Glutamic Pyruvic Transaminase Research Articles

The prognostic value of cartilage intermediate layer protein 1 (CILP1) in patients with diabetic cardiomyopathy.

To measure the plasma levels of human cartilage intermediate layer protein 1 (CILP1) in patients with diabetic cardiomyopathy (DCM), and to investigate its association with the occurrence of major adverse cardiovascular events (MACE) in DCM. A total of 336 diabetic patients were enrolled and assigned into two groups based on the presence or absence of DCM (DCM group and N-DCM group). The baseline clinical data including glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic acid transferase (AST), albumin, serum creatinine, glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), and N-terminal pro brain natriuretic peptide (NT-proBNP) were recorded. Subsequently, plasma levels of CILP1 at admission were detected by the enzyme linked immunosorbent assay (ELISA) method. Echocardiographic parameters were also acquired for all patients. The association of CILP1 with LVEF, LVDD and CRP was determined. In addition, the occurrence of MACE was examined during the 12-month follow-up in the DCM group. The concentration of CILP1 in the DCM group was higher than in the N-DCM group [1329.97 (1157.14, 1494.36) ng/L vs. 789.00 (665.75, 937.06) ng/L, P < 0.05], higher in the MACE group than in the non-MACE group [1777.23 (1532.83, 2341.26)ng/L vs. 885.00 (722.40, 1224.91) ng/L, P < 0.05). Correlation analysis revealed that CILP1 expression was associated with LVEF, CRP and LVDD (r = -0.58, 0.29 and 0.44, respectively, P < 0.05). Analysis of a nomogram demonstrated that CILP1, sex, age, BMI, LVEF and LVDD could predict the occurrence of MACE in DCM patients at 12months (P < 0.05). The plasma levels of CILP1 were independently associated with a stronger discriminating power for DCM. Furthermore, inclusion of CILP1 as a covariate in the model caused a significant improvement in risk estimation compared with traditional risk factors for DCM [BASIC: AUC: 0.556, 95%CI: 0.501-0.610; BASIC + CILP1: AUC: 0.913, 95%CI: 0.877-0.941, P < 0.05] and MACE [BASIC: AUC: 0.710, 95%CI: 0.616-0.792; BASIC + CILP1: AUC: 0.871, 95%CI: 0.794-0.928, P < 0.05]. The serum concentration of CILP1 was increased in DCM patients. Elevated fasting plasma CILP1 levels was a robust diagnostic marker of DCM and was independently associated with an increased risk of MACE.

Cold-Pressed Aristotelia chilensis (Mol.) Stuntz Seed Oil Prevents Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD) in a High-Fat-Diet-Induced Obesity Murine Model

This study evaluated the effects of cold-pressed maqui (Aristotelia chilensis (Mol.) Stuntz) seed oil (MO) on liver metabolism and biochemical markers in a high-fat diet (HFD) murine model. In it, the fatty acid profile, tocopherol and tocotrienol contents, and antioxidant capacity of MO were analyzed. Male C57BL/6 mice were divided into four groups (i.e., a, b, c, and d groups) and supplemented for 12 weeks according to the following distribution: (a) control diet (CD)-sunflower oil (SO), (b) CD+MO, (c) HFD+SO, and (d) HFD+MO. Total body and organ weights, serum markers, and liver fat infiltration were assessed. MO contained 32.31% oleic acid, 46.41% linoleic acid, and 10.83% α-linolenic acid; additionally, α- and γ-tocopherol levels were 339.09 ± 5.15 and 135.52 ± 38.03 mg/kg, respectively, while β-, δ-tocopherol, and α-tocotrienol were present in trace amounts and the antioxidant capacity measured was 6.66 ± 0.19 μmol Trolox equivalent/g. MO supplementation significantly reduced the visceral fat (0.76 ± 0.06 g vs. 1.32 ± 0.04 g) and GPT (glutamate pyruvate transaminase) levels (71.8 ± 5.0 vs. 35.2 ± 2.6 U/L), and the liver fat infiltration score (6 vs. 3) in the HFD+MO group compared to HFD+SO. It is suggested that MO may effectively prevent fatty liver disease, warranting further research on its potential benefits for human health.

Hepatoprotective Effect of Padina gymnospora in Albino Wistar Rat; A Biochemical and Histopathological Studies

The methanolic extract of brown algae, Padina gymnospora (PG) was tested for hepatoprotective properties against paracetamol (acetaminophen, APAP)-induced liver damage in male albino Wistar rat through in-vitro model. Liver is damaged by the variation of serum enzymatic and biochemical markers, such as serum glutamate oxaloacetate transaminase (SGOT or AST), serum glutamate pyruvate transaminase (SGPT or ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), bilirubin, albumin, and lipid peroxidation and antioxidant status were measured by SOD and SDH. The study found that PG caused dose-dependent histopathological changes in the liver and kidney of the rats. While low doses caused minimal alterations, higher doses resulted in significant tissue damage. This suggests that, despite its therapeutic potential, careful consideration is needed regarding dosage to ensure safety. Acute toxicity studies revealed that the LD50 value exceeded 3 g/kg body weight. These results indicate that the methanolic extract of PG contains active compounds with antioxidant, anti-inflammatory, detoxification support, liver regeneration, cholesterol regulation, prevention of liver fibrosis and hepatoprotective effects against high doses of paracetamol-induced hepatotoxicity [Fig. 1].

