitors and underwent peritoneal equilibrium testing (PET) at the time of induction and 1 year after induction were assigned to the SG group, and 32 patients who received PD without SGLT2 inhibitors were assigned to the control group. PET data, PD drainage volume, urine output, renal • peritoneal • total Kt/V, and renal • peritoneal • total weekly CCr at the time of PD induction and 1 year after PD induction were compared retrospectively. Results Among the 40 patients, the median age was 64 years (interquartile range 52-71), with 33% males, and the median eGFR at PD induction was 5.25 ml/min/1.73 m2. The most common cause of end-stage renal failure was diabetic nephropathy (37.5%), followed by chronic glomerulonephritis (15.0%) and nephrosclerosis (12.5%). At the time of induction of peritoneal dialysis, there were no significant differences between the SG group and the control group in PET data, PD drainage volume, urine output, renal • peritoneal • total Kt/V and weekly CCr. However, at one year after PD induction, urine volume, renal • total Kt/V, and renal weekly CCr were higher in the SG group. Total weekly CCr at 1 year of PD induction was significantly higher in the SG group (p = 0.03). Multivariate linear regression analysis showed that SGLT2 inhibitors were independently associated with total weekly CCr at 1 year after PD induction (p = 0.04). Conclusion Our results suggest that SGLT2 inhibitors may have renal and peritoneal protective effects in patients undergoing PD induction. For CKD stage G4 and 5 patients scheduled for PD induction in the future, proactive continuation of SGLT2 inhibitors may be effective in preserving renal and peritoneal function.

A Biochemical and Histological Assessment of Postmortem Changes to the Eyes of Domestic Pigs: A Preliminary Study.

The Postmortem Interval (PMI) is the time from the death of an animal to its discovery. From a veterinary forensic standpoint, an accurate estimation of the PMI is of particular importance, especially with the observed increase in deaths of domestic and wild animals. A preliminary study was conducted using the eyes of domestic pigs. A biochemical analysis was conducted on the vitreous humor of the eye, whilst a histological analysis was conducted on the retina. The eyes were stored at +4 °C and changes were assessed at time intervals of 0, 12, 24, 48, and 120 h. The biochemical analysis during the PMI established a decrease in sodium, chlorine, and glucose concentrations, and a rise in potassium concentration. Accordingly, a simple linear regression showed a significant correlation between changes in concentrations of sodium (Na+), potassium (K+), chloride (Cl-), and glucose, in relation to the PMI. The histological analysis showed evident morphological changes in the retina, which included homogenization of the rod and cone cells, pyknosis of the outer nuclear layer, homogenization of the outer plexiform layer, pyknosis of the inner nuclear layer, homogenization of the inner plexiform layer, and pyknosis of the nuclei of the ganglion layer of the retina.

Anti-diabetic effect of <i>Eucalyptus camaldulensis</i> (Red gum) leaf-supplemented diet in streptozotocin-induced diabetic rats

Purpose: To investigate the potential anti-diabetic effect of supplementing a diet with Eucalyptus camaldulensis leaves in streptozotocin (STZ) induced Wistar rats. 
 Methods: Methanolic extract of E. camaldulensis was screened using gas chromatography-mass spectrometric analysis. After that, eighteen animals were separated into three groups: Group A served as control group. Group B, the diabetic control group, was induced with STZ, and Group C was induced with STZ and fed a 10 % E. camaldulensis leaf-supplemented diet for 14 days. Thereafter, rats were sacrificed, and fasting blood was collected for serum glucose, enzyme and protein activity tests. Organs were excised for biochemical and histological analysis. 
 Results: The GC-MS fingerprint identified 17 constituents, with 2-hydroxy carbazole being the most abundant. Rats on the E. camaldulensis leaf-based diet for 14 days exhibited a significant decrease (p < 0.05) in serum glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, albumin, total bilirubin, urea, and creatinine concentrations compared to diabetic controls. Insulin levels significantly increased (p < 0.05). Additionally, the E. camaldulensis diet led to a significant decrease in serum lipid profile levels but increased high-density lipoprotein cholesterol (HDL-C). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities increased significantly, while malondialdehyde levels decreased significantly (p < 0.05). Histopathology revealed positive effects on hepatocytes, acini, pancreatic duodenal lymphoid activation, islets of Langerhans resurgence, and normal kidneys. 
 Conclusion: Eucalyptus camaldulensis leaf-supplemented diet demonstrates anti-diabetic, hypolipidemic and antioxidant enzyme activities. Carbazole identified by GC-MS may be the potential anti-diabetic and hypolipidemic agent in E. camaldulensis leaf-based diet.

