Expression Of Glucose Metabolism-related Genes Research Articles

Transcriptional expression of SLC16A7 as a biomarker of occult lymph node metastases in patients with head and neck squamous cell carcinoma.

Glucose is the main energy substrate of tumor cells. This study aims to assess whether the transcriptional expression of glucose metabolism-related genes is associated with occult lymph node metastases in head and neck squamous cell carcinoma (HNSCC) patients. We examined the transcriptional expression of a panel of glucose metabolism-related genes in a cohort of 53 patients with HNSCC without cervical lymph node involvement at the time of diagnosis (cN0) and subsequently treated with elective neck dissection. Occult lymph node metastases were found in 37.7% (n = 20) of the patients. Among the analyzed genes, SLC16A7 exhibited the strongest association with the presence of occult lymph node metastases. Patients with occult lymph node metastases (cN0/pN +) had significantly lower SLC16A7 expression values (p = 0.001). Patients with low SLC16A7 expression (n = 17, 32.1%) had a frequency of occult lymph node metastases of 76.5%, while for patients with high SLCA16A7 expression (n = 36, 67.9%) it was 19.4% (P = 0.0001). A multivariable analysis showed that patients with low expression of SLC16A7 had a 12.6 times higher risk of developing occult lymph node metastases. cN0 HNSCC patients with low SLC16A7 expression had a higher risk of occult lymph node metastases.

Metabolome and microbiome analyses of the anti-fatigue mechanism of Acanthopanax senticosus leaves.

Acanthopanax senticosus leaves, widely used as a vegetable and tea, are reported to be beneficial in treating neurological disorders. At present, their anti-fatigue effect remains to be established. In this study, we analyzed the composition of the extracts from A. senticosus leaves and confirmed their antioxidant and anti-inflammatory properties at the cellular level. In mice subjected to exhaustive running on a treadmill, supplementation with A. senticosus leaf extracts enhanced exercise performance and alleviated fatigue via the reversal of exercise-induced 5-HT elevation, metabolic waste accumulation, organ damage, and glucose metabolism-related gene expression. The collective findings from microbiome and metabolomic analyses indicate that A. senticosus leaf extracts increase α-diversity, regulate microbial composition, and reverse exercise-mediated disruption of carbohydrate, creatine, amino acid, and trimethylamine metabolism. This study provides preliminary evidence for the utility of A. senticosus leaves as a promising anti-fatigue food and offers insights into the underlying mechanism.

Ferroptosis-related gene glutathione peroxidase 4 promotes reprogramming of glucose metabolism via Akt-mTOR axis in intrahepatic cholangiocarcinoma.

The role of the ferroptosis-related gene glutathione peroxidase 4 (GPX4) in oncology has been extensively investigated. However, the clinical implications of GPX4 in patients with intrahepatic cholangiocarcinoma (ICC) remain unknown. This study aimed to evaluate the prognostic impact of GPX4 and its underlying molecular mechanisms in patients with ICC. Fifty-seven patients who underwent surgical resection for ICC between 2010 and 2017 were retrospectively analyzed. Based on the immunohistochemistry, patients were divided into GPX4 high (n = 15) and low (n = 42) groups, and clinical outcomes were assessed. Furthermore, the roles of GPX4 in cell proliferation, migration and gene expression were analyzed in ICC cell lines in vitro and in vivo. The results from clinical study showed that GPX4 high group showed significant associations with high SUVmax on 18F-fluorodeoxyglucose-positron emission tomography (≥8.0, P = 0.017), multiple tumors (P = 0.004), and showed glucose transporter 1 (GLUT1) high expression with a trend toward significance (P = 0.053). Overall and recurrence-free survival in the GPX4 high expression group were significantly worse than those in the GPX4 low expression group (P = 0.038 and P < 0.001, respectively). In the experimental study, inhibition of GPX4 attenuated cell proliferation and migration in ICC cell lines. Inhibition of GPX4 also decreased the expression of glucose metabolism-related genes, such as GLUT1 or HIF1α. Mechanistically, these molecular changes are regulated in Akt-mechanistic targets of rapamycin axis. In conclusion, this study suggested the pivotal value of GPX4 serving as a prognostic marker for patients with ICC. Furthermore, GPX4 can mediate glucose metabolism of ICC.

