Key Enzymes Of Carbohydrate Metabolism Research Articles

Hesperetin-loaded chitosan nanoparticles ameliorate hyperglycemia by regulating key enzymes of carbohydrate metabolism in a diabetic rat model.

The study aimed to investigate the potential of hesperetin-loaded chitosan nanoparticles (HSPCNPs) in alleviating hyperglycemia by modulating key enzymes in diabetic rats. Chitosan nanoparticles loaded with hesperetin were prepared using the ionic gelation method and characterized with Electron microscope (SEM), zeta potential, particle size analysis, Fourier-transform infrared (FT-IR), Energy dispersive spectroscopy (EDS) and Encapsulation efficiency and Loading efficiency. To induce diabetes, rats were fed a high-fat beef tallow diet for 28 days, then given a single dose of streptozotocin (STZ) at 35 mg/kg b.w in 0.1 M citrate buffer (pH 4.0). Rats were treated with HSPCNPs at doses of 10, 20, and 40 mg/kg b.w. The analyzed parameters included body weight, food and water intake, plasma glucose and insulin, liver and skeletal muscle glycogen levels, and carbohydrate metabolism. SEM imaging revealed dimensions between 124.2and 251.6 nm and a mean particle size of 145.0 nm. FT-IR analysis confirmed the presence of functional groups in the chitosan nanoparticles, and the zeta potential was 35.5 mV. HSPCNP 40 mg/kg b.w significantly (p < 0.05) reduced blood glucose levels and glycosylated hemoglobin, improving body weight, food intake, and reducing water intake. In diabetic rats, enzymes for carbohydrate metabolism like fructose 1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose 6-phosphatase are evaluated in the liver, while glucose 6 phosphate dehydrogenase and hexokinase activity were significantly lower. Additionally, plasma insulin levels increased, indicating enhanced insulin sensitivity. The results show that HSPCNPs at 40 mg/kg b.w. ameliorate hyperglycemiato provide robust protection against diabetic complications and significantly improve metabolic health.

DFT study of sucrose hydrolysis by a GH32 cell-wall invertase, a key enzyme in carbohydrate metabolism

ABSTRACT The Arabidopsis thaliana cell-wall invertase 1 (AtCWIN1), a member of the family 32 glycoside hydrolase (GH32), hydrolyzes sucrose into fructose and glucose via a retaining mechanism. AtCWIN1 plays a key role in sucrose metabolism in plant. Here, the reaction mechanism of the GH32 AtCWIN1 enzyme has been investigated using quantum chemical approach. Two alternative orientations of an acid/base catalyst (Glu203) with regard to the location of the pK a modulators (Arg148 and Tyr279) are investigated to understand the involvement of these pK a residues in the reaction. The calculations suggested that the orientation involving a hydrogen bond network (Arg148•••Glu203•••Tyr279) is energetically more favourable than the other (Arg148•••Glu203), with a barrier of 17.5 kcal mol−1, which is consistent with the experimental value (15.3 kcal/mol). This Arg148•••Glu203•••Tyr279 interaction provides a strong H-bond network that stabilises the reaction effectively. Overall, this study demonstrates that the enzymatic activity in AtCWIN1 depends on a hydrogen bond network created by the residues Arg148, Glu203, and Tyr279.

Syringic Acid Alleviates Hyperglycemia by Regulating Hepatic Key Enzymes of Carbohydrate Metabolism in Streptozotocin-induced Diabetic Rats

