Modulation Of Glucose Metabolism Research Articles

Ganoderma lucidum Modulates Glucose, Lipid Peroxidation and Hepatic Metabolism in Streptozotocin-Induced Diabetic Pregnant Rats.

The consumption of functional foods, such as mushrooms, apparently influences Gestational Diabetes Mellitus (GDM), and brings benefits to maternal-fetal health. Ganoderma lucidum contains a variety of bioactive compounds, such as polysaccharides, proteins and polyphenols that are able to control blood glucose and be used in anti-cancer therapy. We aimed to evaluate the effects of the consumption of Ganoderma lucidum (Gl) on maternal-fetal outcomes in streptozotocin-induced GDM (GDM-STZ). Pregnant rats were exposed to Gl (100 mg/kg/day) before and after the induction of GDM-STZ (single dose 40 mg/kg) on the eighth pregnancy day. Biochemical and oxidative stress parameters, reproductive performance and morphometry of fetuses were assessed. Gl reduced the glycemic response in the oral glucose tolerance test. Moreover, Gl decreased AST and ALT activities. GDM increased lipid peroxidation, which was reverted by Gl. Catalase and glutathione peroxidase activities were decreased in GDM and the administered Gl after the fetus implantation increased catalase activity. Measurements of the fetal head, thorax, craniocaudal and tail showed greater values in fetuses from rats exposed to Gl compared to GDM. Ganoderma lucidum has an encouraging nutritional and medicinal potential against GDM, since it modifies glucose metabolism, reduces lipid peroxidation, and has protective effects in fetuses born from GDM dams.

Cortisol modulates glucose metabolism and oxidative response after acute high temperature stress in Pacific oyster Crassostrea gigas

Cortisol is the main stress hormone that plays crucial roles in energy metabolism and immune response in vertebrates. In the present study, the homologues of 11β-hydroxysteroid dehydrogenase type 1 (designated Cg11β-HSD1) and 5α-reductase 1 (designated Cg5αR1), the key enzymes related to cortisol metabolism, were identified from Pacific oyster Crassostrea gigas. The Cg11β-HSD1 harbored a conserved SDR domain, and Cg5αR1 contained a Steroid_dh domain and three transmembrane domains. The mRNA transcripts of Cg11β-HSD1 and Cg5αR1 were constitutively expressed in all the examined tissues of oysters, with the highest expression level in haemocytes and labial palp, respectively. After acute high temperature stress (28 °C), the mRNA expression level of Cg11β-HSD1 in hepatopancreas significantly up-regulated at 6 h and 12 h, and that of Cg5αR1 significantly up-regulated at 6 h, compared with the Blank group (11 °C). The concentration of cortisol and glucose, as well as the activities of superoxide dismutase (SOD) and catalase (CAT) in hepatopancreas all significantly up-regulated after acute high temperature stress, while the glycogen concentration in adductor muscle decreased significantly at 6 h and 12 h. After the blockage of Cg11β-HSD1 with metyrapone, the cortisol concentration and the activities of SOD and CAT significantly decreased after acute high temperature stress, the glucose concentration in hepatopancreas significantly increased at 24 h, and the glycogen concentration in adductor muscle significantly increased at 6 h. These results collectively suggested that cortisol played a crucial role in regulating glucose metabolism and oxidative response in oysters upon acute high temperature stress.

Biochemical Functions and Clinical Characterizations of the Sirtuins in Diabetes-Induced Retinal Pathologies.

Diabetic retinopathy (DR) is undoubtedly one of the most prominent causes of blindness worldwide. This pathology is the most frequent microvascular complication arising from diabetes, and its incidence is increasing at a constant pace. To date, the insurgence of DR is thought to be the consequence of the intricate complex of relations connecting inflammation, the generation of free oxygen species, and the consequent oxidative stress determined by protracted hyperglycemia. The sirtuin (SIRT) family comprises 7 histone and non-histone protein deacetylases and mono (ADP-ribosyl) transferases regulating different processes, including metabolism, senescence, DNA maintenance, and cell cycle regulation. These enzymes are involved in the development of various diseases such as neurodegeneration, cardiovascular pathologies, metabolic disorders, and cancer. SIRT1, 3, 5, and 6 are key enzymes in DR since they modulate glucose metabolism, insulin sensitivity, and inflammation. Currently, indirect and direct activators of SIRTs (such as antagomir, glycyrrhizin, and resveratrol) are being developed to modulate the inflammation response arising during DR. In this review, we aim to illustrate the most important inflammatory and metabolic pathways connecting SIRT activity to DR, and to describe the most relevant SIRT activators that might be proposed as new therapeutics to treat DR.