Effect of phenylbutazone on insulin secretion in horses with insulin dysregulation.

Phenylbutazone is often prescribed to manage pain caused by hyperinsulinemia-associated laminitis, but in diabetic people nonsteroidal anti-inflammatory drugs increase insulin secretion and pancreatic activity. Investigate the effect of phenylbutazone administration on insulin secretion in horses. It was hypothesized that phenylbutazone will increase insulin secretion in horses with insulin dysregulation (ID). Sixteen light breed horses, including 7 with ID. Randomized cross-over study design. Horses underwent an oral glucose test (OGT) after 9 days of treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). After a 10-day washout period, horses received the alternative treatment, and a second OGT was performed. Insulin and glucose responses were compared between groups (ID or controls) and treatments using paired t test and analyses of variance with P < .05 considered significant. In horses with ID, phenylbutazone treatment significantly decreased glucose concentration (P = .02), glucose area under the curve (2429 ± 501.5 vs 2847 ± 486.1 mmol/L × min, P = .02), insulin concentration (P = .03) and insulin area under the curve (17 710 ± 6676 vs 22 930 ± 8788 μIU/mL × min, P = .03) in response to an OGT. No significant effect was detected in control horses. Phenylbutazone administration in horses with ID decreases glucose and insulin concentrations in response to an OGT warranting further investigation of a therapeutic potential of phenylbutazone in the management of hyperinsulinemia-associated laminitis beyond analgesia.

Effect of Arterialization on Venous Blood Glucose Concentrations and Implications for Observed Continuous Glucose Monitoring Accuracy.

Background: Heating of the arm and/or hand ("arterialization") is sometimes used in continuous glucose monitoring (CGM) performance studies with the reported aim of reducing differences between venous and capillary glucose concentrations. In this study, the effect of heating on venous glucose concentrations and CGM accuracy was investigated. Methods: A heating pad set to 50°C (122°F) was used with 20 participants to heat either the dominant or nondominant arm and hand. Venous and capillary samples were obtained every 15 min on both arms throughout each of three 6-h glucose challenges. CGM sensors were worn on each upper arm for each of the three visits. Results: Heating of the arm led to a median increase in venous glucose concentrations of +1.4%. No similar effect on capillary concentrations was observed. As a result, the median capillary to venous difference decreased from +5.9% in the nonheated arm to +4.2% in the heated arm. CGM accuracy observed in this study was affected by the selection of heated venous, nonheated venous, or capillary glucose concentrations as comparator data. The heating effect was more pronounced with rapidly decreasing glucose concentrations. Temperatures on the skin did not exceed 40°C (104°F). No adverse events or protocol deviations were associated with the use of the heating pad. Conclusions: Heating of the arm led to a small increase in venous glucose concentrations, but venous concentrations did not reach the level of capillary glucose concentrations. CGM accuracy observed in this study varied depending on the selected comparator data. This study was registered at the German Clinical Trials Register (DRKS00031197).

Effect of paprika extracts on growth performance, haemolymph chemistry, intestinal microbiota and antioxidant enzyme activities of white-leg shrimp (Litopenaeus vannamei).

This study aims to evaluate the effects of paprika extract on the survival rate, growth performance and stimulation of the innate immune system of Litopenaeus vannamei. In this experiment, 240 healthy shrimp (3.22 ± 0.12 g) were randomly divided into four groups. The shrimp were fed diets with different concentrations of paprika oil extracts (0%, 0.5%, 1% and 2%) for 8 weeks. The results showed that growth performance, urea, uric acid, creatinine, cholesterol levels, aspartate aminotransferase and alkaline phosphatase activities were not significantly affected by adding paprika extract to the shrimp diet (p > 0.05). Diets containing 1% and 0.5% paprika extract showed the highest levels of total protein and triglyceride, respectively (p < 0.05). There was a significant decrease in haemolymph glucose concentration in shrimp-fed diets containing 1% and 2% paprika extract (p < 0.05). Moreover, a diet containing 0.5% paprika extract resulted in the highest levels of total heamocyte count, hyaline cells and large-granular cells in shrimp (p < 0.05). Higher catalase and superoxide dismutase activities were also exhibited in the paprika groups (p < 0.05). Vibrio sp. bacteria were not significantly reduced by paprika extract in the intestines of L. vannamei (p > 0.05). A significant decrease in heterotrophic bacteria was observed with increasing extract concentrations (p < 0.05). The shrimp culture industry can utilize paprika extract as a cost-effective, efficient and environmentally friendly immune stimulant at a concentration of 0.5%.