Comparative Transcriptome Analysis Reveals the Impact of a High-Fat Diet on Hepatic Metabolic Function in Tilapia (Oreochromis niloticus)

Hepatic steatosis is prevalent among cultured fish, yet the molecular mechanisms remain incompletely understood. This study aimed to assess changes in hepatic metabolic function in tilapia and to explore the underlying molecular mechanisms through transcriptomic analyses. Tilapia were allocated into two groups: a normal control (Ctr)-fed group and a high-fat diet (HFD)-fed group. Serum biochemical analyses revealed that HFD feeding led to liver damage and lipid accumulation, characterized by elevated levels of glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), triglycerides (TGs), and total cholesterol (TC). Transcriptome analysis showed that 538 genes were significantly downregulated, and 460 genes were significantly upregulated in the HFD-fed fish. Gene Ontology (GO) enrichment analysis showed that these differentially expressed genes (DEGs) were apparently involved in the lipid metabolic process and monocarboxylic acid metabolic process. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated significant alterations in pathways of steroid biosynthesis, porphyrin metabolism, terpenoid backbone biosynthesis, and retinol metabolism after HFD feeding. Additionally, results from Gene Set Enrichment Analysis (GSEA) revealed that gene expression patterns in pathways including oxidative phosphorylation, protein export, protein processing in the endoplasmic reticulum, and ribosome biogenesis were positively enriched in the HFD-fed tilapia. These findings provide novel insights into the mechanisms underlying HFD-induced hepatic dysfunction in fish, contributing to the optimization of feeding strategies in aquaculture.

The influence of the combination of methanolic extract Scurrula atropurpurea (Blume) and Dendrophthoe pentandra on rat liver function and structure

Background. Tea mistletoe (Scurrula atropurpurea (Blume)) and mango mistletoe (Dendrophthoe pentandra) have been known as a potential medicine for several diseases.Objective: to investigate the effect of the combination of methanolic extract Scurrula atropurpurea (Blume) and Dendrophthoe pentandra (MESA-DP) on rat liver function and structure using serological and histopathological analysis.Material and methods. This study was experimental during 28 days using 20 rats divided into four groups (Group 1 as a control, while Groups 2, 3, and 4 were given MESA-DP at doses 250, 500, and 1,000 mg/kg of body weight, respectively). The liver histopathological structure was observed using hematoxylin-eosin staining. The liver function assessment included total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), total protein, albumin, globulin, cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels. Data were analyzed using a one-way ANOVA analysis (ANalysis Of VAriance) and performed via SPSS Statistics 17.0 (IBM, USA).Results. The administration of MESA-DP did not show significant differences at all doses for the liver rat function in total bilirubin, SGOT, SGPT, albumin, cholesterol and triglycerides (p&gt;0.05), while globulin, total protein, HDL and LDL showed significant results (p&lt;0.05). The liver histopathological structure showed the number of pyknotic, karyorrhectic and karyolytic cells in rats after MESA-DP administration compared to controls, which grew with increasing dose.Conclusion. The liver function in rats after being exposed to MESA-DP was not affected in terms of total bilirubin, SGOT, SGPT, albumin, cholesterol, and triglyceride levels. However, using MESA-DP increased the necrotic liver cells. It may be beneficial for the liver health of experimental animals taking into account the correct dosage.

Efficacy of Cytoreg in the treatment of diabetic foot disease.

Complications from diabetic foot wounds, including bacterial infection, ulceration and gangrene, are major causes of hospitalisation and are responsible for 85% of amputations in patients with diabetes. Given that orally administered investigational therapeutic Cytoreg (Cytorex de Venezuela SA, Venezuela), a defined aqueous mixture of hydrofluoric, hydrochloric, sulfuric, phosphoric, citric and oxalic acids, has been shown to increase levels of arterial blood oxygen in a Wistar rat model, oral and oral+topical Cytoreg were tested on patients with diabetic foot ulcers (DFUs) under a humanitarian, compassionate-use protocol. All patients received oral Cytoreg (5.0 ml concentrate in fruit juice) for 30 days; half also received weekly wound washing with Cytoreg concentrate in isotonic saline (1:50 volume/volume) (oral+topical group). In addition to standard clinical observations, wounds were monitored against the Saint Elian checklist system for the diabetic foot. A total of 10 patients took part in the study. Complete wound closure was observed in 4/5 patients in the oral+topical group; in the remaining patient, necrotic and fibrin tissues on the wound edges were eliminated. Half (2/4) of the patients receiving oral-only Cytoreg experienced complete wound closure; one patient in this group was removed prematurely because of an unrelated illness and was not replaced. During the study, no significant differences were observed between groups in either the oxygen saturation of the affected tissues or in insulin and glycaemia levels (p<0.05). Significant increases in arterial haemoglobin and arterial oxygen partial pressure (p<0.05) were observed, and significant decreases were measured in the levels of glycosylated haemoglobin, aspartate aminotransferase, glutamic-pyruvic transaminase, creatine and urea (p<0.05). The results of this study justify an expanded clinical study for the treatment of DFUs with Cytoreg.