Pasta Structure Affects Mastication, Bolus Properties, and Postprandial Glucose and Insulin Metabolism in Healthy Adults

ABSTRACTBackgroundStructure and protein–starch interactions in pasta products can be responsible for lower postprandial glycemic responses compared with other cereal foods.ObjectivesWe tested the effect on postprandial glucose metabolism induced by 2 pasta products, couscous, and bread, through their structural changes during mastication and simulated gastric digestion.MethodsTwo randomized controlled trials (n = 30/trial) in healthy, normal-weight adults (mean BMI of 23.9 kg/m2 (study 1) and 23.0 kg/m2 (study 2)) evaluated postprandial glucose metabolism modulation to portions of durum wheat semolina spaghetti, penne, couscous, and bread each containing 50 g available carbohydrate. A mastication trial involving 26 normal-weight adults was conducted to investigate mastication processes and changes in particle size distribution and microstructure (light microscopy) of boluses after mastication and in vitro gastric digestion.ResultsBoth pasta products resulted in lower areas under the 2-h curve for blood glucose (−40% for spaghetti and −22% for penne compared with couscous; −41% for spaghetti and −30% for penne compared with bread), compared with the other grain products (P < 0.05). Pasta products required more chews (spaghetti: 34 ± 18; penne: 38 ± 20; bread: 27 ± 13; couscous: 24 ± 17) and longer oral processing (spaghetti: 21 ± 13 s; penne: 23 ± 14 s; bread: 18 ± 9 s; couscous: 14 ± 10 s) compared with bread or couscous (P < 0.01). Pastas contained more large particles (46–67% of total particle area) compared with bread (0–30%) and couscous (1%) after mastication and in vitro gastric digestion. After in vitro gastric digestion, pasta samples still contained large areas of nonhydrolyzed starch embedded within the protein network; the protein in bread and couscous was almost entirely digested, and the starch was hydrolyzed.ConclusionsPreservation of the pasta structure during mastication and gastric digestion explains slower starch hydrolysis and, consequently, lower postprandial glycemia compared with bread or couscous prepared from the same durum wheat semolina flour in healthy adults.The postprandial in vivo trials were registered at clinicaltrials.gov as NCT03098017 and NCT03104686.

Impact of anti-diabetic sodium-glucose cotransporter 2 inhibitors on tumor growth of intractable hematological malignancy in humans

Under the dysfunction of mitochondria, cancer cells preferentially utilize both glycolytic and pentose phosphate pathways rather than electron transport chains to desperately generate adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH), classically recognized as the Warburg effect. Based on this background, the present study tested the hypothesis that anti-diabetic sodium-glucose cotransporter 2 (SGLT2) inhibitors would exert a tumor-suppressive impact on intractable human hematological malignancies via the modulation of glucose metabolism within cells and cell cycles. The level of mRNA for SGLT2 was remarkably elevated in leukemic cells from patients with adult T-cell leukemia (ATL), one of the most intractable blood cancers in humans, and as well as in two kinds of ATL cell lines (MT-1 and MT-2). Two kinds of SGLT2 inhibitors, Luseogliflozin and Tofogliflozin substantially suppressed the proliferation of MT-1 and MT-2 cells in both adherent and anchorage-independent culture conditions. Such a suppressive effect on tumor cell growth was reproduced by Luseogliflozin in leukemic cells in peripheral blood from patients with ATL. In MT-2 cells, both of SGLT2 inhibitors considerably attenuated glucose uptake, intracellular ATP levels, and NADPH production, resultantly enhancing cell cycle arrest at the G0/G1 phase. From the standpoint of metabolic oncology, the present study suggests that SGLT2 inhibitors would be a promising adjunctive option for the treatment of the most intractable human hematological malignancies like ATL.