Haloxyfop-P-methyl induces immunotoxicity and glucose metabolism disorders and affects the Nrf2/ARE pathway mediated antioxidant system in Chiromantes dehaani

Haloxyfop-P-methyl is used extensively in agricultural production, and its metabolites in soil have potentially toxic effects on aquatic ecosystems. In this study, we explored the toxicity of haloxyfop-P-methyl on Chiromantes dehaani. The results of the 21-day toxicity test showed that haloxyfop-P-methyl decreased the weight gain (WG), specific growth rate (SGR) and hepatosomatic index (HSI). In glucose metabolism, haloxyfop-P-methyl reduced pyruvate, lactate, lactate dehydrogenase and succinate dehydrogenase, but enhanced glucose-6-phosphate dehydrogenase and hexokinase. Furthermore, expression of glucose metabolism-related genes was upregulated. We cloned the full-length CdG6PDH gene, which contains a 1587 bp ORF that encoded a 528 amino acid polypeptide. In antioxidant system, haloxyfop-P-methyl increased glutathione, thioredoxin reductase and thioredoxin peroxidase activities and activated the Nrf2/ARE pathway through upregulation of ERK, JNK, PKC and Nrf2. In immunity, low concentrations haloxyfop-P-methyl, or short-term exposure, upregulated the expression of immune-related genes and enhanced immune-related enzymes activity, while high concentrations or long-term exposure inhibited immune function. In summary, haloxyfop-P-methyl inhibited the growth performance, disrupted glucose metabolism, activated the antioxidant system, and led to immunotoxicity. The results deepen our understanding of the toxicity mechanism of haloxyfop-P-methyl and provide basic biological data for the comprehensive assessment of the risk of haloxyfop-P-methyl to the environment and humans.

Delayed feeding of a high-sucrose diet led to increased body weight by affecting the circadian rhythm of body temperature and hepatic lipid-metabolism genes in rats

Skipping breakfast is an irregular feeding behavior, typically in young people. In our previous study, we established a 4 h-delayed feeding protocol for rats as a breakfast-skipping model and showed that the 4 h-delayed feeding of a high-fat diet led to body weight gain in rats. Excess sucrose induces metabolic syndrome and fatty liver. Recently, excess sucrose intake has received increased attention. Young people generally consume more sugar than adults do. In the present study, we investigated whether a 4 h-delayed feeding promoted high-sucrose diet-induced abnormalities in lipid metabolism, such as fatty liver and obesity in rats. The 4 h-delayed feeding rats showed increased body weight gain, although it did not induce fatty liver and hyperlipidemia compared to normal feeding rats. Serum insulin concentration during the feeding period was higher than in the control rats, suggesting that slight insulin resistance was induced by the 4 h-delayed feeding. The surge in body temperature was also delayed by 4 h in response to the 4 h-delayed feeding. This delay would result in less energy expenditure to increase body weight. The oscillations of hepatic lipid and glucose metabolism-related gene expression were delayed by almost 2–4 h, and the clock genes were delayed by approximately 2 h. The 4 h-delayed feeding induced weight gain by affecting body temperature, insulin resistance, and circadian oscillation of lipid metabolism-related genes in rats fed a high-sucrose diet, suggesting that a high sucrose intake with breakfast skipping leads to obesity.

Effect of polystyrene nanoplastics on cell apoptosis, glucose metabolism, and antibacterial immunity of Eriocheir sinensis

The adverse effects of plastic waste and nanoplastics on the water environment have become a focus of global attention in recent years. In the present study, using adult Chinese mitten crabs (Eriocheir sinensis) as an animal model, the bioaccumulation and the in vivo and in vitro toxicity of polystyrene nanoplastics (PS NPs), alone or in combination with the bacteria, were investigated. This study aimed to investigate the effects of PS NPs on apoptosis and glucose metabolism in Chinese mitten crabs, and whether PS NPs could synergistically affect the antibacterial immunity of crabs. We observed that NPs were endocytosed by hemocytes, which are immune cells in crustaceans and are involved in innate immunity. The RNA sequencing data showed that after hemocytes endocytosed NPs, apoptosis and glucose metabolism-related gene expression was significantly induced, resulting in abnormal cell apoptosis and a glucose metabolism disorder. In addition, exposure to NPs resulted in changes in the antimicrobial immunity of crabs, including changes in antimicrobial peptide expression, survival, and bacterial clearance. In summary, NPs could be endocytosed by crab hemocytes, which adversely affected the cell apoptosis, glucose metabolism, and antibacterial immunity of Eriocheir sinensis. This study revealed the effects of NPs on crab immunity and lays the foundation for further exploration of the synergistic effect of NPs and bacteria.

