Key Enzymes Of Glucose Metabolism Research Articles

Fomentariol, a Fomes fomentarius Compound, Exhibits Anti-Diabetic Effects in Fungal Material: An In Vitro Analysis

The present study screened various fungal species for inhibitors of alpha-glucosidase, alpha-amylase, and DPP-4, enzymes that are crucial in carbohydrate metabolism. Ethanolic extracts exhibited superior inhibitory activity compared to water extracts, suggesting their potential as sources of anti-diabetic agents. Further fractionation revealed fomentariol from Fomes fomentarius as a potent inhibitor of alpha-glucosidase and DPP-4, with higher activity against alpha-glucosidase than acarbose. Fomentariol presents a novel avenue for diabetes management, demonstrating the simultaneous inhibition of key enzymes in glucose metabolism. However, comprehensive clinical studies are needed to evaluate its safety and efficacy in humans.

Regulation of macrophage polarization and glucose metabolism by the ERK/MAPK-HK1 signaling pathway in paraquat-induced acute lung injury

Acute lung injury is the leading cause of paraquat (PQ) poisoning-related mortality. The mechanism by which macrophages are involved in PQ-induced acute lung injury remains unclear. In recent years, the role of metabolic reprogramming in macrophage functional transformation has received significant attention. The current study aimed to identify the role of altered macrophage glucose metabolism and molecular mechanisms in PQ poisoning-induced acute lung injury. We established a model of acute lung injury in PQ-intoxicated mice via the intraperitoneal injection of PQ. PQ exposure induces macrophage M1 polarization and promotes the release of inflammatory factors, which causes the development of acute lung injury in mice. In vitro analysis revealed that PQ altered glucose metabolism, which could be reversed by siRNA transfection to silence the expression of HK1, a key enzyme in glucose metabolism. RNA sequencing revealed that the ERK/MAPK pathway was the crucial molecular mechanism of PQ pathogenesis. Further, U0126, an ERK inhibitor, could inhibit PQ-induced HK1 activation and macrophage M1 polarization. These findings provide novel insights into the previously unrecognized mechanism of ERK/MAPK-HK1 activation in PQ poisoning.

Analysis of sugar components and identification of SPS genes in citrus fruit development.

Sugar is a primary determinant of citrus fruit flavour, but undergoes varied accumulation processes across different citrus varieties owing to high genetic variability. Sucrose phosphate synthase (SPS), a key enzyme in glucose metabolism, plays a crucial role in this context. Despite its significance, there is limited research on sugar component quality and the expression and regulatory prediction of SPS genes during citrus fruit development. Therefore, we analysed the sugar quality formation process in 'Kiyomi' and 'Succosa', two citrus varieties, and performed a comprehensive genome-wide analysis of citrus CsSPSs. We observed that the accumulation of sugar components significantly differs between the two varieties, with the identification of four CsSPSs in citrus. CsSPS sequences were highly conserved, featuring typical SPS protein domains. Expression analysis revealed a positive correlation between CsSPS expression and sugar accumulation in citrus fruits. However, CsSPS expression displays specificity to different citrus tissues and varieties. Transcriptome co-expression network analysis suggests the involvement of multiple transcription factors in shaping citrus fruit sugar quality through the regulation of CsSPSs. Notably, the expression levels of four CsWRKYs (CsWRKY2, CsWRKY20, CsWRKY28, CsWRKY32), were significantly positively correlated with CsSPSs and CsWRKY20 might can activate sugar accumulation in citrus fruit through CsSPS2. Collectively, we further emphasize the potential importance of CsWRKYs in citrus sugar metabolism, our findings serve as a reference for understanding sugar component formation and predicting CsSPS expression and regulation during citrus fruit development.