An NF-\u03baB/OVOL2 circuit regulates glucose import and cell survival in non-small cell lung cancer

BackgroundTumor cells tend to utilize glycolysis rather than aerobic respiration even under aerobic conditions. OVOL2, an inhibitory C2H2 zinc finger transcription factor, is a potential tumor suppressor in cancers. However, the association between OVOL2 and tumor energy metabolism is unknown.MethodsWestern blotting was used to determine the expression of OVOL2 in different non-small cell lung cancer (NSCLC) cell lines and mouse models. The metabolic parameters in NSCLC cells following overexpression or knockdown OVOL2 were examined. To define the mechanism by which OVOL2 regulates aerobic glycolysis, interacting protein of OVOl2 and downstream molecular events were identified by luciferase assay and co-immunoprecipitation. We documented the regulatory mechanism in mouse xenograft models. Finally, clinical relevance of OVOL2, NF-κB signaling and GLUT1 was measured by immunostaining.ResultsOVOL2 is downregulated in NSCLC and overexpression of OVOL2 inhibits the survival of cancer cells. Moreover, OVOL2 directly binds to P65 and inhibits the recruitment of P300 but facilitates the binding of HDAC1 to P65, which in turn negatively regulates NF-κB signaling to suppress GLUT1 translocation and glucose import. In contrast, OVOL2 expression is negatively regulated by NF-κB signaling in NSCLC cells via the ubiquitin–proteasome pathway. Re-expression of OVOL2 significantly compromise NF-κB signaling-induced GLUT1 translocation, aerobic glycolysis in NSCLC cells and mouse models. Immunostaining revealed inverse correlations between the OVOL2 and phosphorylated P65 levels and between the OVOL2 and membrane GLUT1 levels, and a strong correlation between the phosphorylated P65 and membrane GLUT1 levels.ConclusionsThese results suggest a regulatory circuit linking NF-κB and OVOL2, which highlights the role of NF-κB signaling and OVOL2 in the modulation of glucose metabolism in NSCLC.5S647uSA4FfDHArbVFhiZ4Video

LncRNA Linc00173 modulates glucose metabolism and multidrug chemoresistance in SCLC: Potential molecular panel for targeted therapy

lncRNA Linc00173 modulates glucose metabolism and multidrug chemoresistance in SCLC: Potential molecular panel for targeted therapy

The Impact of Accelerated HF-rTMS on Canine Brain Metabolism: An [18F]-FDG PET Study in Healthy Beagles.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been proven to be a useful tool for the treatment of several severe neuropsychiatric disorders. Accelerated (a)rTMS protocols may have the potential to result in faster clinical improvements, but the effects of such accelerated paradigms on brain function remain to be elucidated.ObjectivesThis sham-controlled arTMS study aimed to evaluate the immediate and delayed effects of accelerated high frequency rTMS (aHF-rTMS) on glucose metabolism in healthy beagle dogs when applied over the left frontal cortex.MethodsTwenty-four dogs were randomly divided into four unequal groups: five active (n = 8)/ sham (n = 4) stimulation sessions (five sessions in 1 day), 20 active (n = 8)/ sham (n = 4) stimulation sessions (five sessions/ day for 4 days), respectively. [18F] FDG PET scans were obtained at baseline, 24 h poststimulation, after 1 and 3 months post the last stimulation session. We explicitly focused on four predefined regions of interest (left/right prefrontal cortex and left/right hippocampus).ResultsOne day of active aHF-rTMS- and not sham- significantly increased glucose metabolism 24 h post-active stimulation in the left frontal cortex only. Four days of active aHF-rTMS only resulted in a nearly significant metabolic decrease in the left hippocampus after 1 month.ConclusionsLike in human psychiatric disorders, active aHF-rTMS in healthy beagles modifies glucose metabolism, although differently immediately or after 1 month post stimulation. aHF-rTMS may be also a valid option to treat mentally disordered dogs.

Autonomous sensing of the insulin peptide by an olfactory G protein-coupled receptor modulates glucose metabolism

Along with functionally intact insulin, diabetes-associated insulin peptides are secreted by β cells. By screening the expression and functional characterization of olfactory receptors (ORs) in pancreatic islets, we identified Olfr109 as the receptor that detects insulin peptides. The engagement of one insulin peptide, insB:9-23, with Olfr109 diminished insulin secretion through Gi-cAMP signaling and promoted islet-resident macrophage proliferation through a β cell-macrophage circuit and a β-arrestin-1-mediated CCL2 pathway, as evidenced by β-arrestin-1-/- mouse models. Systemic Olfr109 deficiency or deficiency induced by Pdx1-Cre+/-Olfr109fl/fl specifically alleviated intra-islet inflammatory responses and improved glucose homeostasis in Akita- and high-fat diet (HFD)-fed mice. We further determined the binding mode between insB:9-23 and Olfr109. A pepducin-based Olfr109 antagonist improved glucose homeostasis in diabetic and obese mouse models. Collectively, we found that pancreatic β cells use Olfr109 to autonomously detect self-secreted insulin peptides, and this detection arrests insulin secretion and crosstalks with macrophages to increase intra-islet inflammation.