Background: Diabetes mellitus is a complex metabolic disorder characterized by the development of hyperglycemia due to impaired insulin production, insulin action, or both. The persistent hyperglycemia associated with diabetes can lead to an increased risk of developing severe health problems. This study examines whether the bioactive phenolic compound Syringic Acid (SA) mitigates hyperglycemia in streptozotocin-induced diabetic rats. Materials and Methods: A total of 30 male Sprague-Dawley rats were utilized in the investigation, and they were split into five groups: Normal (N), Normal+Syringic Acid (N+SA), Diabetic Control (DC), Diabetic+Syringic Acid (D+SA), and Diabetic+Glimepiride (D+GM). A single dose of streptozotocin (40 mg/kg) injected intraperitoneally was used to induce diabetes. Syringic Acid (SA) was given orally once a day for 60 days at a dose of 50 mg/Kg body weight. The levels of plasma insulin, glucose, glycated haemoglobin, and the activity of carbohydrate metabolizing enzymes were examined. Results were compared with diabetic rats provided with the standard drug glimepiride (0.1 mg/kg). Results: Syringic acid treatment substantially lowered hyperglycemia, enhanced insulin levels, and lowered HbA1c, in diabetic rats when given at a dose of 50 mg/Kg body weight. Additionally, syringic acid exhibited the ability to considerably lower the activities of fructose 1,6-bisphosphatase and glucose-6 phosphatase while significantly increasing the activities of glycolytic enzymes like pyruvate kinase and hexokinase. Conclusion: These results imply that syringic acid could potentially attenuate hyperglycemia in streptozotocin-induced diabetic rats by modulating carbohydrate metabolism.

Flavonoids by Ultrasonic-Assisted Extraction from Herbal Formulation of Zingiber officinale, Portulaca oleracea, and Tamarindus indica Improved Type 2 Diabetes in C57BL6/J Mice

Background: Diabetes is a problem of public health, in consequence, the increasing prevalence of both diseases needs more functional food products with efficiency and low cost to support treatment. Methods: Flavonoids from the herbal formulation of Portulaca oleracea, Zingiber officinale, and Tamarindus indica were extracted by ultrasound-assisted extraction technology, where several experiments were conducted to determine the implication of three independent variables on the higher production of flavonoids. Extraction time, ethanol concentration, and the liquid-solid ratio were determined as optimal conditions. Furthermore, flavonoids of interest in the extract were determined by using HPLC with UV/vis and mass spectrum and direct comparison reference compounds. Then was determined and compared the effect of extracts from P. oleracea (P), Z. officinale (Z), T. indica (T), and its combination (PTZ) on high-fat-diet-induced diabetic C57BL6/J mice. Results: The optimum conditions provided by the model include an extraction time of 30 min, an ethanol concentration of 50%, and a liquid/solid ratio of 40:1 mL/g, The antidiabetic effect of an extract rich in polyphenolic compounds was evaluated using streptozotocin (STZ) and a high-fat diet-induced diabetic mouse. Effect of extracts on high-fat-diet-induced diabetic mice including decreased FER, improved insulin sensitivity, fasting blood glucose, and serum lipid, and shown reducing body weight gain associated with a reduction of food intake. Extracts have protective effects on kidneys and liver improve lipolysis and successively decrease adipose tissue. Treatment with the polyherbal mixture has shown no toxic effects, possesses potent antihyperlipidemic, antihyperglycemic effects, and decreased glycated hemoglobin. The serum insulin level was significantly increased (p &lt; 0.05) on the polyherbal extract treatment, supporting the evidence of β-cell re-establishment in the pancreas. reduce body weight and food intake, plasma adiponectin level increased while serum leptin level was significantly reduced compared with the HFD group. In addition, the activities of key enzymes of carbohydrate metabolism, antioxidant enzymes, lipid peroxidation markers, and glycogen content were also improved in diabetic mice. Conclusion: The combined form of P. oleracea, Z. officinale, and T. indica had better anti-diabetic properties compared to a single therapy, especially which could be related to their high content of phytochemicals in comparison with the bioactive content of a single plant. The results presented here indicated that the use of PTZ due to their synergistic effects can be useful against diabetes improving the factors associated with this disease.