The combined effect of acute hypoxic stress and feeding status on the metabolism of yellow catfish (Pelteobagrus fulvidraco)

Metabolism is one of the most important physiological processes in fish that changes daily depending on the variability of disparate factors. Dissolved oxygen and feeding status are critical to the growth and metabolism of fish. In this study, the effects of dissolved oxygen and feeding status, as well as their interaction on the blood biochemistry and metabolism of yellow catfish (Pelteobagrus fulvidraco) were investigated using a two-factor test. At a dissolved oxygen content of 1.2 mg mL−1, yellow catfish were exposed to hypoxia for 48 h and divided into four experimental groups: normoxia (6.5 mg L−1)-fasting group (C; Control group); normoxia-feeding group (F); hypoxia (1.2 mg L−1)-fasting group (H); and hypoxia-feeding group (FH). Analysis revealed that both hypoxia and feeding caused a short-term increase in the number of red blood cells and hemoglobin concentration in yellow catfish, thereby increasing the oxygen-carrying capacity of the blood. After feeding, the metabolic activity in yellow catfish showed a trend of rising and then falling. Following hypoxia, yellow catfish activated anaerobic glycolysis to provide the energy required by the body, and the mode of metabolism in yellow catfish gradually converted from aerobic to anaerobic. Moreover, the activity of respiratory metabolism enzyme succinate dehydrogenase (SDH) tended to decrease and then increase, while that of lactate dehydrogenase (LDH) tended to increase and then decrease, showing opposing trends. Furthermore, the liver glycogen was mobilized, blood glucose levels increased, and lactic acid accumulation occurred in the short term. Meanwhile, the hypoxia-inducible factor (hif-1α) was activated, the expression of glucose metabolism-related genes (epo, hk1, pfkla, pkma, and gk) dramatically increased, and the activities of the three key enzymes involved in glycolysis (HK, PFK, and PK) were elevated for a short period of time. In conclusion, both hypoxia and feeding altered blood biochemical and metabolic responses in yellow catfish over time, and the metabolic responses were more intense in the post-feeding hypoxia group.

ADAPTOR PROTEIN RUK/CIN85 IS INVOLVED IN THE GLUCOSE METABOLISM REPROGRAMMING IN BREAST CANCER CELLS

Aim. This study aimed to investigate the changes in glucose metabolism in mouse 4T1 breast adenocarcinoma cells with different levels of Ruk/CIN85 expression. Methods. We used 4T1 cells with stable overexpression (subline RukUp) or knockdown (subline RukDown) of Ruk/CIN85, as well as corresponding vector control sublines Mock and Scr. Cells were cultured in the complete RPMI-1640 medium under standard conditions. mRNA expression levels were estimated by RT2-PCR, enzymes activities were measured by spectrophotometric and/or fluorometric assays. Results. Analysis of mRNA expression of glucose metabolism-related genes in RukUp and RukDown cells revealed that glycolysis genes are preferentially overexpressed in RukUp cells, and downregulated in RukDown cells. Thus, RukUp cells were characterized by significantly overexpressed Slc2a1, Gck, Aldoa, and Ldha, while in RukDown cells these genes were either down regulated or not changed. However, the expression of TCA (tricarboxylic acid) cycle enzyme Mdh2 increased dramatically (by 7,8 times) in RukDown cells. In detail, we observed statistically significant changes in the activity of all studied enzymes in RukUp cells (increase by 1,5-1,9 times for glycolysis enzymes and G6PD, and decrease by 1,33-1,69 times for TCA enzymes). However, in RukDown cells we did not find any significant changes in glycolysis enzymes activities, but activities of mitochondrial IDH3 and MDH2 were elevated by 1,65 and 1,59 times, respectively. Conclusions. The results obtained indicate that adaptor protein Ruk/CIN85 is involved in the metabolic reprogramming during breast cancer progression. High level of Ruk/CIN85 expression is associated with potentiation of the Warburg effect.