Gut microbiota-derived metabolites are novel targets for improving insulin resistance

The gut microbiota plays a key role in metabolic diseases. Gut-microbiota-derived metabolites are found in different dietary sources, including: Carbohydrate (acetate, propionate, butyrate, also known as short-chain fatty acids, as well as succinate); protein (hydrogen sulfide, indole, and phenylacetic acid); and lipids (resveratrol-, ferulic acid-, linoleic acid-, catechin- and berry-derived metabolites). Insulin resistance, which is a global pandemic metabolic disease that progresses to type 2 diabetes mellitus, can be directly targeted by these metabolites. Gut-microbiota-derived metabolites have broad effects locally and in distinct organs, in particular skeletal muscle, adipose tissue, and liver. These metabolites can modulate glucose metabolism, including the increase in glucose uptake and lipid oxidation in skeletal muscle, and decrease in lipogenesis and gluconeogenesis associated with lipid oxidation in the liver through activation of phosphatidylinositol 3-kinase - serine/threonine-protein kinase B and AMP-activated protein kinase. In adipose tissue, gut-microbiota-derived metabolites stimulate adipogenesis and thermogenesis, inhibit lipolysis, and attenuate inflammation. Importantly, an increase in energy expenditure and fat oxidation occurs in the whole body. Therefore, the therapeutic potential of current pharmacological and non-pharmacological approaches used to treat diabetes mellitus can be tested to target specific metabolites derived from intestinal bacteria, which may ultimately ameliorate the hyperglycemic burden.

Phytochemicals from the Cocoa Shell Modulate Mitochondrial Function, Lipid and Glucose Metabolism in Hepatocytes via Activation of FGF21/ERK, AKT, and mTOR Pathways.

The cocoa shell is a by-product that may be revalorized as a source of bioactive compounds to prevent chronic cardiometabolic diseases. This study aimed to investigate the phytochemicals from the cocoa shell as targeted compounds for activating fibroblast growth factor 21 (FGF21) signaling and regulating non-alcoholic fatty liver disease (NAFLD)-related biomarkers linked to oxidative stress, mitochondrial function, and metabolism in hepatocytes. HepG2 cells treated with palmitic acid (PA, 500 µmol L−1) were used in an NAFLD cell model. Phytochemicals from the cocoa shell (50 µmol L−1) and an aqueous extract (CAE, 100 µg mL−1) enhanced ERK1/2 phosphorylation (1.7- to 3.3-fold) and FGF21 release (1.4- to 3.4-fold) via PPARα activation. Oxidative stress markers were reduced though Nrf-2 regulation. Mitochondrial function (mitochondrial respiration and ATP production) was protected by the PGC-1α pathway modulation. Cocoa shell phytochemicals reduced lipid accumulation (53–115%) and fatty acid synthase activity (59–93%) and prompted CPT-1 activity. Glucose uptake and glucokinase activity were enhanced, whereas glucose production and phosphoenolpyruvate carboxykinase activity were diminished. The increase in the phosphorylation of the insulin receptor, AKT, AMPKα, mTOR, and ERK1/2 conduced to the regulation of hepatic mitochondrial function and energy metabolism. For the first time, the cocoa shell phytochemicals are proved to modulate FGF21 signaling. Results demonstrate the in vitro preventive effect of the phytochemicals from the cocoa shell on NAFLD.

Trans‐ferulic acid attenuates hyperglycemia‐induced oxidative stress and modulates glucose metabolism by activating AMPK signaling pathway in vitro