Huangqi-Danshen decoction reshapes renal glucose metabolism profiles that delays chronic kidney disease progression

Huangqi-Danshen decoction (HDD), a Chinese herbal preparation, is effective in clinical treatment of chronic kidney disease (CKD). However, the underlying mechanism remains to be clarified. In this study, we aimed to investigate the role of HDD in the regulation of renal glucose metabolism in a CKD mouse model. The 0.2% adenine-induced CKD mouse model was administered HDD extract at a dose of 6.8 g/kg/day for 4 weeks. Detection of renal glucose metabolites was performed by ultra-performance liquid chromatography-tandem mass spectrometry. The expression of renal fibrosis and glucose metabolism-related proteins was tested by Western blotting, immunohistochemistry, and immunofluorescence. The results showed that HDD treatment could significantly reduce serum creatinine (0.36 ± 0.10 mg/dL vs. 0.51 ± 0.07 mg/dL, P < 0.05) and blood urea nitrogen (40.02 ± 3.73 mg/dL vs. 62.91 ± 10 mg/dL, P < 0.001) levels, and improve renal pathological injury and fibrosis. Aberrant glucose metabolism was found in the kidneys of CKD mice, manifested by enhanced glycolysis and pentose phosphate pathway, and tricarboxylic acid cycle inhibition, which could be partially restored by HDD treatment. Furthermore, HDD regulated the expression of hexokinase 2, phosphofructokinase, pyruvate kinase M2, pyruvate dehydrogenase E1, oxoglutarate dehydrogenase, and glucose-6-phosphate dehydrogenase in CKD mice. In conclusion, HDD protected against adenine-induced CKD, reshaped glucose metabolism profiles, and restored the expression of key enzymes of glucose metabolism in the kidneys of CKD mice. This study sheds light on targeting glucose metabolism for the treatment of CKD and screening small molecule compounds from herbal medicine to slow CKD progression.

Unearthing of the Antidiabetic Potential of Aqueous Extract of Solanum betaceum Cav. Leaves.

Solanum betaceum Cav., commonly known as tamarillo or Brazilian tomato, belongs to the Solanaceae family. Its fruit is used in traditional medicine and food crops due to its health benefits. Despite the numerous studies involving the fruit, there is no scientific knowledge about the tamarillo tree leaves. In this work, the phenolic profile of aqueous extract obtained from S. betaceum leaves was unveiled for the first time. Five hydroxycinnamic phenolic acids were identified and quantified, including 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, chlorogenic acid, caffeic acid and rosmarinic acid. While the extract displayed no effect on α-amylase, the extract inhibited the activity of α-glucosidase (IC50 = 1617 mg/mL), and it was particularly effective for human aldose reductase (IC50 = 0.236 mg/mL): a key enzyme in glucose metabolism. Moreover, the extract exhibited interesting antioxidant properties, such as a potent capacity to intercept the in vitro-generated reactive species O2•- (IC50 = 0.119 mg/mL) and •NO (IC50 = 0.299 mg/mL), as well as to inhibit the first stages of lipid peroxidation (IC50 = 0.080 mg/mL). This study highlights the biological potential of S. betaceum leaves. The scarcity of research on this natural resource underscores the need for additional studies in order to fully explore its antidiabetic properties and to promote the value of a species currently at risk of extinction.

Discovery of Novel Thiazolidinedione-Derivatives with Multi-Modal Antidiabetic Activities In Vitro and In Silico.

Diabetes mellitus (DM) and related complications continue to exert a significant burden on health care systems globally. Although conventional pharmacological therapies are beneficial in the management of this metabolic condition, it is still necessary to seek novel potential molecules for its management. On this basis, we have synthesised and evaluated the anti-diabetic properties of four novel thiazolidinedione (TZD)-derivatives. The TZD derivatives were synthesised through the pharmacophore hybridisation strategy based on N-arylpyrrole and TZD. The resultant derivatives at different concentrations were screened against key enzymes of glucose metabolism and glucose utilisation in the liver (HEP-G2) cell line. Additionally, peroxisome proliferator-activated receptor-γ activation was performed through docking studies. Docking of these molecules against PPAR-γ predicted strong binding, similar to that of rosiglitazone. Hence, TZDD2 was able to increase glucose uptake in the liver cells as compared to the control. The enzymatic inhibition assays showed a relative inhibition activity; with all four derivatives exhibiting ≥ 50% inhibition activity in the α-amylase inhibition assay and a concentration dependent activity in the α-glucosidase inhibition assay. All four derivatives exhibited ≥30% inhibition in the aldose reductase inhibition assay, except TZDD1 at 10 µg/mL. Interestingly, TZDD3 showed a decreasing inhibition activity. In the dipeptidyl peptidase-4 inhibition assay, TZDD2 and TZDD4 exhibited ≥20% inhibition activity.