Tomato growth promotion by the fungal endophytes Serendipita indica and Serendipita herbamans is associated with sucrose de-novo synthesis in roots and differential local and systemic effects on carbohydrate metabolisms and gene expression

Plant growth-promoting and stress resilience-inducing root endophytic fungi represent an additional carbohydrate sink. This study aims to test if such root endophytes affect the sugar metabolism of the host plant to divert the flow of resources for their purposes. Fresh and dry weights of roots and shoots of tomato (Solanum lycopersicum) colonised by the closely related Serendipita indica and Serendipita herbamans were recorded. Plant carbohydrate metabolism was analysed by measuring sugar levels, by determining activity signatures of key enzymes of carbohydrate metabolism, and by quantifying mRNA levels of genes involved in sugar transport and turnover. During the interaction with the tomato plants, both fungi promoted root growth and shifted shoot biomass from stem to leaf tissues, resulting in increased leaf size. A common effect induced by both fungi was the inhibition of phosphofructokinase (PFK) in roots and leaves. This glycolytic-pacing enzyme shows how the glycolysis rate is reduced in plants and, eventually, how sugars are allocated to different tissues. Sucrose phosphate synthase (SPS) activity was strongly induced in colonised roots. This was accompanied by increased SPS-A1 gene expression in S. herbamans-colonised roots and by increased sucrose amounts in roots colonised by S. indica. Other enzyme activities were barely affected by S. indica, but mainly induced in leaves of S. herbamans-colonised plants and decreased in roots. This study suggests that two closely related root endophytic fungi differentially influence plant carbohydrate metabolism locally and systemically, but both induce a similar increase in plant biomass. Notably, both fungal endophytes induce an increase in SPS activity and, in the case of S. indica, sucrose resynthesis in roots. In leaves of S. indica-colonised plants, SWEET11b expression was enhanced, thus we assume that excess sucrose was exported by this transporter to the roots. ‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬

In Vitro Combined Effect of Annona Senegalensis and Piliostigma Thonningii Leaf Extracts on Alpha Amylase Activity

Background: Diabetes mellitus (DM), a group of metabolic disorders characterised by hyperglycaemia, has been attributed to increased activity of α-amylase, one of the key enzymes in carbohydrate metabolism. Alpha amylase inhibition can potentially control postprandial hyperglycaemia, hence significant in the management of diabetes mellitus, especially type 2. Acarbose, the proven α-amylase inhibitor, has been associated with several side effects. Plants used in traditional medicine represent a valuable source in the search for an alternative. The study aimed at determining the combined effect of Piliostigma thonningii and Annona senegalensis leaf extracts on alpha amylase activity. Methodology: Mortar and pestle were used to crush the leaves into powder. The fine powder was dispensed in distilled water. Percolation was used to filter the crude extract, evaporated in a water bath at 65 0C to concentrate the extract then reconstituted. Spectrophotometric assay method was used for alpha amylase activity at 540 nm. Results: The results of the study showed that A. senegalensis inhibited α-amylase by 27%, 32% and 34% at 15, 30 and 45 minutes respectively. P. thonningii exhibited inhibitory effects on α-amylase by 25%, 27% and 37% at 15, 30 and 45 minutes respectively. The combined inhibitory effects of A. senegalensis and P. thonningii on α-amylase were 28%, 37% and 62% at 15, 30 and 45 minutes respectively which are significantly different (p &lt;0.05) from that of the positive control, acarbose (71% at 45 minutes) Conclusion: This study revealed the increased strength to inhibit alpha amylase enzyme by a combination of A. senegalensis and P. thonningii and a proportional increase in the inhibitory effect with increase in incubation time than their individual potential to inhibit alpha amylase.

A novel in vitro approach to test the effectiveness of fish oil in ameliorating type 1 diabetes.