Adenosine monophosphate-activated protein kinase (AMPK) is a potent metabolic regulator and an attractive target for antidiabetic activators. Here we report for the first that, trans-ferulic acid (TFA) is a potent dietary bioactive molecule of hydroxycinnamic acid derivative for the activation of AMPK with a maximum increase in phosphorylation (2.71/2.67±0.10; p<.001 vs. high glucose [HG] control) in hyperglycemia-induced human liver cells (HepG2) and rat skeletal muscle cells (L6), where HG suppresses the AMPK pathway. It was also observed that TFA increased activation of AMPK in a dose- and time-dependent manner and also increased the phosphorylation of acetyl-CoA carboxylase (ACC), suggesting that it may promotes fatty acid oxidation; however, pretreatment with compound C reversed the effect. In addition, TFA reduced the level of intracellular reactive oxygen species (ROS) and nitric oxide (NO) induced by hyperglycemia and subsequently increased the level of glutathione. Interestingly, TFA also upregulated the glucose transporters, GLUT2 and GLUT4, and inhibited c-Jun N-terminal protein kinase (JNK1/2) by decreasing the phosphorylation level in tested cells under HG condition. Our studies provide critical insights into the mechanism of action of TFA as a potential natural activator of AMPK under hyperglycemia. PRACTICAL APPLICATIONS: Hydroxycinnamic acid derivatives possess various pharmacological properties and are found to be one of the most ubiquitous groups of plant metabolites in almost all dietary sources. However, the tissue-specific role and its mechanism under hyperglycemic condition remain largely unknown. The present study showed that TFA is a potent activator of AMPK under HG condition and it could be used as a therapeutic agent against hyperglycemia in type 2 diabetes.

Triterpenoids impede the fibrillation and cytotoxicity of human islet amyloid polypeptide

The inhibition of human islet amyloid polypeptide (hIAPP) deposition to block its toxicity is an important strategy for the prevention and treatment of type II diabetes mellitus (T2DM).Natural compounds with pharmacological properties and low toxicity can serve as a good point to discover potential inhibitors of protein misfolding, which may be useful for the treatment of various amyloidosis-related diseases. Previous studies have reported that triterpenoids, such as maslinic acid (MA) and momordicin I (MI), can modulate glucose metabolism partially by reducing insulin resistance. However, the internal antidiabetic mechanism of these triterpenoids remains unclear. In this study, we examined the inhibition and disaggregation of MAandits isomer MI on the fibrillation of hIAPP using various experimental and computational approaches. The assembly behaviors and peptide-induced cytotoxicity of hIAPP could be effectively resisted by MA and MI. Moreover, the interaction of the two triterpenoids with hIAPP displayed a spontaneous and exothermic process. Moreover, molecular dynamics simulation results of different peptides revealed that MA and MI could bind to Asn and other non-polar residues near the core C-terminal region and reduce the oligomerization of hIAPP. The binding affinity was predominantly contributed by hydrophobic, electrostatic and hydrogen bonding interactions. The present work provides valuable data for MA and MI to treat T2DM and amyloidosis-related diseases.

Extracellular Vesicles Induce an Aggressive Phenotype in Luminal Breast Cancer Cells Via PKM2 Phosphorylation.

BackgroundAerobic glycolysis is a hallmark of glucose metabolism in cancer. Previous studies have suggested that cancer cell–derived extracellular vesicles (EVs) can modulate glucose metabolism in adjacent cells and promote disease progression. We hypothesized that EVs originating from cancer cells can modulate glucose metabolism in recipient cancer cells to induce cell proliferation and an aggressive cancer phenotype.MethodsTwo breast cancer cell lines with different levels of glycolytic activity, MDA-MB-231 cells of the claudin-low subtype and MCF7 cells of the luminal type, were selected and cocultured as the originating and recipient cells, respectively, using an indirect coculture system, such as a Transwell system or a microfluidic system. The [18F]fluorodeoxyglucose (FDG) uptake by the recipient MCF7 cells was assessed before and after coculture with MDA-MB-231 cells. Proteomic and transcriptomic analyses were performed to investigate the changes in gene expression patterns in the recipient MCF7 cells and MDA-MB-231 cell-derived EVs.ResultsFDG uptake by the recipient MCF7 cells significantly increased after coculture with MDA-MB-231 cells. In addition, phosphorylation of PKM2 at tyrosine-105 and serine-37, which is necessary for tumorigenesis and aerobic glycolysis, was highly activated in cocultured MCF7 cells. Proteomic profiling revealed the proliferation and dedifferentiation of MCF7 cells following coculture with MDA-MB-231 cells. Transcriptomic analysis demonstrated an increase in glycolysis in cocultured MCF7 cells, and the component analysis of glycolysis-related genes revealed that the second most abundant component after the cytoplasm was extracellular exosomes. In addition, proteomic analysis of EVs showed that the key proteins capable of phosphorylating PKM2 were present as cargo inside MDA-MB-231 cell-derived EVs.ConclusionsThe phenomena observed in this study suggest that cancer cells can induce a phenotype transition of other subtypes to an aggressive phenotype to consequently activate glucose metabolism via EVs. Therefore, this study could serve as a cornerstone for further research on interactions between cancer cells.