Expression of Key Enzymes in Glucose Metabolism in Chronic Mountain Sickness and Its Correlation with Phenotype

To explore the pathogenesis of erythrocytosis by detecting the key enzymes of glucose metabolism and glucose transporter in bone marrow erythrocytes of chronic mountain sickness (CMS), and analyzing its correlation with hemoglobin. Twenty CMS patients hospitalized in Qinghai Provincial People's Hospital from January 2019 to December 2020 were selected as CMS group. Twenty males with leukocyte count > 3.5×109/L who had accepted bone marrow aspiration and had normal result were taken as control group. The mRNA and protein expression of key enzymes and glucose transporter in glucose metabolism in bone marrow CD71+ erythrocytes were detected by real time qPCR and Western blot, respectively. Glucose, lactic acid and 2,3-diphosphoglycerate in the bone marrow supernatant and serum were tested by ELISA. The mRNA and protein expression of key enzymes and glucose transporter, glucose, lactic acid and 2,3-diphosphoglycerate of the two groups were compared. Pearson correlation was used to analyze the correlation between key enzymes, glucose transporter in glucose metabolism in bone marrow CD71+ erythrocytes and hemoglobin. The expression of HK2, GLUT1 and GLUT2 mRNA in the CMS group were higher than those in the control group (P<0.001), while the expression of HK1, OGDH and COX5B mRNA were not different. The expression of HK2, GLUT1 and GLUT2 protein in the CMS group were higher than those in the control group (P<0.05). The levels of glucose and lactic acid in the bone marrow supernatant and serum in the CMS group were not different from those in the control group, while the level of 2,3-diphosphoglycerate was higher (P<0.001). Both HK2 and GLUT2 proteins were positively correlated with hemoglobin (r=0.511, 0.717). CMS patients may increase glycolysis by increasing the expression of HK2, and promote the utilization of glucose through high expression of GLUT1 and GLUT2 to meet the need of energy supply.

Microglial metabolic reconfiguration provides a new strategy for the treatment of Alzheimer's disease.

Microglial metabolic reconfiguration provides a new strategy for the treatment of Alzheimer's disease.

Oxidative stress-induced alterations in retinal glucose metabolism in Retinitis Pigmentosa

Retinitis pigmentosa occurs due to mutations that cause rod photoreceptor degeneration. Once most rods are lost, gradual degeneration of cone photoreceptors occurs. Oxidative damage and abnormal glucose metabolism have been implicated as contributors to cone photoreceptor death. Herein, we show increased phosphorylation of key enzymes of glucose metabolism in the retinas of rd10 mice, a model of RP, and retinas of wild type mice with paraquat-induced oxidative stress, thereby inhibiting these key enzymes. Dietary supplementation with glucose and pyruvate failed to overcome the inhibition, but increased reducing equivalents in the retina and improved cone function and survival. Dichloroacetate reversed the increased phosphorylation of pyruvate dehydrogenase in rd10 retina and increased histone acetylation and levels of TP53-induced glycolysis and apoptosis regulator (TIGAR), which redirected glucose metabolism toward the pentose phosphate pathway. These data indicate that oxidative stress induced damage can be reversed by shifting glycolytic intermediates toward the pentose phosphate pathway which increases reducing equivalents and provides photoreceptor protection.

