G6Pase Gene Research Articles

A High-Fat and High-Fructose Diet Exacerbates Liver Dysfunction by Regulating Sirtuins in a Murine Model.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as the most prevalent chronic liver disease, closely linked to the escalating rates of diabesity. The Western diet's abundance of fat and fructose significantly contributes to MASLD, disrupting hepatic glucose metabolism. We previously demonstrated that a high-fat and high-fructose diet (HFHFD) led to increased body and liver weight compared to the low-fat diet (LFD) group, accompanied by glucose intolerance and liver abnormalities, indicating an intermediate state between fatty liver and liver fibrosis in the HFHFD group. Sirtuins are crucial epigenetic regulators associated with energy homeostasis and play a pivotal role in these hepatic dysregulations. Our investigation revealed that HFHFD significantly decreased Sirt1 and Sirt7 gene and protein expression levels, while other sirtuins remained unchanged. Additionally, glucose 6-phosphatase (G6Pase) gene expression was reduced in the HFHFD group, suggesting a potential pathway contributing to fibrosis progression. Chromatin immunoprecipitation analysis demonstrated a significant increase in histone H3 lysine 18 acetylation within the G6Pase promoter in HFHFD livers, potentially inhibiting G6Pase transcription. In summary, HFHFD may inhibit liver gluconeogenesis, potentially promoting liver fibrosis by regulating Sirt7 expression. This study offers an epigenetic perspective on the detrimental impact of fructose on MASLD progression.

Impact of hypoxia on glucose metabolism and hypoxia signaling pathways in juvenile horseshoe crabs Tachypleus tridentatus

Marine hypoxia poses a significant challenge in the contemporary marine environment. The horseshoe crab, an ancient benthic marine organism, is confronted with the potential threat of species extinction due to hypoxia, making it an ideal candidate for studying hypoxia tolerance mechanisms. In this experiment, juvenile Tachypleus tridentatus were subjected to a 21-day trial at DO:2 mg/L (hypoxia) and DO:6 mg/L conditions. The experimental timeline included a 14-day exposure phase followed by a 7-day recovery period. Sampling occurred on days 0, 7, 14, and 21, where the period from day 14 to day 21 corresponds to seven days of recuperation. Several enzymatic activities of important proteins throughout this investigation were evaluated, such as succinate dehydrogenase (SDH), phosphofructokinase (PFK), hexokinase (HK), lactate dehydrogenase (LDH), and pyruvate kinase (PK). Concurrently, the relative expression of hexokinase-1 (HK), hypoxia-inducible factor 1-alpha inhibitor (FIH), and hypoxia-inducible factor 1-alpha (HIF-1α), pyruvate dehydrogenase phosphatase (PDH), succinate dehydrogenase assembly factor 4 (SDH), and Glucose-6-phosphatase (G6Pase) were also investigated. These analyses aimed to elucidate alterations in the hypoxia signaling pathway and respiratory energy metabolism. It is revealed that juvenile T. tridentatus initiated the HIF pathway under hypoxic conditions, resulting in an upregulation of HIF-1α and FIH-1 gene expression, which in turn, influenced a shift in metabolic patterns. Particularly, the activity of glycolysis-related enzymes was promoted significantly, including PK, HK, PKF, LDH, and the related HK gene. In contrast, enzymes linked to aerobic respiration, PDH, and SDH, as well as the related PDH and SDH genes, displayed down-regulation, signifying a transition from aerobic to anaerobic metabolism. Additionally, the activity of gluconeogenesis-related enzymes such as PK and G6Pase gene expression were significantly elevated, indicating the activation of gluconeogenesis and glycogenolysis pathways. Consequently, juvenile T. tridentatus demonstrated an adaptive response to hypoxic conditions, marked by changes in respiratory energy metabolism modes and the activation of hypoxia signaling pathways.

Preparation and identification of hypoglycemic bioactive peptide from Amygdalus communis L. by multienzyme hydrolysis

Amygdalus communis L. is rich in high-quality protein and its natural peptides have potential in controlling and preventing diseases. The objective of this study was to evaluate the hypoglycemic activity of bioactive peptides obtained from Amygdalus communis L. protein by synergistic hydrolysis of trypsin and protamex. After ultrafiltration and purification, active peptide B4 with small molecular weight in four hypoglycemic active peptides showed the best inhibitory activities on α-amylase and α-glucosidase. Moreover, insulin resistance model was established with HepG2 cells to study the hypoglycemic mechanism of active peptide B4. The experimental results confirmed that the active peptide B4 was able to up-regulate GYS1 gene mRNA expression and down-regulate PEPCK, G6Pase and GP gene mRNA expression. Meanwhile, active peptide B4 significantly increased the glucose consumption and glycogen synthesis in IR-HepG2. This research enhances the additional value of nut proteins and contributes to the development of potential functional products to expand their application in the food field.