Diabetes type 1 (T1D) characterized by destruction of pancreatic β-cells results in inadequate insulin production and hyperglycaemia.Generation of reactive oxygen species and glycosylation end-products stimulates toxic impacts on T1D. Dietary w-3 fatty acids present in Fish oil (FO) might be helpful in the prevention of oxidative stress and lipid peroxidation, thus, beneficial against T1D. But how the cellular secretion from β-cells under influence of FO affects the glucose homeostasis of peri-pancreatic cells is poorly understood. In the current study, we aimed to introduce anin vitromodel for T1D and evaluate its effectiveness in respect of alloxan treatment to pancreatic Min6 cells. We use alloxan in the Min6 pancreatic β-cell line to induce cellular damage related to T1D. Further treatment with FO was seen to prevent cell death by alloxan and induce mRNA expression of both insulin 1 and insulin 2 isoforms under low-glucose conditions. From the first part of the study, it is clear thatFO is effective to recover Min6 cells from the destructive effect of alloxan, and it worked best when given along with alloxan or given after alloxan treatment regime. FO-induced secretion of molecules from Min6 was clearly shown to regulate mRNA expression of key enzymes of carbohydrate metabolism in peri-pancreatic cell types. This is a pilot study showing that an improvedin vitroapproach of using Min6 along with muscle cells (C2C12) and adipose tissue cells (3T3-L1) together to understand the crosstalk of molecules could be used to check the efficacy of an anti-diabetic drug.

Glycogen Storage Disease Type Ia: Current Management Options, Burden and Unmet Needs.

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Dietary treatment has improved the prognosis for patients with GSDIa; however, the disease itself, its management and monitoring have significant physical, psychological and psychosocial burden on individuals and parents/caregivers. Hypoglycaemia risk persists if a single dose of UCCS is delayed/missed or in cases of gastrointestinal intolerance. UCCS therapy is imprecise, does not treat the cause of disease, may trigger secondary metabolic manifestations and may not prevent long-term complications. We review the importance of and challenges associated with achieving good glycaemic/metabolic control in individuals with GSDIa and how this should be balanced with age-specific psychosocial development towards independence, management of anxiety and preservation of quality of life (QoL). The unmet need for treatment strategies that address the cause of disease, restore glucose homeostasis, reduce the risk of hypoglycaemia/secondary metabolic perturbations and improve QoL is also discussed.

LXR and INSIG Act as Differentiators in the Regulation of the Gene Expression of G6PDH and FAS Under Insulin Resistant Conditions

Diabetes, a chronic metabolic disease that affects nearly 10% of the world's population can lead to very serious complications such as renal failure, liver cirrhosis, and heart attacks. The most common type is Type 2 diabetes and is diagnosed when a person has elevated amounts of blood glucose due to insulin resistance. This resistance to insulin leads to problems with glucose transport into tissues for subsequent metabolism. Over the years it has been shown that insulin regulates the expression of several key enzymes in both carbohydrate and fatty acid metabolic pathways via the phosphatidyl inositol 3-kinase (PI3K) pathway. Previously, using glucosamine, a precursor of the hexosamine biosynthetic pathway, we had established a model of insulin resistance in primary rat hepatocytes in culture. Using this primary cell culture model, we showed that under insulin resistant conditions, the expression of glucose 6 phosphate dehydrogenase (G6PDH), a key enzyme in carbohydrate metabolism and fatty acid synthase (FAS), a key enzyme in fat metabolism were differently regulated but the mechanism of this differentiation was unclear. Under this model of insulin resistance, we now show that this differential regulation is due to the liver X receptor (LXR) and insulin induced gene (INSIG).

Melatonin improves cognitive behavior, oxidative stress, and metabolism in tumor‐prone lethal giant larvae mutant of Drosophila melanogaster

Mutant lethal giant larvae (lgl) flies (Drosophila melanogaster) are known to develop epithelial tumors with invasive characteristics. The present study has been conducted to investigate the influence of melatonin (0.025 mM) on behavioral responses of lgl mutant flies as well as on biochemical indices (redox homeostasis, carbohydrate and lipid metabolism, transaminases, and minerals) in hemolymph, and head and intestinal tissues. Behavioral abnormalities were quantitatively observed in lgl flies but were found normalized among melatonin-treated lgl flies. Significantly decreased levels of lipid peroxidation products and antioxidants involved in redox homeostasis were observed in hemolymph and tissues of lgl flies, but had restored close to normalcy in melatonin-treated flies. Carbohydrates including glucose, trehalose, and glycogen were decreased and increased in the hemolymph and tissues of lgl and melatonin-treated lgl flies, respectively. Key enzymes of carbohydrate metabolism showed a significant increment in their levels in lgl mutants but had restored close to wild-type baseline levels in melatonin-treated flies. Variables of lipid metabolism showed significantly inverse levels in hemolymph and tissues of lgl flies, while normalization of most of these variables was observed in melatonin-treated mutants. Lipase, chitinase, transaminases, and alkaline phosphatase showed an increment in their activities and minerals exhibited decrement in lgl flies; reversal of changes was observed under melatonin treatment. The impairment of cognition, disturbance of redox homeostasis and metabolic reprogramming in lgl flies, and restoration of normalcy in all these cellular and behavioral processes indicate that melatonin could act as oncostatic and cytoprotective agents in Drosophila.