Serum Levels of the Cytokine TWEAK Are Associated with Metabolic Status in Patients with Prostate Cancer and Modulate Cancer Cell Lipid Metabolism In Vitro

Simple SummaryTWEAK is an inflammatory cytokine related to prostate cancer (PCa) progression that exerts its effects by engaging its cognate receptor Fn14. A soluble form of TWEAK (sTWEAK) has been detected in the PCa microenvironment. Altered levels of circulating sTWEAK are associated with aberrant glucose metabolism. We show that reduced serum levels of sTWEAK are associated with the metabolic status in patients with PCa and that the treatment of PC-3 cells with sTWEAK enhances the expression of genes related to lipid, but not to glucose, metabolism. sTWEAK also increases the lipid uptake and lipid accumulation in PC-3 cells. We corroborated that the observed effects were due to TWEAK/Fn14 engagement by silencing Fn14 expression, which attenuated the aberrant gene and protein expression. Additionally, we observed that the phosphorylation of ERK1/2 and AKT (ser473) were required for TWEAK/Fn14 actions. Thus, the contribution of the sTWEAK/Fn14 axis on PCa metabolism supports its potential as a therapeutic target for PCa.Soluble TWEAK (sTWEAK) has been proposed as a prognostic biomarker of prostate cancer (PCa). We found that reduced serum levels of sTWEAK, together with higher levels of prostate-specific antigen and a higher HOMA-IR index, are independent predictors of PCa. We also showed that sTWEAK stimulus failed to alter the expression of glucose transporter genes (SLC2A4 and SLC2A1), but significantly reduced the expression of glucose metabolism-related genes (PFK, HK1 and PDK4) in PCa cells. The sTWEAK stimulation of PC-3 cells significantly increased the expression of the genes related to lipogenesis (ACACA and FASN), lipolysis (CPT1A and PNPLA2), lipid transport (FABP4 and CD36) and lipid regulation (SREBP-1 and PPARG) and increased the lipid uptake. Silencing the TWEAK receptor (Fn14) in PC-3 cells confirmed the observed lipid metabolic effects, as shown by the downregulation of ACACA, FASN, CPT1A, PNPLA2, FABP4, CD36, SREBP-1 and PPARG expression, which was paralleled by a reduction of FASN, CPT1A and FABP4 protein expression. Specific-signaling inhibitor assays show that ERK1/2 and AKT (ser473) phosphorylation can regulate lipid metabolism-related genes in PCa cells, pointing to the AKT locus as a possible target for PCa. Overall, our data support sTWEAK/Fn14 axis as a potential therapeutic target for PCa.

Dietary carbohydrate sources influence the growth performance, plasma biochemical parameters and expression of genes involved in glucose metabolism in juvenile Pelodiscus sinensis

An 8-week growth trial was conducted to investigate the influences of different dietary carbohydrate sources on growth performance, feed utilization, plasma biochemical parameters and expression of glucose metabolism-related genes in juvenile Chinese soft-shelled turtle, Pelodiscus sinensis. Five isonitrogenous (45 %) and isolipidic (8 %) experimental diets contained 17 % glucose, maltose, sucrose, pregelatinized cassava starch (α-starch) or cellulose, respectively. The results showed that α-starch significantly improved the weight gain rate and specific growth rate of P. sinensis compared to glucose, sucrose and cellulose. No significant difference existed in daily feed intake among all diets. However, turtles fed with cellulose showed a significantly higher feed conversion ratio than that in other treatments except for glucose group. Turtles fed with glucose showed significantly higher plasma glucose content than counterparts in sucrose, α-starch and cellulose treatments. While sucrose induced higher plasma cholesterol and triacylglycerol contents of turtles compared to glucose, maltose, sucrose and α-starch. The plasma insulin in α-starch group showed a higher level than that in glucose group. The glycolysis enzymes including glucokinase and pyruvate kinase in α-starch group exhibited higher mRNA levels than that in other diets, while the mRNA levels of gluconeogenesis enzymes in α-starch group were significantly lower than that in glucose group. The expressions of glycogen synthase and phosphorylase glycogen in glucose group were significantly up-regulated compared with sucrose, α-starch or cellulose groups. In summary, the poor insulin secretion and the up-regulated gluconeogenesis may account for the decreased growth in glucose diets. The most appropriate tested carbohydrate source was α-starch for juvenile P. sinensis based on its positive impacts on growth and metabolism of turtles.