Mild Intermittent Cold Stimulation Affects Cardiac Substance Metabolism via the Neuroendocrine Pathway in Broilers.

This study aimed to investigate the impact of cold adaptation on the neuroendocrine and cardiac substance metabolism pathways in broilers. The broilers were divided into the control group (CC), cold adaptation group (C3), and cold-stressed group (C9), and experimental period was divided into the training period (d 1-35), recovery period (d 36-43), and cold stress period (d 43-44). During the training period, the CC group was reared at ambient temperature, while C3 and C9 groups were reared at 3 °C and 9 °C lower than the ambient temperature, respectively, for 5 h/d at 1 d intervals. During the recovery period, all the groups were maintained at 20 °C. Lastly, during the cold stress period, the groups were divided into two sub-groups, and each sub-group was placed at 10 °C for 12 h (Y12) or 24 h (Y24) for acute cold stimulation. The blood, hypothalamic, and cardiac tissues samples were obtained from all the groups during the training, recovery, and acute stress periods. The results revealed that the transcription of calcium voltage-gated channel subunit alpha 1 C (CACNAIC) was increased in the hypothalamic tissues of the C3 group (p < 0.05). Moreover, compared to the CC group, the serum norepinephrine (NE) was increased in the C9 group (p < 0.05), but insulin (INS) was decreased in the C9 group (p < 0.05). In addition, the transcription of the phosphoinositide-3 kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), SREBP1c, FASN, ACC1, and SCD genes was down-regulated in the C3 and C9 groups (p < 0.05); however, their expression increased in the C3 and C9 groups after acute cold stimulation (p < 0.05). Compared to the CC group, the transcription of forkhead box O1 (FoxO1), PEPCK, G6Pase, GLUT1, HK1, PFK, and LDHB genes was up-regulated in the C3 and C9 groups (p < 0.05. Furthermore, compared to the CC and C9 groups, the protein and mRNA expressions of heat shock protein (HSP) 70 and HSP90 were significantly increased in the C3 group (p < 0.05). These results indicate that intermittent cold training can enhance cold stress tolerance in broilers by regulating their neuroendocrine and cardiac substance metabolism pathways.

Hypoglycemic Effect of Trichosanthes pericarpium to Type 2 Model Diabetic Mice via Intestinal Bacteria Transplantation.

The treatment of diabetes with plant ingredients such as in Traditional Chinese Medicine (TCM) is an alternative to classical chemotherapy. This study aims to explore the hypoglycemic effect of Trichosanthes pericarpium powder (TP) and intestinal bacteria transplantation in type 2 diabetic mice. The relationship between intestinal bacteria transplantation and improvement in insulin resistance was also investigated. The polyphenols and terpenoids in the TP were identified by LC-MS/MS. Streptozotocin was used to induce a mouse model of type 2 diabetes. Diabetic mice were treated with different doses of TP and the intestinal bacteria obtained from the high-dose TP group for four weeks. As a result, FBG levels were found to be significantly reduced in diabetic mice, weight gain and organ enlargement were alleviated, and insulin resistance was significantly improved. TP administration also improved the disorder in intestinal bacteria in diabetic mice. Besides, TP can increase the liver AMPK, SIRT1, GLUT1, and GLUT4 gene expression, while down-regulated PEPCK and G6Pase gene expression suggest a potential mechanism for hypoglycemia in diabetic mice. Oral administration of Trichosanthes pericarpium powder in the treatment of diabetes may be achieved by restoring hepatic function, improving insulin resistance, and the dynamic balance of intestinal bacteria.

Impact of Oral Administration of Lactiplantibacillus plantarum Strain CNCM I-4459 on Obesity Induced by High-Fat Diet in Mice.