Enzymatic and transcriptomic analysis reveals the essential role of carbohydrate metabolism in freesia (Freesia hybrida) corm formation

Starch and sucrose metabolism plays a crucial role in the formation and development of bulbs in bulbous plants. However, these mechanisms remain unclear and unexplored in the corms of Freesia hybrida. Herein, we investigated the dynamics of the major form of carbohydrates and related enzyme activities and profiled the transcriptome of freesia corms at four developmental stages with the aim to reveal the relation between the expression of genes involved in the metabolism of carbohydrates and the accumulation of carbohydrates in corm developmental stages for further exploring the mechanism on the starch and sucrose metabolism regulating the formation and development of corms in F. hybrida. The content of starch, sucrose and soluble sugars followed an overall upward trend across the corm developmental stages. Activities of the adenosine diphosphoglucose pyrophosphorylase, starch branching enzyme and β-amylase generally followed the pattern of the starch and sucrose levels. Activities of sucrose phosphate synthase increased from corm formation till the initial swelling stage and subsequently reached a plateau. Activities of invertase and sucrose synthase peaked at the later rapid swelling stage. These suggested that the starch and sucrose dynamics paralleled corm swelling under the action of metabolic enzymes. A total of 100,999 unigenes were assembled in the transcriptomic analysis, and 44,405 unigenes of them were annotated. Analysis based on Clusters of Orthologous Groups suggested that carbohydrate transport and metabolism (9.34% of the sequences) was prominent across the corm developmental process. In total 3,427 differentially expressed genes (DEGs) were identified and the enrichment analysis detected starch and sucrose metabolism as a critical pathway in corm development, especially at the rapid swelling stage. Further, DEGs encoding key carbohydrate-metabolizing enzymes were identified and correlated to enzyme activities and carbohydrate accumulation. The results construct a valuable resource pool for further molecular-level studies, which are helpful for metabolic regulation of carbohydrates and improvement in F. hybrida.

Inhibition of a-amylase and a-glucosidase activities in vitro by extracts of selected medicinal plants

Abstract. Pant DR, Aryal B, Pun D, Sharma S, Joshi GP. 2021. Inhibition of a-amylase and a-glucosidase activities in vitro by extracts of selected medicinal plants. Biodiversitas 22: 1187-1193. Several medicinal plants are being used traditionally in the treatment/management of Diabetes Mellitus (DM). The present work focuses on experimental verification of antidiabetic potential of different medicinal plants that have been reported to be used traditionally to manage DM. Aqueous and methanolic extracts of 12 species of plants were studied for their inhibitory effect on the activities of a-amylase and a-glucosidase, two key enzymes of carbohydrate metabolism. The extracts of all the species showed very high degree (nearly 90% or above) of inhibition of α-amylase irrespective of the extraction solvent. The aqueous extracts of Asterella wallichiana, however, showed only 63.60% inhibition of a-amylase. Except for Asterella wallichiana, the percentage inhibition of a-amylase in aqueous and methanolic solution in all the species tested were almost similar. The percentage inhibition of a-glucosidase was lower than that of a-amylase for all the species in both types of extraction medium. The highest percentage inhibition of a-glucosidase (81.13±1.36 %) was found in methanolic extracts of Rhuschinensis. The inhibition of a-glucosidase was much higher in methanolic extracts than in aqueous extracts for all the species tested. High degree of inhibition of a-amylase activity in vitro by the extracts of all the species tested provides scientific basis for using these plants in the management/treatment of diabetes in traditional medicine.