Adding value to marine invaders by exploring the potential of Sargassum muticum (Yendo) Fensholt phlorotannin extract on targets underlying metabolic changes in diabetes

Marine biological invasions have considerable ecological and economic impact, and despite the attempts to control their spread, none has proved effective. Among seaweeds, Sargassum muticum (Yendo) Fensholt is recognized as one of the most successful invader species. If, on the one hand, S. muticum invasions are a potential threat to the marine environment, they can also arise as a valuable opportunity for obtaining unique bioactive compounds. While displaying a very mild inhibition towards α-amylase (IC50 > 5000 μg mL−1), phlorotannin-targeted S. muticum extract was particularly effective for α-glucosidase (IC50 = 27.06 μg mL−1), acting as a mixed-type inhibitor, and inhibited the activity of human aldose reductase (IC50 = 1345.85 μg mL−1), a key-enzyme in glucose metabolism. Moreover, the extract exhibited antiglycative effects and antioxidant properties, the latter being suggested as responsible for preventing macrophage-mediated injury. This work harnesses the biotechnological potential of S. muticum biomass, upholding the functionality of its polyphenolic constituents in the emergent interlink between diabetes, oxidative stress and inflammation.

Advances in the role of silence information regulator family in pathological pregnancy.

Aberrant maternal inflammation and oxidative stress are the two main mechanisms of pathological pregnancy. The silence information regulator (sirtuin) family is a highly conserved family of nicotinamide adenine dinucleotide (NAD)-dependent deacylases. By regulating the post-translational modification of proteins, sirtuin is involved in various biological processes including oxidative stress and inflammation. Nowadays, emerging evidence indicates that sirtuin may be closely related to the occurrence and development of pathological pregnancy. The down-regulation of sirtuin can cause spontaneous preterm delivery by promoting uterine contraction and rupture of fetal membranes, cause gestational diabetes mellitus through promoting oxidative stress and affecting the activity of key enzymes in glucose metabolism, cause preeclampsia by reducing the proliferation and invasion ability of trophoblasts, cause intrahepatic cholestasis of pregnancy by promoting the production of bile acids and T helper 1 cell (Th1) cytokines, and cause intrauterine growth restriction through inducing mitochondrial dysfunction. Moreover, the expression and activation of sirtuin can be modulated through dietary interventions, thus sirtuin is expected to become a new target for the prevention and treatment of pregnancy complications. This article reviews the role of the sirtuin family in the occurrence and development of pathological pregnancy and its influence on the development of the offspring.

Research progress in the role and mechanism of polysaccharides in regulating glucose and lipid metabolism

Polysaccharides are a group of compounds composed of multiple monosaccharides of the same or different structures combined by glycosidic bonds, and are widely found in animals and plants and in the cell walls of microorganisms. Polysaccharides possess the advantages of high safety and low toxicity. Recent studies revealed that polysaccharides have a wide range of biological activities including immunoregulation, anti-tumor, antiviral, antioxidant activities, and blood glucose-and lipid- lowering effects. The effects of polysaccharides in improving insulin sensitivity and regulating glucose and lipid metabolism have drawn much attention from researchers. Many polysaccharides can reduce blood glucose and blood lipid by repairing pancreatic islet cells, improving insulin resistance, regulating intestinal flora, enhancing antioxidant capacity, and regulating the activities of key enzymes in glucose and lipid metabolism. This reviews examines the role and mechanism of polysaccharides in regulating glucose and lipid metabolism. The mechanisms of polysaccharide in regulating glucose metabolism include repairing islet cells and increasing insulin content, increasing insulin sensitivity and improving insulin resistance, regulating the activity of key enzymes in glucose metabolism, increasing synthesis of liver glycogen, and regulating intestinal flora. Polysaccharides can also regulate glucose metabolism by improving immune regulation and antagonizing glucagon. Polysaccharide also regulate lipid metabolism by regulating lipid absorption, expression of the related genes such as PPAR-α, enzyme activities in lipid metabolism, improving antioxidant capacity, and modulating intestinal flora and signaling pathways.

Modulation of insulin resistance by renin angiotensin system inhibitors: implications for cardiovascular prevention.