Recent evidence suggests that some lactobacilli strains, particularly Lactiplantibacillus plantarum, have a beneficial effect on obesity-associated syndromes. Several studies have investigated probiotic challenges in models of high-fat diet (HFD)-induced obesity, specifically with respect to its impact on hepatic and/or adipocyte metabolism, gut inflammation and epithelial barrier integrity, and microbiota composition. However, only a few studies have combined these aspects to generate a global understanding of how probiotics exert their protective effects. Here, we used the probiotic strain L. plantarum CNCM I-4459 and explored its impact on a mouse model of HFD-induced obesity. Briefly, mice were administered 1 × 109 CFUs/day and fed HFD for 12 weeks. Treatment with this strain improved insulin sensitivity by lowering serum levels of fasting glucose and fructosamine. Administration of the probiotic also affected the transport and metabolism of glucose, resulting in the downregulation of the hepatic Glut-4 and G6pase genes. Additionally, L. plantarum CNCM I-4459 promoted a decreased concentration of LDL-c and modulated hepatic lipid metabolism (downregulation of Fasn, Plin, and Cpt1α genes). Probiotic treatment also restored HFD-disrupted intestinal microbial composition by increasing microbial diversity and lowering the ratio of Firmicutes to Bacteroidetes. In conclusion, this probiotic strain represents a potential approach for at least partial restoration of the glucose sensitivity and lipid disruption that is associated with obesity.

Shrimp Glucose-6-phosphatase 2 (G6Pase 2): a second isoform of G6Pase in the Pacific white shrimp and regulation of G6Pase 1 and 2 isoforms via HIF-1 during hypoxia and reoxygenation in juveniles.

Animals suffer hypoxia when their oxygen consumption is larger than the oxygen available. Hypoxia affects the white shrimp Penaeus (Litopenaeus) vannamei, both in their natural habitat and in cultivation farms. Shrimp regulates some enzymes that participate in energy production pathways as a strategy to survive during hypoxia. Glucose-6-phosphatase (G6Pase) is key to maintain blood glucose homeostasis through gluconeogenesis and glycogenolysis. We previously reported a shrimp G6Pase gene (G6Pase1) and in this work, we report a second isoform that we named G6Pase2. The expression of the two isoforms was evaluated in oxygen limited conditions and during silencing of the transcription factor HIF-1. High G6Pase activity was detected in hepatopancreas followed by muscle and gills under good oxygen and feeding conditions. Gene expression of both isoforms was analyzed in normoxia, hypoxia and reoxygenation in hepatopancreas and gills, and in HIF-1-silenced shrimp. In fed shrimp with normal dissolved oxygen (DO) (5.0mg L- 1 DO) the expression of G6Pase1 was detected in gills, but not in hepatopancreas or muscle, while G6Pase2 expression was undetectable in all three tissues. In hepatopancreas, G6Pase1 is induced at 3 and 48h of hypoxia, while G6Pase2 is down-regulated in the same time points but in reoxygenation, both due to the knock-down of HIF-1. In gills, only G6Pase1 was detected, and was induced by the silencing of HIF-1 only after 3h of reoxygenation. Therefore, the expression of the two isoforms appears to be regulated by HIF-1 at transcriptional level in response to oxygen deprivation and subsequent recovery of oxygen levels.

FAM3D inhibits gluconeogenesis in high glucose environment via DUSP1/ZFP36/SIK1 axis.

Hyperglycemia is the most important factor leading to the complications of type 2 diabetes mellitus (T2DM). The primary condition for the treatment of T2DM is to change the glucose and lipid metabolism disorders in the liver and other insulin-sensitive tissues. The current study aims to unearth the potential molecular mechanism of inhibiting liver gluconeogenesis to provide a new theoretical basis for the treatment of T2DM. High glucose (HG) induction of HepG2 cells followed by treatment with sequence-similar family 3 member D (FAM3D). Dual specificity phosphatases 1 (DUSP1), zinc finger protein 36 (ZFP36), salt-induced kinase 1 (SIK1), p-SIK1, posphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene and protein expression level were detected by quantitative real-time polymerase chain reaction and western blot. The PEPCK and G6Pase activities were detected by enzyme linked immunosorbent assay. Glucose production assay to determine glucose content. The RNA binding protein immunoprecipitation assay was used to detect the binding of ZFP36 to SIK1. FAM3D facilitated the expression of DUSP1 but suppressed the expression of gluconeogenesis-related factors in an HG environment. The expression of ZFP36 was up-regulated in an HG environment. ZFP36 could reverse the inhibition of gluconeogenesis caused by FAM3D. HG-induced upregulation of ZFP36 was downregulated by overexpression of DUSP1. ZFP36 bound to SIK1, and downregulation of ZFP36 promoted SIK1 expression and inhibits gluconeogenesis. Our study demonstrated FAM3D inhibited gluconeogenesis through the DUSP1/ZFP36/SIK1 axis in an HG environment, which provided a new theoretical basis for exploring the pathogenesis and treatment strategy of T2DM.