The Ku70-SIX1-GPT2 axis regulates alpha-ketoglutarate metabolism to drive progression of prostate cancer.

Sine oculis homeobox homolog 1 (SIX1) is a new identified cancer driver in the development of prostate cancer (PC). However, the upstream regulatory mechanisms for SIX1 reactivation in cancer remains elusive. Here, we found that Ku70 robustly interacts with SIX1 in the nucleus of PC cells. The HD domain of SIX1 and the DBD domain of Ku70 are required for formation of Ku70-SIX1 complex. 20 groups of hydrogen bonds were identified in this complex by molecular dynamics simulation. Depletion of Ku70/SIX1 notably abrogates the proliferation and migration of PC. Further studies revealed that SIX1 is recruited to the promoter region on glutamate-pyruvate transaminase 2 (GPT2). Ku70 enhances the SIX1-mediated transcriptional activation on GPT2, thereby facilitating the generation of alpha-ketoglutarate (α-KG). In addition, formation of the Ku70-SIX1 complex promotes GPT2-dependent cell proliferation and migration in PC. Moreover, the expression of GPT2 is upregulated and strongly correlated with the expression of Ku70/SIX1 in PC tissues. In summary, our findings not only provide insight into the mechanistic interactions between Ku70 and SIX1, but also highlight the significance of the Ku70-SIX1-GPT2 axis for α-KG metabolism and PC carcinogenesis.

Histological and Biochemical Evaluation of Silibinin in Treatment of Periodontitis Induced in Rats with Liver Cirrhosis.

This study aimed to evaluate the impact of silibinin as a therapeutic agent on ligature-induced periodontitis in rats with liver cirrhosis. Twenty-five Wistar rats were enrolled in this study. Group A (Control) included eight rats. The other 17 rats received CCl4 to develop cirrhosis, which was confirmed by sacrificing one of the rats and performing a histological examination of its liver tissue. Periodontitis was induced in the remaining 16 rats then they were allocated into (n = 8) group B-periodontitis with cirrhosis and group C-silibinin-treated group, 5 times/week starting from week 11 till week 14. Animals of the three groups were euthanized, and biochemical analysis comprising of liver functions assessment (serum levels of glutamate-pyruvate transaminase, serum levels of glutamate-oxalate transaminase, TIMP1) and oxidative stress index [MDA, nitric oxide (NO), superoxide dismutase (SOD), and catalase (CAT)] and histological examination were conducted by the end of week 14. Group C revealed a more organized orientation of the periodontal ligament (PDL) collagen fibers with a marked regain of the alveolar bone height compared to group B. Biochemical analysis confirmed the potent therapeutic effect of silibinin manifested by a significant improvement in the biochemical parameters: tissue inhibitor of metalloproteinase-1, MDA, NO levels, and antioxidant enzymes. Group B was associated with the most unfavorable biochemical findings and the maximum periodontal destruction. Group C demonstrated a positive osteogenic capacity and a noteworthy improvement in biochemical findings, which were comparable to those of group A, which displayed normal and healthy findings. The study highlights the potential use of silibinin as a natural remedy with minimal side effects for treating periodontitis in rats with liver cirrhosis. The findings could be translated to human clinical trials, which may lead to new treatment strategies using silibinin as a targeted therapy or as adjunctive therapy to conventional periodontal treatment for patients with liver cirrhosis who are more susceptible to periodontitis. How to cite this article: Shawky HA, Ahmed NM, Essawy MM, et al. Histological and Biochemical Evaluation of Silibinin in Treatment of Periodontitis Induced in Rats with Liver Cirrhosis. J Contemp Dent Pract 2024;25(7):631-638.

Acute Febrile Illness in India: An Epidemiological Retrospective Study.