Insulin resistance (IR) and the related hyperinsulinamia play a key role in the genesis and progression of the continuum of cardiovascular (CV) disease. Thus, it is reasonable to pursue in primary and secondary CV prevention, the pharmacological strategies that are capable to interfere with the development of IR. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of IR. In particular, angiotensin II (Ang II) through the generation of reactive oxygen species, induces a low grade of inflammation, which impairs the insulin signal transduction. The angiotensin converting enzyme (ACE) inhibitors are effective not only as blood pressure-lowering agents, but also as modulators of metabolic abnormalities. Indeed, experimental evidence indicates that in animal models of IR, ACE inhibitors are capable to ameliorate the insulin sensitivity. The Ang II receptor blockers (ARBs) modulate the peroxisome proliferator-activated receptor (PPAR)-γ activity. PPARâ€"γ is a transcription factor that controls the gene expression of several key enzymes of glucose metabolism. A further mechanism that accounts for the favorable metabolic properties of ARBs is the capability to modulate the hypothalamicâ€"pituitary-adrenal (HPA) axis. The available clinical evidence is consistent with the concept that both ACE inhibitors and ARBs are able to interfere with the development of IR and its consequences like type 2 diabetes. In addition, pharmacological inhibition of the RAAS has favourable effects on dyslipidaemias, metabolic syndrome and obesity. Therefore, the pharmacological antagonism of the RAAS, nowadays, represents the first choice in the prevention of cardio-metabolic diseases.

Effect of Increased IL-1β on Expression of HK in Alzheimer's Disease.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by decreased glucose metabolism and increased neuroinflammation. Hexokinase (HK) is the key enzyme of glucose metabolism and is associated with mitochondria to exert its function. Recent studies have demonstrated that the dissociation of HK from mitochondria is enough to activate the NOD-like receptor protein 3 (NLRP3) inflammasome and leads to the release of interleukin-1β (IL-1β). However, the effect of increased IL-1β on the expression of HK is still unclear in AD. In this paper, we used positron emission tomography (PET), Western blotting and immunofluorescence to study the glucose metabolism, and the expression and distribution of HK in AD. Furthermore, we used lipopolysaccharide (LPS), nigericin (Nig), CY-09 and lonidamine (LND) to treat N2a and N2a-sw cells to investigate the link between IL-1β and HK in AD. The results show decreased expression of HK and the dissociation of HK from mitochondria in AD. Furthermore, a reduction of the expression of IL-1β could increase the expression of HK in AD. These results suggest that inhibiting inflammation may help to restore glucose metabolism in AD.

Reprogramming of aerobic glycolysis in non-transformed mouse liver with pyruvate dehydrogenase complex deficiency.

The Pyruvate Dehydrogenase Complex (PDC), a key enzyme in glucose metabolism, catalyzes an irreversible oxidative decarboxylation reaction of pyruvate to acetyl‐CoA, linking the cytosolic glycolytic pathway to mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. Earlier we reported a down‐regulation of several key hepatic lipogenic enzymes and their upstream regulators in liver‐specific PDC‐deficient mouse (L‐PDCKO model by deleting the Pdha1 gene). In this study we investigated gene expression profiles of key glycolytic enzymes and other proteins that respond to various metabolic stresses in liver from L‐PDCKO mice. Transcripts of several, such as hexokinase 2, phosphoglycerate kinase 1, pyruvate kinase muscle‐type 2, and lactate dehydrogenase B as well as those for the nonglycolysis‐related proteins, CD‐36, C/EBP homologous protein, and peroxisome proliferator‐activated receptor γ, were up‐regulated in L‐PDCKO liver whereas hypoxia‐induced factor‐1α, pyruvate dehydrogenase kinase 1 and Sirtuin 1 transcripts were down‐regulated. The protein levels of pyruvate kinase muscle‐type 2 and lactate dehydrogenase B were increased whereas that of lactate dehydrogenase A was decreased in PDC‐deficient mouse liver. Analysis of endoplasmic reticulum and oxidative stress indicators suggests that the L‐PDCKO liver showed evidence of the former but not the latter. These findings indicate that (i) liver‐specific PDC deficiency is sufficient to induce “aerobic glycolysis characteristic” in mouse liver, and (ii) the mechanism(s) responsible for these changes appears distinct from that which induces the Warburg effect in some cancer cells.