Vulgarin, a Sesquiterpene Lactone from Artemisia judaica, Improves the Antidiabetic Effectiveness of Glibenclamide in Streptozotocin-Induced Diabetic Rats via Modulation of PEPCK and G6Pase Genes Expression.

The current investigation assessed the effect of the eudesmanolid, Vulgarin (VGN), obtained from Artemisia judaica (A. judaica), on the antidiabetic potential of glibenclamide (GLB) using streptozotocin (STZ) to induce diabetes. Seven groups of rats were used in the study; the first group received the vehicle and served as normal control. The diabetic rats of the second to the fifth groups were treated with the vehicle (negative control), GLB at 5 mg/kg (positive control), VGN at 10 mg/kg (VGN-10) and VGN at 20 mg/kg (VGN-20), respectively. The diabetic rats of the sixth and seventh groups were administered combinations of GLB plus VGN-10 and GLB plus VGN-20, respectively. The diabetic rats treated with GLB plus VGN-20 combination showed marked improvement in the fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c), as well as the lipid profile, compared with those treated with GLB alone. Further, the pancreatic tissues of the diabetic rats that received the GLB+VGN-20 combination showed superior improvements in lipid peroxidation and antioxidant parameters than those of GLB monotherapy. The insulin content of the β-cells was restored in all treatments, while the levels of glucagon and somatostatin of the α- and δ-endocrine cells were reduced in the pancreatic islets. In addition, the concurrent administration of GLB+VGN-20 was the most effective in restoring PEPCK and G6Pase mRNA expression in the liver. In conclusion, the results demonstrated that the GLB+VGN-20 combination led to greater glycemic improvement in diabetic rats compared with GLB monotherapy through its antioxidant effect and capability to modulate PEPCK and G6Pase gene expression in their livers.

Glycogen storage disease type Ia misdiagnosed as multiple acyl-coenzyme A dehydrogenase deficiency by mass spectrometry.

To report a case of glycogen storage disease (GSD) type Ia misdiagnosed as multiple acyl-coenzyme a dehydrogenase deficiency (MADD) by mass spectrometry. A 7 months old boy was admitted to our hospital for elevated transaminase levels lasting more than 1 month. His blood biochemistry showed hypoglycemia, metabolic acidosis, hyperlipidemia, elevated lactate and uric acid, elevated alanine amino transferase (ALT), aspartate amino transaminase (AST) and gamma-glutamyl transferase (GGT). Mass spectrometry analysis of blood and urine showed elevated blood acylcarnitines and dicarboxylic aciduria, indicating multiple acyl-coenzyme A dehydrogenase deficiency. Sanger sequencing of all exons of glucose-6-phosphatase (G6Pase) and electronic transfer flavoprotein dehydrogenase (ETFDH) was performed for the patient and his parents. Coding and flanking sequences of the G6Pase gene detected two heterozygous single base substitutions in the boy. One variant was in exon 1 (c.209G > A), Which was also detected in the father. Another was in exon 5 (c.648G > T), which was detected in the mother. Coding and flanking sequences of the ETFDH gene revealed no pathogenic/likely pathogenic variants in the boy. GSD Ia can manifest elevated blood acyl carnitines and dicarboxylic aciduria which were the typical clinical manifestations of MADD. So the patient with clinical manifestations similar to MADD is in need of differential diagnosis for GSD Ia. Genetic testing is helpful to confirming the diagnosis of inherited metabolic diseases.