Quercetin\u2011conjugated superparamagnetic iron oxide nanoparticles modulate glucose metabolism-related genes and miR-29 family in the hippocampus of diabetic rats

Quercetin (QC) is a dietary bioflavonoid that can be conjugated with nanoparticles to facilitate its brain bioavailability. We previously showed that quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) reduced the level of blood glucose in diabetic rats. Glucose transporters (GLUTs), insulin-like growth factor-1 (IGF-1), and microRNA-29 (miR-29) play a critical role in brain glucose homeostasis. In the current study, we examined the effects of QCSPION on the expression of glucose metabolism-related genes, and the miR-29 family as a candidate regulator of glucose handling in the hippocampus of diabetic rats. Our in silico analyses introduce the miR-29 family as potential regulators of glucose transporters and IGF-1 genes. The expression level of the miR-29 family, IGF-1, GLUT1, GLUT2, GLUT3, and GLUT4 were measured by qPCR. Our results indicate that diabetes significantly results in upregulation of the miR-29 family and downregulation of the GLUT1, 2, 3, 4, and IGF-1 genes. Interestingly, QCSPIONs reduced miR-29 family expression and subsequently enhanced GLUT1, 2, 3, 4, and IGF-1expression. In conclusion, our findings suggest that QCSPION could regulate the expression of the miR-29 family, which in turn increases the expression of glucose transporters and IGF-1, thereby reducing diabetic complications.

Metformin Attenuates the Metabolic Disturbance and Depression-like Behaviors Induced by Corticosterone and Mediates the Glucose Metabolism Pathway.

Metabolism disturbances are common in patients with depression. The drug metformin has been reported to exhibit antidepressant activity. The purpose of this study was to investigate metabolism disturbances induced by corticosterone (CORT) and determine if metformin can reverse these effects and their accompanying depression-like behaviors. Rats were exposed to corticosterone with or without metformin administration. Depression-like behaviors were tested. Gene expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. In addition, the metabolites were quantified by LC-MS/MS analysis. Metformin attenuated the depression-like behaviors induced by CORT. Furthermore, metformin reversed disturbances in body weight, serum glucose, and triglyceride levels, as well as hepatic TG levels induced by CORT. Metformin normalized the alterations in the expression of glucose metabolism-related genes (PGC-1α, G6pc, Pepck, Gck, PYGL, Gys2, PKLR, GLUT4) and insulin resistance-related genes (AdipoR1, AdipoR2) in the muscles and livers of rats induced by CORT. Metabolomic analysis showed that metformin reversed the effects of CORT on 11 metabolites involved in the pathways of the tricarboxylic acid cycle, glycolysis, and gluconeogenesis (3-phospho-D-glycerate, β-D-fructose 6-phosphate, D-glucose 6-phosphate, and pyruvate). Our findings suggest that metformin can attenuate metabolism disturbances and depression-like behaviors induced by CORT mediating the glucose metabolism pathway.

C-C motif chemokine receptor 9 regulates obesity-induced insulin resistance via inflammation of the small intestine in mice.

Accumulation of adipose tissue macrophages is considered pivotal in the development of obesity-associated inflammation and insulin resistance. In addition, recent studies suggest an involvement of the intestine as the primary organ in inducing hyperglycaemia and insulin resistance. We have reported that the C-C motif chemokine receptor (CCR) CCR9 is associated with intestinal immunity and has a pathogenic role in various liver diseases. However, its contribution to type 2 diabetes is unknown. In the current study, we aimed to clarify the involvement of CCR9 in the pathology of type 2 diabetes and the potential underlying mechanisms. To elucidate how CCR9 affects the development of metabolic phenotypes, we examined the impact of CCR9 deficiency on the pathogenesis of type 2 diabetes using male C57BL/6J (wild-type [WT]) and CCR9-deficient (CCR9 knockout [KO]) mice fed a 60% high-fat diet (HFD) for 12weeks. WT and Ccr9KO mice fed an HFD exhibited a comparable weight gain; however, glucose tolerance and insulin resistance were significantly improved in Ccr9KO mice. Moreover, visceral adipose tissue (VAT) and the liver of Ccr9KO mice presented with less inflammation and increased expression of glucose metabolism-related genes than WT mice. Ccr9 and Ccl25 expression were specifically higher in the small intestine but was not altered by HFD feeding and type 2 diabetes development. Accumulation of IFN-γ-producing CD4+ T lymphocytes and increased intestinal permeability in the small intestine was observed in WT mice following HFD feeding, but these changes were suppressed in HFD-fed Ccr9KO mice. Adoptive transfer of gut-tropic CCR9-expressing T lymphocytes partially reversed the favourable glucose tolerance found in Ccr9KO mice via exacerbated inflammation in the small intestine and VAT. CCR9 plays a central role in the pathogenesis of type 2 diabetes by inducing an inflammatory shift in the small intestine. Our findings support CCR9 as a new therapeutic target for type 2 diabetes via the gut-VAT-liver axis.