Early-stage sugar beet taproot development is characterized by three distinct physiological phases.

Despite the agronomic importance of sugar beet (Beta vulgaris L.), the early‐stage development of its taproot has only been poorly investigated. Thus, the mechanisms that determine growth and sugar accumulation in sugar beet are largely unknown. In the presented study, a physiological characterization of early‐stage sugar beet taproot development was conducted. Activities were analyzed for fourteen key enzymes of carbohydrate metabolism in developing taproots over the first 80 days after sowing. In addition, we performed in situ localizations of selected carbohydrate‐metabolic enzyme activities, anatomical investigations, and quantifications of soluble carbohydrates, hexose phosphates, and phytohormones. Based on the accumulation dynamics of biomass and sucrose, as well as on anatomical parameters, the early phase of taproot development could be subdivided into three stages—prestorage, transition, secondary growth and sucrose accumulation stage—each of which was characterized by distinct metabolic and phytohormonal signatures. The enzyme activity signatures corresponding to these stages were also shown to be robustly reproducible in experiments conducted in two additional locations. The results from this physiological phenotyping approach contribute to the identification of the key regulators of sugar beet taproot development and open up new perspectives for sugar beet crop improvement concerning both physiological marker‐based breeding and biotechnological approaches.

Rumex dentatus L. phenolics ameliorate hyperglycemia by modulating hepatic key enzymes of carbohydrate metabolism, oxidative stress and PPARγ in diabetic rats

Rumex dentatus L. is a flowering plant with promising therapeutic effects. This study investigated the antioxidant efficacy of phenolic compounds isolated from R. dentatus L. in vitro and by conducting density function theory (DFT) studies to explore the mechanisms of action. The antioxidant, anti-inflammatory and antidiabetic effects of polyphenols-rich R. dentatus extract (RDE) were investigated in type 2 diabetic rats. Phytochemical investigation of the aerial parts of R. dentatus resulted in the isolation of one new and seven known compounds isolated for the first time from this species. All isolated phenolics showed in vitro radical scavenging activity. The antioxidant activity of the compounds could be oriented by the hydrogen atom transfer and sequential proton loss electron transfer mechanisms in gas and water phases, respectively. In diabetic rats, RDE attenuated hyperglycemia, insulin resistance and liver injury and improved carbohydrate metabolism. RDE suppressed oxidative stress and inflammation and upregulated PPARγ. In silico molecular docking analysis revealed the binding affinity of the isolated compounds toward PPARγ. In conclusion, the computational calculations were correlated with the in vitro antioxidant activity of R. dentatus derived phenolics. R. dentatus attenuated hyperglycemia, liver injury, inflammation and oxidative stress, improved carbohydrate metabolism and upregulated PPARγ in diabetic rats.

Antioxidant potential of biflavonoid attenuates hyperglycemia by modulating the carbohydrate metabolic enzymes in high fat diet/streptozotocin induced diabetic rats

ABSTRACT Objectives: The present study was to isolate the biflavonoid (a bimolecular kaemferol structured molecule) and test its efficacy on oxidative stress and carbohydrate metabolic key enzymes in control and high fat diet and streptozotocin -induced diabetic rats. Methods: Type 2 diabetes was induced in male albino wistar rats by feeding them with high fat diet comprising of 84.3% standard laboratory chow, 5% lard, 10% yolk powder, cholesterol 0.2%, and 0.5% bile salt for 2 weeks. After 2 weeks, the animals were kept in an overnight fast and injected with low dose of streptozotocin (35 mg/kg, dissolved in 0.1 M sodium citrate buffer, pH 4.5). Results: At the end of the experimental period, diabetic control rats showed significant increase in plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c) with concomitant decrease in plasma insulin, total hemoglobin and body weight. The activities of key enzymes of carbohydrate metabolism, lipid peroxidation markers, antioxidant enzymes, glycogen content and glycogen synthase and glycogen phosphorylase were also altered in diabetic rats. Discussion: Oral administration of biflavonoid to diabetic rats significantly ameliorated all the biochemical alterations to near normal levels. The effect produced by the biflavonoid on various parameters was comparable to that of metformin.