(-)-Epicatechin and β-glucan from highland barley grain modulated glucose metabolism and showed synergistic effect via Akt pathway

In this study, (-)epicatechin (EC) and β-glucan (BG) were identified as the active compounds in highland barley grain that modulated glucose metabolism. The mechanism underlying EC may target on insulin receptor and regulate target on insulin receptor substrate-1 /phosphatidylinositol 3-kinase / protein kinase B (Akt) pathway, and BG may target on mammalian rapamycin receptor and regulate the Akt pathway. EC and BG showed anti-hyperglycemic effects and modulated hepatic glucose metabolism in mice with impaired glucose tolerance. Moreover, EC combined with BG showed synergistic effects on the Akt pathway, thereby improved glucose uptake through up-regulating glucose transporter 4, improved glycogen synthesis by down-regulating glycogen synthase kinase-3β, and inhibiting gluconeogenesis by down-regulating phosphoenolpyruvate carboxykinase 1 protein expression. These results provide evidence of a whole highland barley grain diet to prevent type 2 diabetes or developing EC and BG as new dietary supplement.

Abstract 10928: Chlorogenic Acid Ameliorates Pressure Overload-Induced Cardiac Hypertrophy in Mouse Models

Introduction: Cardiac hypertrophy leading to heart failure is one of the critical causes of morbidity and mortality. Although social interest in treatment and prevention of cardiovascular disease is high, sufficient outcome has not been obtained yet. Chlorogenic acid (CGA) is one of the most abundant phenolics in plants, and is called caffeic acid. Recently, the cardioprotective effects of CGA which ameliorate isoproterenol-induced hypertrophy in vitro research have been reported. However, it has not been elucidated whether CGA affects cardiac hypertrophy in vivo models with TAC. Hypothesis: We assessed the hypothesis that the administration of CGA has protective effect on TAC-induced cardiac hypertrophy. Methods: We used mouse models of cardiac hypertrophy induced by TAC for four weeks. Mice were randomly assigned to sham, TAC, and TAC+CGA groups. CGA was administered at dose of 40mg/kg intraperitoneally once a day for four weeks after the TAC operation. cardioprotective effect was investigated by echocardiography and histological analysises. In addition, immunoblot and metabolome analysises and biomedical assays were conducted in excised hearts. Statistical analysis was performed by one-way ANOVA. All data are expressed as mean ± SD. Statistical significance was defined as P &lt; 0.05. Results: We evaluated sham group (n=8), TAC group (n=7), TAC+CGA group (n=7) four weeks after TAC operation. TAC group showed an increase of heart weight, which was attenuated by CGA (120.3±9.3mg, 148.8±9.0mg, 126.6±6.2mg, p&lt;0.05). Consistently, echocardiography revealed that the change of myocardial diastolic wall thickness (0.79±0.1mm, 1.13±0.1mm, 0.93±0.1mm, p&lt;0.05). Histological analysis indicated that fibrosis induced by TAC was alleviated by CGA. According to immunoblot analysis, TAC group showed overexpression of TGF-β, IL-6, and TNF-α. In addition, the enhancements of glycolysis and TCA cycle were indicated in metabolome analysis. These changes were modulated by CGA administration. Conclusion: In conclusion, the present study revealed that CGA administration ameliorates pressure overload-induced cardiac hypertrophy in rodent model. As a key factor, expression of inflammatory cytokines and modulation of glucose metabolism were observed.

Gestational Diabetes Mellitus-Associated Hyperglycemia Impairs Glucose Transporter 3 Trafficking in Trophoblasts Through the Downregulation of AMP-Activated Protein Kinase.