Impact of aerobic exercise type on blood flow, muscle energy metabolism, and mitochondrial biogenesis in experimental lower extremity artery disease

Exercise training (ET) is recommended for lower extremity artery disease (LEAD) management. However, there is still little information on the hemodynamic and metabolic adaptations by skeletal muscle with ET. We examined whether hindlimb perfusion/vascularization and muscle energy metabolism are altered differently by three types of aerobic ET. ApoE−/− mice with LEAD were assigned to one of four groups for 4 weeks: sedentary (SED), forced treadmill running (FTR), voluntary wheel running (VWR), or forced swimming (FS). Voluntary exercise capacity was improved and equally as efficient with FTR and VWR, but remained unchanged with FS. Neither ischemic hindlimb perfusion and oxygenation, nor arteriolar density and mRNA expression of arteriogenic-related genes differed between groups. 18FDG PET imaging revealed no difference in the steady-state levels of phosphorylated 18FDG in ischemic and non-ischemic hindlimb muscle between groups, nor was glycogen content or mRNA and protein expression of glucose metabolism-related genes in ischemic muscle modified. mRNA (but not protein) expression of lipid metabolism-related genes was upregulated across all exercise groups, particularly by non-ischemic muscle. Markers of mitochondrial content (mitochondrial DNA content and citrate synthase activity) as well as mRNA expression of mitochondrial biogenesis-related genes in muscle were not increased with ET. Contrary to FTR and VWR, swimming was ineffective in improving voluntary exercise capacity. The underlying hindlimb hemodynamics or muscle energy metabolism are unable to explain the benefits of running exercise.

Changes in expression of genes related to glucose metabolism in liver and skeletal muscle of rats exposed to acute hypoxia

The aim of this study was to determine changes in gene expression associated with glucose metabolism in the liver and soleus muscles of rats exposed to hypoxia to improve work capacity under high altitude conditions. Rats were divided into normobaric normoxia (control) and normobaric hypoxia (hypoxia) groups (n = 7 each), and the hypoxia group was exposed to 10.5% oxygen for 90 min. Glucose metabolism-related gene expression was examined by real-time polymerase chain reaction. In the liver, the expression levels of the glucose utilization-related genes solute carrier family 2 member 1, glucokinase, and liver-type phosphofructokinase and the gluconeogenesis-related gene phosphoenolpyruvate carboxykinase 1 (Pck1) were significantly increased upon hypoxic exposure. In contrast, gene expression in the soleus was unchanged, with the exception of Pck1. The results suggest that under hypoxia, both glucose utilization and gluconeogenesis are accelerated in the liver, and liver glycogen is degraded to maintain blood glucose level.

Starch in aquafeeds: the benefits of a high amylose to amylopectin ratio and resistant starch content in diets for the carnivorous fish, largemouth bass (Micropterus salmoides).