Acute febrile illness (AFI) is a frequent occurrence in India, often complicated by a multitude of pathogenic and etiological factors. In this context, it is important to analyze the biochemical, hematological, and epidemiological clinical parameters of AFI patients in the North Indian population. This study included 1,819 patients of various ages who presented with new-onset acute febrile illness (AFI) between 2017 and 2021. Among these patients, 211, with a median age of 40 years (ranging from 2 to 85 years), were selected for further analysis. At enrollment, clinical examination involved collecting respiratory tract specimens, blood, and urine samples for bio-chemical analysis, with subsequent data analysis conducted using statistical methods. The following biochemical parameters were analyzed: C-reactive protein (CRP), alkaline phosphatase (ALP), serum glutamate-pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transpeptidase (GGT), and total protein serum. The hematological parameters included total leukocyte count (TLC), lymphocyte count, monocyte count, eosinophil count, red blood cell count (RBCs), packed cell volume (PCV), erythrocyte sedimentation rate (ESR), hematocrit value, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Additionally, clinical parameters such as phosphorus, urea, calcium, sodium, uric acid, bilirubin, and potassium were measured. Specific values observed were: SGPT (~113 IU/L in 2018), SGOT (~81 U/L in 2019), GGT (~148 g/L in 2018), and total protein serum (~7 g/L in 2020). The hematological parameters (TLC, lymphocyte, monocyte, RBCs, PCV, ESR, MCV, and MCH). The regression analysis was conducted to explore the temperature recorded at the time of admission, the duration of hospital stays, and biochemical as well as hematological variables of patients suffering from AFI. Karl-Pearson's correlation coefficient and variance inflation factor for each variable mentioned above. Biochemical and hematological parameters were analyzed over different years of intake in patients with Acute Febrile Illness (AFI). Further investigation is required to explore the mechanistic pathways of infection, and preventive measures will be implemented using natural products and other therapeutic interventions. Our data will offer the first systematic assessment of the etiological factors, along with regression analysis and the Karl-Pearson correlation coefficient for each variable in AFI patients.

Enhanced Antidiabetic Effects of Gymnema sylvestre and Probiotics in Alloxan-Induced Diabetic Rats

Abstract Introduction/Objective Introduction: Gymnema sylvestre is a well-known herbal remedy for diabetes, with its anti-diabetic properties attributed to gymnemic acids isolated from its leaves. Probiotics, such as Lactobacillus acidophilus and Lactobacillus casei, have also shown potential in managing diabetes. This study aims to evaluate the combined antidiabetic effects of G. sylvestre and probiotics in alloxan-induced diabetic rats. Methods/Case Report Methods: Experimental rats were divided into seven groups: negative control, untreated diabetic control, L. acidophilus-treated, L. casei-treated, G. sylvestre-treated, a combination of L. casei and G. sylvestre-treated, and a combination of L. acidophilus and G. sylvestre-treated. Blood glucose levels, lipid profiles, and reduced glutathione levels were measured, and histopathological examination of pancreas and kidney tissues was performed. Results (if a Case Study enter NA) Results: In the third week of the experiment, the combined administration of G. sylvestre and probiotics showed the most significant reductions in glucose levels (250 mg/dL), alkaline phosphatase (ALP) (613.3 U/L), urea (31 U/L), serum creatinine (0.77 U/L), and superoxide dismutase (SOD) (854.7 UMOL). G. sylvestre alone exhibited the lowest levels of glutamate pyruvate transaminase (GPT) (30 U/L), cholesterol (41 mg/dL), triglycerides (101.3 mg/dL), very-low-density lipoprotein (VLDL) (22.9 mg/dL), and malondialdehyde (MDA) (119.3 U MOL/SEC). Probiotic treatment alone resulted in the lowest levels of uric acid (UA) (4.4 U/L) and low-density lipoprotein (LDL) (95.06 mg/dL). G. sylvestre demonstrated the highest level of high-density lipoprotein (HDL) (44 mg/dL), while probiotics exhibited the highest catalase (CAT) activity (92 UMOL/SEC). Histopathological examination revealed the preservation of normal pancreatic and renal tissue morphology with G. sylvestre treatment. Conclusion Conclusion: The combination of G. sylvestre and probiotics enhances the antidiabetic activity compared to G. sylvestre alone in alloxan-induced diabetic rats. These findings suggest a potential synergistic effect of combining herbal and probiotic therapy for diabetes management.

Fibroblast growth factor 1 (FGF1) improves glucose homeostasis, modulates gut microbial composition, and reduces inflammatory responses in rainbow trout (Oncorhynchus mykiss) fed a high-fat diet

High-fat diets (HFDs) are widely used in aquaculture due to their lipid and protein-conserving effects, thereby reducing feed costs. However, prolonged feeding of HFD often leads to metabolic disorders in fish, such as disruption of hepatic lipid homeostasis, liver injury, and disruption of glucose homeostasis. Fibroblast growth factor 1 (FGF1) plays an essential role in controlling glucose levels in the body and dampening immune reactions. However, its impact on teleosts remains poorly researched. The therapeutic potential of recombinant FGF1 (rFGF1) was examined in a 6-week culture experiment involving rainbow trout (Oncorhynchus mykiss) that were fed an HFD. The results revealed that rFGF1 significantly reduced serum glucose levels and hepatic PEPCK and G6PC activities, but improved hepatic glycogen (P < 0.05), compared to the HFD + PBS group. Further experiments indicated that the inhibitory effect of rFGF1 on hepatic gluconeogenesis was mediated by the cAMP signaling pathway and was dependent on the high expression of PDE4D. In addition, rFGF1 increased hepatic glycogen content, which involves the AKT-GSK3β axis. Despite this increase, rFGF1 did not lead to glycogen storage disease, as shown by reduced hepatic inflammation as a result of decreased GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), and elevated SOD (superoxide dismutase) in the rFGF1-treated group, accompanied by decreased il-1β, il-6, and xbp-1, and elevated nrf2 and number of hepatocyte autophagosomes. Alterations in gut microbes and short-chain fatty acids (SCFAs) were noted, indicating that rFGF1 caused a notable rise in intestinal Lactobacillus, acetic acid, and butyric acid levels. This study investigated the molecular mechanisms of rFGF1 on glucose metabolism and inflammatory responses in an HFD-fed rainbow trout model, providing new insights to improve the regulation of glucose metabolism in carnivorous fish.