HM-chromanone suppresses hepatic glucose production via activation of AMP-activated protein kinase in HepG2 cell

We investigated whether (E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone (HM-chromanone) could suppress the transcription factors expression and enzymes involved in glucose production by activating AMPK in hepatocytes. HepG2 cells were treated with a medium containing HM-chromanone (5–100 μM), compound C (10 μM) and insulin (100 nM). Glucose production and glycogen synthesis assay were determined using a glucose assay kit and glycogen assay kit, respectively. Activities of AMP-activated protein kinase (AMPK), acetyl CoA carboxylase (ACC), cAMP response element-binding protein (CREB), PPAR coactivator-1α (PGC1α), CREB-regulated transcription coactivator 2 (CRTC2), Glycogen synthase kinase (GSK3β), Phosphoenolpyruvate carboxykinase (PEPCK), glycogen synthase (GS), Glucose 6-phosphatase (G6pase) and β-actin were determined by Western blot analysis. HM-chromanone significantly inhibited hepatic glucose production and increased glycogen synthesis by activating glycogen synthase. HM-chromanone induced the phosphorylation of CRTC2 and GSK-3β by phosphorylating AMPK in HepG2 cells, which was confirmed by compound C. Furthermore, it significantly decreased the phosphorylation of CREB in a time- and concentration-dependent manner, and the effect was reversed in the presence of compound C. Therefore, the complex formation of CRTC2 and CREB was inhibited. HM-chromanone inhibited the expression of PGC-1α, PEPCK, and G6Pase genes involved in production of hepatic glucose. The results showed that HM-chromanone activates AMPK in a time and concentration dependent manner, thus suppressing hepatic glucose production and increasing glycogen synthesis in HepG2 cells.

Anti-hyperglycemic effects of Eryngium billardierei F. Delaroche extract on insulin-resistance HepG2 cells in vitro

Insulin resistance as a major problem is associated with type 2 diabetes mellitus. This study investigated the effect of Eryngium billardierei on insulin-resistance induced HepG2 cells. MTT method was used to evaluate the viability of HepG2 cells treated with various doses of E. billardierei extract. An insulin-resistance model was established in HepG2 cells. Next, MTT assay and Acridine orange staining were performed to investigate the viability of cells in the vicinity of different concentrations of insulin, pioglitazone, and E. billardierei extract in an insulin-resistance media. The glucose uptake test was performed to select the optimal insulin concentration. Expression levels of IR, G6Pase, and PEPCK genes were assessed by real-time RT-PCR. According to obtained data, E. billardierei at concentrations of 0.5 and 1mg/mL show no toxicity on cells. Furthermore, based on MTT assay and glucose uptake test 10-5mol/L insulin was chosen as the model group to induce insulin-resistance in HepG2 cells for gene expression analysis. Finally, 1mg/mL E. billardierei not only induced no cytotoxicity but also showed an increase in the expression of IR as well as a reduction in G6Pase and PEPCK level compared to the control and model groups. The obtained data indicated that 1mg/mL E. billardierei might have an anti-insulin resistance effect on insulin-resistance HepG2 cells in vitro and could be a promising candidate with anti-hyperglycemic properties for diabetes treatments.

A New lncRNA, lnc-LLMA, Regulates Lipid Metabolism in Pig Hepatocytes.

A large variety of long noncoding RNAs (lncRNAs) have been discovered through high-throughput sequencing technology and some have been demonstrated to play important roles in lipid metabolism regulation. In our study, we found a highly expressed lncRNA (lnc-LLMA, liver lipid metabolism-associated lncRNA) in the liver of Duroc pigs, which was enriched in the nucleus. It displays potent tissue specificity among different pig breeds. Overexpression of lnc-LLMA can cause a decline in intracellular triglyceride (TG) levels and increases in ATP and mitochondrial DNA levels in pig primary hepatocytes and HepG2 cells. In addition, the expression levels of MTTP, APOB, CPT1α, and other genes were increased by overexpression of lnc-LLMA. It downregulated expression of G6Pase and SREBP1 genes. Chromatin isolation by RNA purification (ChRIP) experiments demonstrated that microsomal triglyceride transfer protein (MTTP) and glycogen synthase 2 (GYS2) were the potential interacting proteins of lnc-LLMA. The overexpression of the GYS2 gene rescued the decreasing intracellular TG levels caused by the increase of lnc-LLMA. Similarly, overexpression of MTTP was also able to save the lnc-LLMA-induced decrease in intracellular TG. Our study demonstrated that this novel lncRNA was closely related to lipid metabolism and affected lipid transport and mitochondrial function through MTTP and GYS2. Our results provided a new direction for further studying the effect of lncRNA on lipid metabolism regulation.

Spirulina liquid extract prevents metabolic disturbances and improves liver sphingolipids profile in hamster fed a high-fat diet.