Aquafeeds for carnivorous species face a nutritional-technological conundrum: containing sufficient starch to meet specific manufacturing requirements for binding, extrusion and expansion, but ideally containing as little starch as possible owing to their limited ability to utilise carbohydrates. The present study evaluated the effects of dietary starch with different amylose to amylopectin ratios and resistant starch contents on growth performance, hepatic glycogen accumulation and glucose metabolism of an important cultured carnivorous finfish, largemouth bass (Micropterus salmoides). A common starch source (α-cassava starch (CS)) was tested as is or after being enzymatically de-branched at three different inclusion levels in diets for largemouth bass. Results showed that the increased dietary starch levels compromised performance and high dietary α-CS content led to obvious liver damage. However, the growth performances of fish fed the diets with de-branched starch (DS) were improved, and no manifest liver damages were observed even at the higher inclusion level. The increasing dietary starch contents significantly increased hepatic glycogen accumulation, but not when DS was used. High dietary starch content, without regard to starch sources, had no effect on the expression of glucose metabolism-related genes, except for down-regulation of insulin receptor expression. However, the use of dietary DS promoted the expression of genes involved in the insulin pathway and glycolysis. In conclusion, this study showed that the use of starch sources with a high amylose to amylopectin ratio and resistant starch in the feed for cultured carnivorous finfish could alleviate the hepatic glycogen deposition through regulating the insulin pathway and glycolysis.

LEW.1WR1 Rats have increased insulin levels and liver lipid lipolytic gene expression during their type 1 diabetes susceptibility window.

LEW.1WR1(1WR1) rats have increased type 1 diabetes (T1D) onset with the administration of polyinosinic‐polycytidylic acid (PIC). The susceptibility window of inducible T1D in the 1WR1 rat occurs between 21–35 days of life. The susceptibility of this model is related to FAT10 overexpression, a ubiquitin‐like protein that plays an unclear role in disease induction and the regulation of lipid metabolism. We hypothesized that these rodents have altered liver lipid metabolism due to increased FAT 10 gene expression in their livers and increased circulating insulin levels which can lead to decreased liver insulin sensitivity and increased beta‐cell sensitivity to inflammation. The objective of this study was to compare the insulitis status and liver gene expression in both control and treated 1WR1 rats during disease induction with a T1D‐resistant strain of rat, the LEW/SSNHsd.Using immunohistochemistry we observed higher T cell infiltration in the 1WR1 treated rats compared to the control strain, the LEW/SsNHsd(SsNHsd) PIC‐treated rat. By correlating plasma glucose levels measured by glucometer with this finding we confirmed that the 1WR1 rats were not undergoing significant insulitis at the time point we selected. We also observed that the rats have significantly fewer total islets than the SsNHsd rats but remained normoglycemic. Interestingly the 1WR1 treated rat had significantly increased insulin levels compared to the SsNHsd rats, as previous studies showed a 3 fold increase in the 1WR1 rat compared to Wistar Furth rats in a similar study(unpublished data). Both groups of the 1WR1 rats also had increased liver FAT10 gene expression compared to the SsNHsd. We measured liver lipid lipolytic gene expression to assess the metabolic status of the livers at this time point. We observed 1WR1 rats have increased expression of genes related to lipid catabolism like SREBP‐1 (Sterol Regulatory Element‐binding Protein‐1), ATGL (Adipose triglyceride lipase), DGAT1(diacylglycerol acyltransferase‐1), DGAT2(diacylglycerol acyltransferase‐2) and lower expression of glucose metabolism‐related genes like GLUT2(Glucose transporter 2), suggesting that the 1WR1 rats may have had a liver sensitivity response to the hyperinsulinemia. In conclusion, 1WR1 rats have reduced insulin sensitivity in the context of increased inflammation due to PIC injection which led to beta‐cell sensitivity and eventual T‐cell mediated destruction.Support or Funding InformationDepartment of Chemistry, UAHDepartment of Biology, UAHCollege of Science, UAHOffice of Provost, UAH

Chicoric acid mitigates impaired insulin sensitivity by improving mitochondrial function.

Mitochondrial dysfunction is associated with insulin resistance. Although chicoric acid (CA) is known to have beneficial effects on insulin sensitivity, the involvement of mitochondrial function has not been elucidated yet. Here, we investigated the effect of CA on insulin resistance and mitochondrial dysfunction. In palmitate-induced insulin-resistant C2C12 myotubes, CA improved impaired glucose uptake and insulin signaling pathways, along with enhanced mitochondrial membrane potential and oxygen consumption. CA treatment in diet-induced obese mice ameliorated glucose tolerance and increased insulin sensitivity. CA treatment also recovered the dysregulated expression of glucose metabolism-related genes in the high-fat-fed mice. CA significantly increased the mitochondrial DNA content, citrate synthase, and ATP content, as well as the expression of genes related to mitochondrial biogenesis and oxidative phosphorylation in the liver and skeletal muscle in high-fat- fed obese mice. These findings suggested that CA attenuates insulin resistance and promotes insulin sensitivity by enhancing mitochondrial function.