“Copper-loaded microplastics unleash endoplasmic reticulum stress-driven liver apoptosis in fish Channa punctatus”

The extensive use of plastics has led to significant microplastic pollution, posing threats to environmental and human health. Concerns are growing about the toxicity of microplastics (MPs) and their ability to adsorb contaminants like Copper (Cu2+). Therefore, this study investigated the effects of environmentally realistic concentrations of Polyvinyl Chloride (PVC)-MPs and Copper, both individually and together, with a particular focus on triggering Endoplasmic reticulum (ER) stress-driven apoptosis in the liver of Channa punctatus. Well-habituated fish were organized into four groups: Group I (Control), Group II (0.5 mg/L PVC-MPs), Group III (0.85 mg/L Copper), and Group IV (0.5 mg/L PVC-MPs + 0.85 mg/L Copper). The treatment period was 15, 30, 45 and 60 days. Various liver parameters were assessed according to standard protocols to understand the repercussions of intoxication. A significant (p < 0.05) increment in Reactive Oxygen Species (ROS) pointed to a substantial rise in oxidative stress. Enzymatic antioxidants like superoxide dismutase (SOD) and catalase (CAT) showed significantly (p < 0.05) elevated extents while reduced glutathione (GSH) levels significantly (p < 0.05) dropped in a duration-dependent pattern. Additionally, lipid peroxidation (LPO) activities surged significantly (p < 0.05), and notable hepato-structural disruptions were observed. The evidence of liver damage was further verified by a significant (p < 0.05) rise in concentrations of hepatic biomarkers viz. Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamic Pyruvic Transaminase (SGPT), and Alkaline phosphatase (ALP). Moreover, ER-stress was validated through the increased intracellular calcium levels along with the heightened expression of grp78, chop, atf4, perk, eIF2α, and gadd34 in exposed groups. This intricate cascade subsequently elicited the activation of bax, caspase-3, caspase-9, and apaf-1, while modulation of bcl-2, thereby driving hepatocyte-apoptosis via ER-stress response in C. punctatus, a widely consumed food-fish. Our findings underscore the toxic threats of Copper-laden PVC-MPs to aquatic life and potentially the broader ecosystem.

Comparative study of immune responses and intestinal microbiota in the gut-liver axis between wild and farmed pike perch (Sander Lucioperca).

Pike perch (Sander Lucioperca) is a predatory freshwater fish, which is highly popular amongst consumers, owing to its white flesh with a delicate structure and mild flavor. Compared to wild pike perch, the diet of farmed ones has shifted from natural food to artificial feeds. These changes would affect the gut flora of the pike perch. Endogenous metabolites of the intestinal flora are transferred through the gut-liver axis, which affects the physiological functions of the host. By studying wild and farmed individuals of the pike perch, novel insights into the stability of the intestinal flora can be provided. In this study, we measured various immune parameters in the blood, liver and intestine of wild and farmed pike perch using enzyme activity assays and real-time fluorescence quantitative PCR. Gut microbes were also collected for 16S rRNA gene sequencing. Our results showed that the serum low-density lipoprotein cholesterol (LDL-C) levels were twice as high in the wild group as in the farmed group. Furthermore, the activities of glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) in the intestinal tissues of the wild group were 733.91 U/g and 375.35 U/g, which were significantly higher than those of the farmed group. Expression of IL10 in the liver of farmed pike perch was also 4-fold higher than that of wild pike perch. The expression of genes related to the p53-BAX/Bcl2 signaling pathway was higher in both intestinal and liver tissues of wild pike perch compared with farmed. 16S rRNA gene analysis of the gut microflora showed a high relative abundance of Cetobacterium in the gut of farmed pike perch. As a result, our study indicates that dietary differences affect the diversity, composition and relative abundance of the gut flora of the pike perch. Meanwhile, it affects the glycolipid metabolism and immunomodulation of pike perch.