Launaea acanthodes (Boiss) O. Kuntze mediates hepatic glucose metabolism and ameliorates impaired pancreatic function in streptozotocin-induced diabetic rats

Ethnopharmacological relevanceLaunaea acanthodes (Boiss.) O. Kuntze is native to semiarid regions of central Iran, traditionally used in the treatment of numerous disorders including diabetes. Aim of the studyThe current study aimed to explore hypoglycemic activity of Launaea acanthodes extract in streptozotocin-induced diabetic rats. Furthermore, gene expression study was carried out to examine expression levels of key glucose metabolism-related genes. MethodsFor in vitro study, Folin-Ciocalteus, DPPH and aluminum chloride colorimetric assays were used to determine the total phenolic content, antioxidant capacity and total flavonoid content of extracts, respectively. For in vivo study, streptozotocin-induced diabetic Wistar rats were orally administered with metformin (50 mg/kg) and various doses of extracts (100, 200 and 400 mg/kg body weight) for 28 days. Fasting blood glucose, body weight, food and water intake were assessed during the course of treatment. At the end of the intervention, oral glucose tolerance test (OGTT), lipid profile and glycated hemoglobin (HbA1c) were evaluated. Furthermore, functional liver enzymes, oxidative stress markers and histopathology of pancreas were examined. Lastly, quantitative real time polymerase chain reaction (qRT-PCR) was applied to explore the mRNA levels of genes relevant to glucose metabolism in the pancreas and liver tissues of diabetic rats. ResultsBased on the in vitro results, the hydroalcoholic extract revealed potential radical scavenging activity and contained highest amount of phenolic and flavonoid. The in vivo results demonstrated that the extract lowered fasting blood glucose level, increased the body weight, restored the alterations in the levels of water and food intake, attenuated HbA1c, improved lipid profile and ameliorated the OGTT in diabetic rats. The extract administration alleviated the histopathological changes in the pancreas, suppressed malondialdehyde (MDA) level and further restored attenuated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in diabetic rats. Analysis of real time PCR data showed that extract administration reversed the expression levels of hepatic glucokinase (GK), phosphenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Meanwhile, the extract upregulated the expression level of glucose transporter-2 (GLUT-2) and pancreatic-duodenal homeobox (PDX-1) in diabetic rats. ConclusionCollectively, the results demonstrate that Launaea acanthodes hydroalcoholic extract exerts hypoglycemic effect possibly via regulating key enzymes of glucose metabolism and ameliorating pancreatic dysfunction through its antioxidant properties.

C18:1 Improves the Freeze-Drying Resistance of Lactobacillus plantarum by Maintaining the Cell Membrane.

Increasing knowledge about lactic acid bacteria as fermentation starters and probiotics to improve health has led to a growing awareness of their application potential. Despite a long history of applying cryoprotectants, the maintenance of probiotic viability is still a major challenge. In this study, we implemented a strategy and explored its mechanisms in detail. We found that the survival rates after freeze-drying were positively correlated with the relative concentration of the octadecenoic acid (C18:1) and with the ratio of unsaturated to saturated FAs (U/S ratio). The addition of C18:1 significantly improved the survival of L. plantarum after freeze-drying. Contrary to the most commonly used cryoprotectants, the addition of C18:1 did not affect the glass transition temperature or collapse temperature. We predicted that the cell membrane characteristics would be significantly degraded during the drying stage, but C18:1 can effectively maintain the cell membrane integrity and fluidity. Our experiments confirmed those predictions, and simultaneously found that the enzyme activities of key enzymes of glucose metabolism were increased compared with the control group. These finding indicate that C18:1 might serve as a lyoprotectant to maintain the cell membrane integrity and fluidity, and thereby increasing the survival rate of L. plantarum after freeze-drying. This study constitutes a strategy to safeguard bacterial viability.

Inhibition of GSK-3β activity suppresses HCC malignant phenotype by inhibiting glycolysis via activating AMPK/mTOR signaling.