Metabolic syndrome is characterized by hyperglycemia, hyperlipemia and exacerbated oxidative stress. The aim of the study was to determine whether Spirulysat®, a Spirulina liquid extract (SLE) enriched in phycocyanin, would prevent metabolic abnormalities induced by high-fat diet. The effect of acute SLE supplementation on postprandial lipemia and on triton-induced hyperlipidemia was studied in hamster fed control diet (C). The effect of chronic SLE supplementation on lipid content in plasma, liver and aorta, and on glycemia and oxidative stress was studied in hamster fed control (C) or high-fat diet (HF) for two weeks and then treated with SLE for two weeks (CSp and HFSp) or not (C and HF). The acute SLE supplementation lowered plasma cholesterol and non-esterified fatty acid concentrations after olive oil gavage (P < 0.05) in CSp, while no effect was observed on triglyceridemia. HFD increased plasma MDA, basal glycemia, triglyceridemia, total plasma cholesterol, VLDL, LDL and HDL cholesterol, ceramide, sphingomyelin and glucosylceramide content in liver in HF compared to C (P < 0.05). SLE did not affect SOD and GPx activities nor total antioxidant status in HFSp group but lowered glycemia, glucoceramide and cholesterol in liver and cholesterol in aorta compared to HF (P < 0.05). SLE also decreased HMGCoA and TGF-β1 gene expression in liver (P < 0.05) and tended to lower G6Pase (P = 0.068) gene expression in HFSp compared to HF. Although 2-week SLE supplementation did not affect oxidative stress, it protected from hyperglycemia and lipid accumulation in liver and aorta suggesting a protective effect against metabolic syndrome.

Tiliacora triandra (Colebr.) Diels Leaf Aqueous Extract Inhibits Hepatic Glucose Production in HepG2 Cells and Type 2 Diabetic Rats.

This study investigated the effects of Tiliacora triandra (Colebr.) Diels aqueous extract (TTE) on hepatic glucose production in hepatocellular carcinoma (HepG2) cells and type 2 diabetic (T2DM) conditions. HepG2 cells were pretreated with TTE and its major constituents found in TTE, epicatechin (EC) and quercetin (QC). The hepatic glucose production was determined. The in vitro data were confirmed in T2DM rats, which were supplemented daily with 1000 mg/kg body weight (BW) TTE, 30 mg/kg BW metformin or TTE combined with metformin for 12 weeks. Results demonstrate that TTE induced copper-zinc superoxide dismutase, glutathione peroxidase and catalase genes, similarly to EC and QC. TTE decreased hepatic glucose production by downregulating phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and increasing protein kinase B and AMP-activated protein kinase phosphorylation in HepG2 cells. These results correlated with the antihyperglycemic, antitriglyceridemic, anti-insulin resistance, and antioxidant activities of TTE in T2DM rats, similar to the metformin and combination treatments. Consistently, impairment of hepatic gluconeogenesis in T2DM rats was restored after single and combined treatments by reducing PEPCK and G6Pase genes. Collectively, TTE could potentially be developed as a nutraceutical product to prevent glucose overproduction in patients with obesity, insulin resistance, and diabetes who are being treated with antidiabetic drugs.

The Effect of Resistance Training on G6Pase Gene Expression in Liver Hepatocytes, Glucose and Insulin Resistance Levels in Type 2 Diabetic Rats

Objective: The aim of this study was to determine the effect of 12 weeks resistance training on G6Pase expression in liver cells, as well as glucose and insulin levels in type 2 diabetic rats. Materials and Methods: In this experimental study, 16 wistar rats were selected as the research sample. After injection of nicotinamide and streptozocin to induce diabetes, the rats were randomly divided into two groups of resistance training and control. The resistance group participated in a course of resistance training for up to 12 week in five sessions per week, with intensity of 75% and a time of 30 to 45 minutes. Finally, 48 hours after the last exercise session, G6Pase expression in liver cells, as well as glucose and insulin levels were measured in both groups. Results: Comparison of resistance and control training groups showed a decrease in glucose levels (P-value= 0.001) and increased insulin levels (P-value= 0.001). Exercise also reduced the expression of G6Pase in liver cells in the resistance training group (P-value= 0.001). Conclusion: Based on the results of the study, it is recommended that diabetics use resistance training under the supervision of a specialist to reduce the negative effects of diabetes.

Glucose Utilization in the Regulation of Chitin Synthesis in Brown Planthopper.