AMP-activated protein kinase (AMPK) is an important regulator of glucose metabolism, and glucose transporter 3 (GLUT3) is an efficient glucose transporter in trophoblasts. Whether placental AMPK and GLUT3 respond accordingly to gestational diabetes mellitus (GDM) remains uncertain. Here, we explored the regulatory role of AMPK in the GLUT3-dependent uptake of glucose by placental trophoblasts and the viability of the cells. In this study, the level of glycolysis in normal and GDM-complicated placentas was assessed by LC-MS/MS. The trophoblast hyperglycemia model was induced by the incubation of HTR8/SVneo cells with a high glucose concentration. GDM animal models were generated with db/ + mice and C57BL/6J mice fed a high-fat diet, and AMPK was manipulated by the oral administration of metformin. The uptake of glucose by trophoblasts was assessed using 2-NBDG or 2-deoxy-D-[3H] glucose. The results showed that GDM is associated with impaired glycolysis, AMPK activity, GLUT3 expression in the plasma membrane (PM) and cell survival in the placenta. Hyperglycemia induced similar changes in trophoblasts, and these changes were rescued by AMPK activation. Both hyperglycemic db/ + and high-fat diet-induced GDM mice exhibited a compromised AMPK–GLUT3 axis and suppressed cell viability in the placenta as well as excessive fetal growth, and all of these effects were partially alleviated by metformin. Taken together, our findings support the notion that AMPK activation upregulates trophoblast glucose uptake by stimulating GLUT3 translocation, which is beneficial for viability. Thus, the modulation of glucose metabolism in trophoblasts by targeting AMPK might ameliorate the adverse intrauterine environment caused by GDM.

WITHDRAWN: lncRNA Linc00173 modulates glucose metabolism and multidrug chemoresistance in SCLC: Potential molecular panel for targeted therapy

This article has been withdrawn at the request of the editor-in-chief. Following publication of this article, the editor-in-chief discovered evidence of image duplication in Figures 1I, 1J, 3F, S5B, and S6B. Given the duplication of several western blots representing several gene products, the editor-in-chief has lost faith in the findings presented in this article. The authors maintain that these image duplications were the result of errors in file management and do not affect the conclusions of the study. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Metabolites of gut microbiome are associated with glucose metabolism in non-diabetic obese adults: a Chinese monozygotic twin study

BackgroundEvidence suggests gut microbiome is associated with diabetes. However, it’s unclear whether the association remains in non-diabetic participants. A Chinese monozygotic twin study, in which the participants are without diabetes, and are not taking any medications, was conducted to explore the potential association.MethodsNine pairs of adult monozygotic twins were enrolled and divided into two twin-pair groups (a and b). Clinical and laboratory measurements were conducted. Visceral adipose tissue (VAT) was assessed. Fecal samples were collected to analyze the microbiome composition by 16S rDNA gene amplicon sequencing. Liquid chromatography mass spectrometry was performed to detect the metabolites.ResultsThe participants aged 53 years old averagely, with 8 (88.9%) pairs were women. All the participants were obese with VAT higher than 100 cm2 (152.2 ± 31.6). There was no significant difference of VAT between the twin groups (153.6 ± 30.4 cm2 vs. 150.8 ± 29.5 cm2, p = 0.54). Other clinical measurements, including BMI, lipid profiles, fasting insulin and blood glucose, were also not significantly different between groups (p ≥ 0.056), whereas HbA1c level of group a is significantly higher than group b (5.8 ± 0.3% vs. 5.6 ± 0.2%, p = 0.008). The number and richness of OTUs are relatively higher in group a, and 13 metabolites were significantly different between two groups. Furthermore, several of the 13 metabolites could be significantly linked to special taxons. The potential pathway involved drug metabolism-other enzymes, Tryptophan metabolism and Citrate cycle.ConclusionsGut microbiome composition and their metabolites may modulate glucose metabolism in obese adults without diabetes, through Tryptophan metabolism, Citrate cycle and other pathways.

Biological roles of l-carnitine in oocyte and early embryo development.

Poor oocyte quality is responsible for female infertility. Multiple studies have been carried out to find supplements to enhance oocyte quality and mitigate infertility problems. l-carnitine and its derivatives have diverse roles in developing oocytes and early embryos. This review focuses on the in vitro and in vivo studies that using l-carnitine alone or in combination with other supplements for oocyte quality enhancement. The key roles of l-carnitine in oocyte quality and embryo growth were summarized, and the underlying mechanism was also elucidated. l-carnitine helps in the lipid metabolism process by controlling the transfer of fatty acids to mitochondria for β-oxidation. l-carnitine modulates glucose metabolism and enhances respiratory chain enzyme activity. Furthermore, it acts as an antioxidant to prevent oxidative damage and inhibit apoptosis, a signal in response to oxidative stress. Results show the potential of l-carnitine as a potential agent in assisted reproductive technology to improve oocyte quality and the subsequent embryonic development.