Glycogen synthase kinase-3 beta (GSK-3β) has been shown to play a critical role in the development of many cancers, but its role in hepatocellular carcinoma (HCC) remains unclear. Deregulating cellular energetics is a signature hallmark of cancer, therefore modulating cancer metabolism has become an attractive anti-cancer approach in recent years. As a key enzyme in glucose metabolism, understanding the role of GSK-3β in cancer metabolic process may facilitate the development of effective therapeutic approach for HCC. In this study, we showed that inhibition of GSK-3β led to diminished viability, metastasis and tumorigenicity in HCC cells. Suppression of GSK-3β activity also reduced glucose consumption, lactate production and adenosine triphosphate (ATP) levels in HCC cells. The decreased extracellular acidification rate (ECAR) and down-regulated key enzymes on the glycolysis pathway by GSK3β inhibition demonstrated that GSK-3β was involved in glycolysis process of HCC. Mechanistically, the metabolic change and anti-cancer effect by GSK-3β inhibition was achieved mainly through activation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, which negatively affected glycolysis and cell proliferation. The results from primary HCC cells and from in vivo nude mice model confirmed our observations. Our study results indicated that GSK-3β may become a promising therapeutic target for HCC.

Modulatory effect of isopulegol on hepatic key enzymes of glucose metabolism in high-fat diet/streptozotocin-induced diabetic rats

To investigate the antidiabetic effect of isopulegol in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Animals were made diabetic by feeding HFD for 4 weeks followed by single intraperitoneal injection of STZ (35 mg/kg b.w.; 0.1 M citrate buffer; pH 4.0). Plasma insulin, haemoglobin and glycogen content were decreased while increased glucose and glycated haemoglobin were observed in diabetic rats. An increase in glucose-6-phosphatase, fructose-1,6-bisphosphatase, phosphoenol pyruvate carboxykinase with a decrease in hexokinase, glucose-6-phosphate dehydrogenase and glycogen synthase activities was observed in diabetic rats. The expression of cyclic response element binding protein (CREB) was increased in the hepatic tissue of diabetic rats. Isopulegol dose dependently (50, 100 and 200 mg/kg b.w.) improved insulin secretion, glucose tolerance and decreased glucose levels in diabetic-treated rats. At the effective dose of 100 mg/kg b.w., isopulegol restored the activities of metabolic enzymes and down-regulated CREB expression. Thus, isopulegol restored glucose homeostasis through its insulinotrophic property.

Effects of citral on oxidative stress and hepatic key enzymes of glucose metabolism in streptozotocin/high-fat-diet induced diabetic dyslipidemic rats.

Objective(s):Phytochemicals such as polyphenols, alkaloids, and terpenoids, protect against the development of early stages and complications of diabetes mellitus according to various reports. The aim of this study was to measure the anti-dyslipidemic and anti-diabetic effects of Citral on high-fat-diet (HFD) and streptozotocin (STZ) induced diabetic dyslipidemic rats and to see also its effect on carbohydrate metabolic regulatory enzymes in the liver. Materials and Methods:Rats were kept on a high-fat diet for 2 weeks, then diabetes was induced by a single dose of STZ (35 mg/kg/BW, intraperitoneally), Citral was administered orally at a dose of 45 mg/kg/BW for 28 days to diabetic rats. Blood glucose, plasma insulin, and lipid profile in blood were studied. Antioxidant activities were assayed in the liver, pancreas, and adipose tissues. Carbohydrate metabolic enzymes of the liver were also studied in diabetic dyslipidemic rats.Results:The results of this study confirmed that administration of Citral significantly (P<0.05) decreased the blood glucose level and increased plasma insulin in diabetic rats. Citral also improved oxidative markers along with anti-oxidative enzymes of the liver, adipose tissue, and pancreas in the HFD/STZ group. Citral also regulated the activity of the glucose-metabolic enzymes in the liver. The results of the present study were compared to Glibenclamide, which is a standard oral drug for lowering the blood sugar. Conclusion:Results may show that Citral possesses anti-dyslipidemic activity as well as anti-diabetic activity and also regulates the enzyme activity of glycolytic and gluconeogenic processes in the liver.