12614 Induction Of Gpt2 During Metabolic Stress Is Associated With Reduced Incretin Responsiveness And Decreased β-cell Resilience To Metabolic Stress

Abstract Disclosure: S. Sen: None. A.V. Rozo: None. M. Haemmerle: None. J. Roman: None. A.V. Scota: None. J.A. Christine: None. E.M. Morrow: None. S.A. Tersey: None. C.B. Newgard: None. N.M. Doliba: None. D.A. Stoffers: None. Elevated blood glucose and lipids compromise pancreatic β-cell survival and function, but the underlying molecular mechanisms are ill-understood. We previously found that mitochondrial glutamate-pyruvate transaminase 2 (GPT2) is induced by ER and glucolipotoxic (GLT) stress. Here, we find that islets from type 2 diabetic donors exhibited markedly elevated levels of GPT2 compared to those of non-diabetic donors. GLT stress induced GPT2 in MIN6 cells, primary murine, and human non-diabetic islets. We generated β-cell specific Gpt2-deficient (Gpt2βKO) and Gpt2 floxed control (Gpt2f/f) mice to study the in vivo role of Gpt2 in β-cells. Intraperitoneal (IP) glucose tolerance (GTT) of Gpt2βKO mice was minimally affected on chow diet; therefore, we placed Gpt2f/f and Gpt2βKO mice on 45 kcal% high-fat and matched control diets. At 1 week, HFD-fed Gpt2βKO mice exhibited reduced β-cell death, measured by droplet digital PCR of circulating unmethylated preproinsulin DNA and by TUNEL analysis. Over 37 weeks, HFD-fed Gpt2βKO mice showed lower random blood glucose similar to Gpt2f/f mice under a control diet. While IPGTT was modestly improved in HFD-fed Gpt2βKO compared to HFD-fed Gpt2f/f mice, insulin secretion was not enhanced. Remarkably, oral glucose administration markedly improved glucose tolerance and enhanced insulin secretion of control- and HFD-fed Gpt2βKO mice compared to Gpt2f/f mice, while GLP-1 and GIP levels were unaltered, suggesting enhanced incretin action on the β-cell. Indeed, Gpt2βKO mice (under both control and high-fat diets) were more responsive to administration of GLP1R agonist Exendin-4 (Ex4) than Gpt2f/f mice. Isolated Gpt2βKO islets secreted more insulin when stimulated by Ex4 and GIP but not acetylcholine. Perifusion assay revealed markedly enhanced insulin secretion of Gpt2βKO islets in response to a stepwise exposure to increasing Ex4 doses, indicating enhanced incretin sensitivity. Metabolic flux analysis of Gpt2βKO and Gpt2f/f islets exposed to uniformly labeled glucose (U-13C glucose) under low (2.8mM), high (12mM) glucose, and high glucose with Ex4 conditions revealed elevated levels of key TCA cycle intermediates in Gpt2βKO islets under high glucose and high glucose+Ex4 conditions, indicating increased TCA cycle flux that likely enhances insulin secretion. Gpt2βKO mice had higher β cell mass than Gpt2f/f littermates under control diet and HFD feeding. Bulk islet RNA-seq from Gpt2f/f and Gpt2βKO mice exposed to GLT revealed upregulation of genes responsible for cell cycle and division pathways and downregulation of apoptosis and ER stress genes, consistent with enhanced survival of Gpt2βKO islets under stress conditions. In summary, β-cell GPT2 is increased during metabolic stress and T2D. Its deficiency induces a metabolic reprogramming that improves incretin sensitivity and protects pancreatic β-cells from metabolic stress. Presentation: 6/2/2024

Profil Kadar Enzim Serum Glutamat Piruvat Transaminase (SGPT) dan Serum Glutamat Oksaloasetat Transaminase (SGOT) Mencit Model Diabetes Melitus Pasca Pemberian Ekstrak Kulit Batang Cinnamomum burmanii

Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia. Prolonged hyperglycemia leads to oxidative stress, which plays a crucial role in causing further complications, including liver damage characterized by increased levels of Serum Glutamate Pyruvate Transaminase (SGPT) and Serum Glutamate Oxaloacetate Transaminase (SGOT). This study aimed to examine the effects of Cinnamomum burmanii bark extract on SGPT and SGOT levels in a mouse model of diabetes mellitus. The research employed an experimental design using a completely randomized design. It consisted of five treatment groups: K- (normal mice), K+ (diabetic mice), P1, P2, and P3 (diabetic mice treated with Cinnamomum burmanii bark extract at doses of 125, 250, and 500 mg/kg BW). Streptozotocin was injected into groups K+, P1, P2, and P3 at a dose of 0.1 ml per mouse for 14 days. If blood glucose levels increased, extracts were administered to groups P1, P2, and P3 according to the predetermined doses for 14 days. On day 28, surgery was performed to collect blood serum for SGPT and SGOT analysis.. The results of the study indicated that Cinnamomum burmanii bark extract could reduce SGPT and SGOT levels in the diabetic mouse model. This demonstrates the potential of Cinnamomum burmanii as a therapeutic agent that may help reduce liver damage often observed in diabetes mellitus

Protective effects of dietary protein against nitrite stress in grass carp (Ctenopharyngodon idella): A new perspective