Bacoside-A diminishes liver functional enzymes and improves carbohydrate metabolic key enzymes in streptozotocin a rat model of T2DM

Abstract Type 2 diabetes mellitus (T2DM) is a global alarming predominant metabolic disease than other diabetes and incurs substantial burden to public and healthcare systems. Our study is designed to endeavor the valuable effect of bacoside-A on hepatic key enzymes of carbohydrate metabolism in streptozotocin (STZ) induced diabetic rats. A single intraperitoneal (i.p) injection of STZ (40 mg/kg body weight [BW]) is administered to adult male Wistar rats for the attainment of diabetes. Diabetic rats were orally treated with bacoside-A of various doses (5, 10 and 20 mg/kg BW) for 45 days. Bacoside-A (10 mg/kg BW) showed more pronounced effect than the other doses and thus resulted in a significant reduction in the level of plasma glucose, glycosylated hemoglobin (HbA1c) and an rise in insulin and hemoglobin levels. Administration of bacoside-A showed significant elevated in the activity of glycolytic enzyme (hexokinase) and hepatic shunt enzyme (glucose-6-phophate dehydrogenase) whereas significant decline in the activity of gluconeogenic enzymes (glucose-6-phosphatase and fructose-1,6-bisphosphatase) in diabetic rats. Further, bacoside-A administration to diabetic rats enhanced body weight, liver glycogen content and modulating its metabolizing enzymes (glycogen synthase and glycogen phosphorylase) demonstrated the antihyperglycemic potential of bacoside-A in diabetic rats. Furthermore, hepatic marker enzymes such as aspartate transaminases (AST) and alanine transaminases (ALT) activities significantly decreased in diabetic rats and tend to normalcy in bacoside-A treated diabetic rats. Glibenclamide, a reference drug. In conclusion, our data explicated the bacoside-A, a promising antidiabetic agent which infers in modulating hepatic key enzymes by preventing defect in carbohydrate metabolism against T2DM.

Hesperidin, a citrus flavonoid ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats

The present study investigated the protective effect of hesperidin on carbohydrate metabolizing enzymes in streptozotocin-induced diabetic rats. Hesperidin was administered to streptozotocin-induced (40 mg/kg b.w.) diabetic rats at different dosages of (25, 50, 100 mg/kg b.w.) respectively for 30 days to evaluate its effect on fasting plasma glucose, insulin, glycosylated hemoglobin, hemoglobin, and carbohydrate metabolic enzymes. The plasma glucose levels were significantly reduced in a dose-dependent manner in hesperdin-treated group of rats when compared to the diabetic control rats. In addition, concomitant increase in hemoglobin and insulin levels and a decrease in glycosylated hemoglobin were observed in treated group of rats. The activities of the hepatic key enzymes of carbohydrate metabolism such as hexokinase and glucose-6-phosphate dehydrogenase were significantly increased, whereas glucose-6-phosphatase and fructose-1,6-bisphosphatase were significantly decreased. Furthermore, hesperidin administration prevented the loss in body weight and improved the glycogen content in the hepatic tissue of diabetic animals by reinstating the activities of glycogen synthase and glycogen phosphorylase. These results showed that hesperidin has potential antihyperglycemic activity in streptozotocin-induced diabetic rats. This was further supported by the histological studies of pancreas and liver.