The variation of serum glucose, hepatic glycogen content and expression of glucose metabolism-related genes in hybrid grouper (female Epinephelus fuscoguttatus × male Epinephelus lanceolatus) in response to intraperitoneal insulin infusion

The present study was conducted to investigate the effects of insulin on serum glucose, hepatic glycogen content and expression of glucose metabolism-related genes in hybrid grouper. Triplicate groups of five fish were sampled at the 0, 1, 3, 6, 12, 24 or 48-h time point post-bovine insulin (5 μg 100/g fish body mass) injection. A significant decrease of serum glucose content was observed along with the depletion of hepatic glycogen content at the 12-h time point following insulin injection. Hepatic gene expression analysis revealed that the infusion of insulin significantly increased the expression of glucose transporters (GLUTs), GLUT1b and GLUT2. The transcription of gluconeogenesis-related genes, fructose-1,6-bisphosphatase 1a and glucose-6-phosphatase a catalytic subunit tandem duplicate 2, was significantly decreased at the 12-h time point, while the expression of glycolysis-related genes, phosphofructokinase liver b and pyruvate kinase L/R, was significantly up-regulated at the 24-h time point post-insulin injection. Meanwhile, the expression of glucokinase significantly increased immediately following insulin administration. The expression of glycogen synthase liver type significantly decreased at the 12-h time point, while the expression of glycogen phosphorylase liver type was significantly elevated at the 24-h time point following insulin injection. These results suggested that insulin could affect glucose metabolism through regulating gluconeogenesis, glycolysis and glycogen metabolism at the transcriptional level.

Effects of Apelin-13 on expression levels of glucose and lipid metabolism-related genes in the liver and skeletal muscle of diabetic rats

Objective To investigate the effects of exogenous Apelin-13 on the expression of glucose and fatty acid metabolism-related genes in the liver and skeletal muscle of diabetic rats. Methods Forty male Wister rats were randomly divided into a control group (n=8) and an experimental group (n=32). In the experimental group, a rat model of type 2 diabetes mellitus was established by a high-glucose and high-fat diet and intraperitoneal injection of streptozotocin (STZ). The diabetic rats were randomized into a diabetic model group and an Apelin-13 treatment group with 14 rats in each group.Rats in the Apelin-13 treatment group were intraperitoneally injected with 0.1 μmol·kg·d-1 Apelin-13 for 10 weeks, while the control group and the diabetic model group were injected with an equal volume of 0.9% NaCl solution for 10 weeks.At the end of the 10 week treatment, fasting blood glucose values in each group were measured.Levels of mRNA expression of glucose-6-phosphate (G-6-P), phosphoenolpyruvate carboxykinase (PEPCK), peroxisome proliferator-activated receptor alpha (PPAR-α), acy1-CoA synthetase long-chain family member1 (ACSL1), and carnitine palmitoyltransferase1 (CPT1) in the liver and levels of mRNA expression of PPAR-α and glucose transporter type 4 (GLUT4) in skeletal muscle were detected by real-time fluorescence quantitative polymerase chain reaction (PCR). Results Levels of mRNA expression of liver PPAR-α, liver ACSL1, liver CPT1, and GLUT4 in skeletal muscle were lower in the diabetic model group (0.309±0.073, 0.508±0.056, 0.389±0.118 and 0.289±0.066, respectively) than in the control group (0.971±0.028, 0.990±0.015, 0.987±0.015 and 0.994±0.009, respectively) (all P 0.05). Conclusions Apelin-13 increases the expression of the PPAR, ACSL1, and CPT1 genes in the liver and, to a certain extent, improves fatty acid oxidation metabolism in the liver in type 2 diabetic rats.It also increases the expression of the G-6-P and PEPCK genes, promotes gluconeogenesis in the liver, and may be related to the development of type 2 diabetes.In skeletal muscle, Apelin-13 increases GLUT4 gene expression, moderately improves skeletal muscle metabolism and may play a role in the regulation of oxidative stress. Key words: Diabetes mellitus; Carbohydrate metabolism; Lipid metabolism; Apelin-13