Protein constitutes the predominant essential nutrient in fish feed. Despite extensive research efforts on the dietary protein of fish, limited attention has focused on its potential antistress properties. Therefore, this study sought to examine the impact of dietary protein on the liver structure of grass carp (Ctenopharyngodon idella) and its underlying molecular mechanism after nitrite stress, with the objective of elucidating the role of dietary protein in the stress response of fish. Specifically, various levels of dietary protein (16 %, 19 %, 22 %, 25 %, 28 % and 31 %) were investigated for their effects on liver tissue damage, oxidative stress, endoplasmic reticulum (ER) stress, autophagy and apoptosis in grass carp after exposure to a nitrite solution at a concentration of 10 mg/L for a duration of 96 h.Our study revealed that exposure to nitrite solution resulted in liver structural damage in grass carp. However, 22–25 % dietary protein levels might attenuate the impact of nitrite stress by decreasing liver contents of nitric oxide (NO), peroxynitrite anion (ONOO-), reactive oxygen species (ROS), protein carbonyl (PC), and malondialdehyde (MDA), which is reflected in serum activities of glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT). Histological analysis further supported the protective role of appropriate protein levels (22–28 %) in alleviating nitrite-induced liver tissue damage. Subsequent investigations demonstrated that optimal dietary protein levels decreased ER stress and autophagy in fish by modulating the expression of gene and protein involved in 78 kDa glucose regulated protein (GRP78) pathway and autophagosome formation process, respectively. Meanwhile, appropriate dietary protein levels decreased the activities of caspase-3, caspase-8 and caspase-9 by inhibiting both death receptor pathway and mitochondrial pathway associated with apoptosis. Finally, based on regression analysis of liver ONOO− content, the dietary protein requirement for grass carp (721–1381 g) under nitrite stress was determined to be 25.07 %. Overall, this study provides novel evidence that optimal protein levels can enhance the resistance of grass carp to nitrite stress and mitigate liver tissue damage by reducing oxidative stress cascade damage.

Role of Prophylactic N-Acetylcysteine Supplementation on Postoperative Outcomes in Patients Undergoing Elective Double-Valve Replacement (Aortic and Mitral Valve).

The incidence of postoperative liver dysfunction is high in patients undergoing double-valve replacement - mitral and aortic valve replacement (DVR). This study aims to evaluate N-acetylcysteine's free radical scavenging property (NAC) to prevent postoperative liver dysfunction in these patients, thus affecting overall clinical outcomes. A single-center, prospective, randomized, double-blinded interventional study of 60 patients divided into two groups of 30 each. Group N received prophylactic intravenous NAC, and Group C received volume-matched 5% dextrose. Data comprised demographics, liver function tests (LFT), renal function tests (RFT), vasoactive-inotropic scores (VIS) score, and C-reactive protein (CRP) at various time intervals. Postoperative parameters such as ventilation duration, length of stay in ICU (LOS-ICU), length of hospital stay (LOHS), atrial fibrillation (AF), acute kidney injury (AKI) requiring hemodialysis, and mortality were noted. Statistical analysis was performed with the Student's t-test and Chi-square test (SPSS 22 software). All postoperative LFT parameters (total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), and alkaline phosphatase (ALP)) were significantly lower (P < 0.05) at 24, 48, and 72 hours in Group N compared to Group C. RFT and VIS scores were lower in Group N; however, were not statistically significant except for Serum Creatinine at 48 hours (P = 0.0478). Ventilation duration (P = 0.0465) and LOS-ICU (P = 0.0431) were significantly lower in Group N. Other outcomes like AF, LOHS, and mortality were lower in Group N but were not statistically significant. Our study showed that prophylactic administration of NAC in patients undergoing DVR is associated with a reduction in the incidence of postoperative liver dysfunction with a positive impact on postoperative outcomes.

Evaluation of the Hypoglycemic and Hypolipidemic Potential of Extract Fraction of Quercus baloot Griff Seeds in Alloxan-induced Diabetic Mice.

The discovery and development of new phytomedicines can be greatly aided by plants because of their tremendous therapeutic benefits, efficiency, cost-effectiveness, lack of side effects, and cheaper therapies. In this regard, Quercus baloot, generally known as oak, is used in folkloric medicine for treating and preventing various human disorders, including diabetes. For this purpose, the present study aimed to evaluate crude methanolic extract and various fractions of Quercus baloot for antihyperlipidemic and antihyperglycemic potential followed by the analysis of active compounds. The hypoglycemic and hypolipidemic activity was evaluated in Swiss male Albino mice by administering an oral dose of 150-300 mg/kg of Q. baloot extracts in alloxan induced diabetic mice for 14 days. The results revealed that crude methanolic extract at a dose of 300 mg/kg exhibited a significant reduction in the blood glucose level (198.50 ± 1.99 mg/dl) at day 14 and the same treatment significantly increased the body weight (31.26 ± 0.27 g) at day 14 in comparison to the control group. Moreover, the biochemical parameters were investigated which presented an increase in high-density lipids (HDL) (30.33 ± 0.33 mg/dl), whereas low-density lipids (LDL) showed a significant decrease (105.66 ± 0.26 mg/dl). Additionally, triglyceride levels 104.83 ± 0.70 mg/dl, and total cholesterol 185.50 ± 0.76 mg/dl are significantly decreased. In serum biochemical analysis creatinine and hepatic enzyme markers, like serum glutamate pyruvate transaminase (32.00 ± 0.36 U/mg), serum glutamate oxaloacetate transaminase (34.33 ± 0.61 U/mg), and alkaline phosphatase (157.00 ± 0.73 U/mg), were significantly reduced by the crude methanolic extract at a dose of 300 mg/kg as compared to the control group. The antioxidant enzymes like Superoxide dismutase (4.57 ± 0.011), peroxidases dismutase (6.53 ± 0.014, and catalase (8.38 ± 0.014) at a dosage of 300 mg/kg of methanolic extract exhibited a significant increase. The histopathological study of the diabetic heart, liver, and pancreas showed substantial restoration of damaged tissues in the methanolic extract 150 and 300 mg/kg treated group, which supports the effectiveness of Q. baloot seeds. The gas chromatography-mass spectrometry analysis of methanolic extract identified 10 antidiabetic active compounds in the Q. baloot seeds, validating the antihyperglycemic activity. Thus, methanolic crude extract at the doses 150 and 300 mg/kg of Q. baloot showed significant antihyperlipidemic and antihyperglycemic activities, which validate the folkloric utilization of Q. baloot as a remedy in diabetes. In conclusion, the 300 mg/kg methanolic extract of Q. baloot has notable hypoglycemic and hypolipidemic potential, supporting the plant's traditional medicinal usage in the treatment of diabetes and its complications. Further studies are needed for the purification, characterization, and structural clarification of bioactive compounds.