Antioxidant potential of theaflavin ameliorates the activities of key enzymes of glucose metabolism in high fat diet and streptozotocin – induced diabetic rats

ABSTRACTObjectives: The present study was to evaluate the effect of theaflavin on the activities of key enzymes of carbohydrate metabolism in high fat diet and streptozotocin – induced diabetic rats.Methods: Diabetes was induced in male albino Wistar rats by feeding them with high fat diet comprising of standard laboratory rat chow 84.3%, lard 5%, egg yolk powder 10%, cholesterol 0.2% and bile salt 0.5% for 2 weeks. After 2 weeks, the animals were kept in an overnight fast and injected with low dose of streptozotocin (40 mg/kg b.w).Results: Theaflavin (100 mg/kg b.w /day) was administered orally to diabetic rats for 30 days. At the end of the experimental period, diabetic control rats showed significant increase in plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c) with concomitant decrease in plasma insulin, total hemoglobin and body weight. The activities of key enzymes of carbohydrate metabolism, lipid peroxidation markers, antioxidant enzymes, glycogen content and glycogen synthase and glycogen phosphorylase were also altered in diabetic rats.Discussion: Oral administration of theaflavin to diabetic rats significantly ameliorated all the biochemical alterations to near normal levels. The results of the present study suggest that theaflavin exhibits antidiabetic effect through its antioxidant activity.

Challenges during diapause and anhydrobiosis: Mitochondrial bioenergetics and desiccation tolerance.

In preparation for the onset of environmental challenges like overwintering, food limitation, anoxia, or water stress, many invertebrates and certain killifish enter diapause. Diapause is a developmentally-programed dormancy characterized by suppression of development and metabolism. For embryos of Artemia franciscana (brine shrimp), the metabolic arrest is profound. These gastrula-stage embryos depress oxidative metabolism by ~99% during diapause and survive years of severe desiccation in a state termed anhydrobiosis. Trehalose is the sole fuel source for this developmental stage. Mitochondrial function during diapause is downregulated primarily by restricting substrate supply, as a result of inhibiting key enzymes of carbohydrate metabolism. Because proton conductance across the inner membrane is not decreased during diapause, the inference is that membrane potential must be compromised. In the absence of any intervention, the possibility exists that the F1 Fo ATP synthase and the adenine nucleotide translocator may reverse, leading to wholesale hydrolysis of cellular ATP. Studies with anhydrobiotes like A. franciscana are revealing multiple traits useful for improving desiccation tolerance that include the expression and accumulation late embryogenesis abundant (LEA) proteins and trehalose. LEA proteins are intrinsically disordered in aqueous solution but gain secondary structure (predominantly α-helix) as water is removed. These protective agents stabilize biological structures including lipid bilayers and mitochondria during severe water stress. © 2018 IUBMB Life, 70(12):1251-1259, 2018.

LncRNA Ftx promotes aerobic glycolysis and tumor progression through the PPARγ pathway in hepatocellular carcinoma.

Aerobic glycolysis is a phenomenon by which malignant cells preferentially metabolize glucose through the glycolytic pathway, rather than oxidative phosphorylation to proliferate efficiently. The present study aimed to investigate the expression and functional implications of long non-coding (lnc)RNA Ftx in the aerobic glycolysis and tumorigenesis of hepatocellular carcinoma (HCC). It was identified that lncRNA Ftx was upregulated in human HCC tissues and cell lines and, notably, was associated with aggressive clinicopathological features. lncRNA Ftx overexpression promoted the proliferation, invasion and migration of HCC cells, whereas lncRNA Ftx knockdown resulted in the opposite effects. Furthermore, lncRNA Ftx affected the activity and expression of key enzymes in carbohydrate metabolism, suggesting that lncRNA Ftx may be involved in aerobic glycolysis in HCC. The measurement of glucose consumption, lactate production and glucose transporter expression further supported this assumption. Mechanistically, peroxisome proliferator-activated receptor γ (PPARγ) expression in human HCC tissues and cell lines was positively correlated with lncRNA Ftx. Inhibiting PPARγ in Huh7 cells partially abrogated the alterations in glucose uptake, lactate production and relative glycolytic enzyme expression induced by lncRNA Ftx; similarly, PPARγ activation in Bel-7402 cells partially rescued the lncRNA Ftx-mediated alterations. In conclusion, lncRNA Ftx is a promoter of the Warburg effect and tumor progression, partly via the PPARγ pathway, and may serve as a promising therapeutic target for HCC treatment.