Targeting apoptosis and unfolded protein response: the impact of β-hydroxybutyrate in clear cell renal cell carcinoma under glucose-deprived conditions.

Clear cell renal cell carcinoma (ccRCC) plays a significant role in the mortality associated with kidney cancer. Targeting biological processes that inhibit cancer growth opens up new treatment possibilities. The unfolded protein response (UPR) and apoptosis have crucial roles in RCC progression. This study investigates the impact of β-hydroxybutyrate (BHB) on ccRCC cells under glucose deprivation resembling as a ketogenic diet. Caki-1 ccRCC cells were exposed to decreasing glucose concentrations alone or in combination with 10 or 25mM BHB during 48 and 72h. Cell viability was determined using MTT assay. The mRNA expression level of apoptosis-and UPR-related markers (Bcl-2, Bax, caspase 3, XBP1s, BIP, CHOP, ATF4, and ATF6) were assayed by qRT-PCR. Cell viability experiments demonstrated that combining different doses of BHB with decreasing glucose levels initially improved cell viability after 48h. Nevertheless, this trend reversed after 72h, with higher impacts disclosed at 25mM BHB. Apoptosis was induced in BHB-treated cells as caspase-3 and Bax were increased and Bcl-2 was downregulated. BHB supplementation reduced UPR-related gene expression (XBP1s, BIP, CHOP, ATF4, and ATF6), revealing a possible mechanism by which BHB affects cell survival. This research emphasizes the dual effect of BHB, initially suppressing cell- survival under glucose deprivation but eventually triggering apoptosis and suppressing UPR signaling. These data highlight the intricate connection between metabolic reprogramming and cellular stress response in ccRCC. Further research is recommended to explore the potential of BHB as a therapeutic strategy for managing ccRCC.

The inflammatory injury of porcine small intestinal epithelial cells induced by deoxynivalenol is related to the decrease in glucose transport.

The present study aimed to investigate the effects of deoxynivalenol (DON) stimulation on inflammatory injury and the expression of the glucose transporters sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter protein 2 (GLU2) in porcine small intestinal epithelial cells (IPEC-J2). Additionally, the study aimed to provide initial insights into the connection between the expression of glucose transporters and the inflammatory injury of IPEC-J2 cells. DON concentration and DON treatment time were determined using the CCK‑8 assay. Accordingly, 1.0 µg/mL DON and treatment for 24h were chosen for subsequent experiments. Then IPEC-J2 cells were treated without DON (CON, N = 6) or with 1 μg/mL DON (DON, N = 6). Lactate dehydrogenase (LDH) content, apoptosis rate, and proinflammatory cytokines including interleukin (IL)-1β, Il-6, and tumor necrosis factor α (TNF-α) were measured. Additionally, the expression of AMP-activated protein kinase α1 (AMPK-α1), the content of glucose, intestinal alkaline phosphatase (AKP), and sodium/potassium-transporting adenosine triphosphatase (Na+/K+-ATPase) activity, and the expression of SGLT1 and GLU2 of IPEC-J2 cells were also analyzed. The results showed that DON exposure significantly increased LDH release and apoptosis rate of IPEC-J2 cells. Stimulation with DON resulted in significant cellular inflammatory damage, as evidenced by a significant increase in proinflammatory cytokines (IL-1β, IL-6, and TNF-α). Additionally, DON caused damage to the glucose absorption capacity of IPEC-J2 cells, indicated by decreased levels of glucose content, AKP activity, Na+/K+-ATPase activity, AMPK-α1 protein expression, and SGLT1 expression. Correlation analysis revealed that glucose absorption capacity was negatively correlated with cell inflammatory cytokines. Based on the findings of this study, it can be preliminarily concluded that the cell inflammatory damage caused by DON may be associated with decreased glucose absorption.