Diosgenin ameliorating non-alcoholic fatty liver disease via Nrf2-mediated regulation of oxidative stress and ferroptosis.

This study aimed to investigate the mechanisms through which diosgenin inhibits the pathogenesis of non-alcoholic fatty liver disease, focusing particularly on ferroptosis-related pathways and its reliance on nuclear factor erythroid 2-related factor 2. Using a rat model, we showed diosgenin's efficacy in reducing lipid deposition throughout the body and examined its impact on ferroptosis-related gene expression in vivo. Moreover, in vitro experiments using human hepatocellular liver carcinoma cell line cells were conducted to assess oxidative stress and ferroptosis levels. Diosgenin decreased lipid accumulation and steatosis; lowered serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, glutamic pyruvic transaminase and glutamic oxaloacetic transaminase; reduced interleukin-1β and tumour necrosis factor-α; diosgenin decreased malondialdehyde levels; and increased serum superoxide dismutase levels in a rat model of high-fat diet-induced non-alcoholic fatty liver disease. Diosgenin upregulated the expression of nuclear factor erythroid 2-related factor 2 and its downstream ferroptosis-related genes to inhibit ferroptosis in the livers of rats with non-alcoholic fatty liver disease. Diosgenin decreased reactive oxygen species levels and enhanced the expression of ferroptosis-related genes in human hepatocellular liver carcinoma cells induced by free fatty acids, with its effects being dependent on nuclear factor erythroid 2-related factor 2. This study highlights the potential of diosgenin from Dioscoreaceae plants in mitigating oxidative stress and ferroptosis levels through nuclear factor erythroid 2-related factor 2 regulation, offering novel insights into the treatment of non-alcoholic fatty liver disease and other metabolic disorders through traditional Chinese medicine.

EFFECTS OF HUMAN CYTOMEGALOVIRUS ON SOME HEMATOLOGICAL PARAMETERS AND LIVER FUNCTION IN PREGNANT WOMEN, YEMEN

Human Cytomegalovirus (HCMV) infection is a common congenital infection that affects approximately 0.7%–1% of all live births worldwide. Approximately 11% of newborns who are infected show symptoms at birth, and of these, between 30% and 40% are at a risk of experiencing long-term neurological complications. This study aimed to evaluate the effect of HCMV on hematological parameters and liver function in pregnant women in Hajjah governorate, Yemen. This study is a cross-section study that conducted in the Hajjah governorate of Yemen during a period of March to June 2023. A total of 108 blood specimens were collected from participants; 78 from patients group and 30 health group. Hematological parameters, such as total red blood cell count (RBC), hemoglobin (HB), platelet count (PLT), and white blood cells (WBC), as well as liver function tests, such as total protein, albumin, alkaline phosphatase (ALP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), total bilirubin, and direct bilirubin, were measured. Majority of participant patients aged between 16–21 years 27 (34.7%), studied at secondary schools (46.2%), in their second trimester 51 (65.4%), those with multigravida 54 (69.2%), and those with no history of congenital diseases 60 (76.9%). Compared with the control group, the mean WBC levels were significantly lower in HCMV patients (P &lt; 0.05), whereas PLT levels were higher among HCMV patients (P &lt; 0.05). Additionally, the mean levels of total bilirubin, direct bilirubin, SGOT, ALP, and albumin were significantly lower in patients with HCMV than in HC (P &lt; 0.05). Furthermore, there were no significant differences between the patient and healthy groups in terms of HB, RBC counts, SGPT, and total protein (P &gt; 0.05). It can be concluded that HCMV infection had a statistically significant effect on WBC, PLT, total bilirubin, direct bilirubin, SGOT, ALP, and albumin levels in pregnant women. Consequently, further studies are needed to define the role of HCMV in liver disorders.