Glucose-6-phosphatase (G6Pase) and hexokinase (HK) are two key enzymes in the glycolysis and gluconeogenesis pathways, which catalyze the synthesis and degradation of glucose in insects, respectively. G6Pase and HK play an important role in insect growth by regulating the metabolism of glucose, leading to the efficient metabolism of other macromolecules. However, it is unclear whether these genes could be investigated for pest control through their actions on chitin metabolism. We studied the potential functions of G6Pase and HK genes in the regulation of chitin metabolism pathways by RNAi technology. Interference with G6Pase expression did not affect trehalose and chitin metabolism pathways in brown planthopper, Nilaparvata lugens (Stål). However, knockdown of the HK gene resulted in a significant decrease of expression of genes associated with the trehalose metabolic pathway but had no significant effect on trehalase activity, trehalose content, or glucogen content. Additionally, HK knockdown resulting in downregulation of the genes involved in chitin metabolism in the brown planthopper. These insects also showed wing deformities and difficulty in molting to varying degrees. We suggest that the silencing of HK expression directly inhibited the decomposition of glucose, leading to impaired chitin synthesis.

Evaluation of anti-diabetic attributes of Lactobacillus rhamnosus MTCC: 5957, Lactobacillus rhamnosus MTCC: 5897 and Lactobacillus fermentum MTCC: 5898 in streptozotocin induced diabetic rats

Interest in probiotics has grown significantly in the last decades due to their reported nutritional and health promoting effects. The aim of this study is to investigate the therapeutic potential of probiotic fermented milk (PFM) prepared using three different probiotic strains i.e. Lactobacillus rhamnosus MTCC: 5957, Lactobacillus rhamnosus MTCC: 5897 and Lactobacillus fermentum MTCC: 5898; independently or in combination, for treating streptozotocin induced type-1 diabetes in male Wistar rats. Diabetic rats were fed with PFM preparations for 6 weeks and then analyzed for the various biochemical parameters associated. The results indicated that feeding of PFM significantly improved glucose metabolism (fasting blood glucose, glycated hemoglobin, serum insulin), serum inflammation status (tumor necrosis factor-α, and serum interleukin-6), oxidative stress (thiobarbituric acid reactive substance, catalase, superoxide dismutase and glutathione peroxidase activities in liver and kidney), serum lipid profile (total cholesterol, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, triglycerides) in diabetic rats. In addition, feeding of PFM has significantly reduced mRNA expression of pepck and g6pase genes that code the key enzymes of gluconeogenesis pathway. The results of this study showed that daily consumption of PFM can be effective in combating of type −1 diabetes and its complications.

The SMILE transcriptional corepressor inhibits cAMP response element–binding protein (CREB)–mediated transactivation of gluconeogenic genes

Under fasting conditions, activation of several hepatic genes sets the stage for gluconeogenesis in the liver. cAMP response element-binding protein (CREB), CREB-regulated transcription coactivator 2 (CRTC2), and peroxisome proliferator-activated receptor γ coactivator 1-alpha (PGC-1α) are essential for this transcriptional induction of gluconeogenic genes. PGC-1α induction is mediated by activation of a CREB/CRTC2 signaling complex, and recent findings have revealed that small heterodimer partner-interacting leucine zipper protein (SMILE), a member of the CREB/ATF family of basic region-leucine zipper (bZIP) transcription factors, is an insulin-inducible corepressor that decreases PGC-1α expression and abrogates its stimulatory effect on hepatic gluconeogenesis. However, the molecular mechanism whereby SMILE suppresses PGC-1α expression is unknown. Here, we investigated SMILE's effects on the CREB/CRTC2 signaling pathway and glucose metabolism. We found that SMILE significantly inhibits CREB/CRTC2-induced PGC-1α expression by interacting with and disrupting the CREB/CRTC2 complex. Consequently, SMILE decreased PGC-1α-induced hepatic gluconeogenic gene expression. Furthermore, SMILE inhibited CREB/CRTC2-induced phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene expression by directly repressing the expression of these genes and by indirectly inhibiting the expression of PGC-1α via CREB/CRTC2 repression. Indeed, enhanced gluconeogenesis and circulating blood glucose levels in mice injected with an adenovirus construct containing a constitutively active CRTC2 variant (CRTC2-S171A) were significantly reduced by WT SMILE, but not by leucine zipper-mutated SMILE. These results reveal that SMILE represses CREB/CRTC2-induced PGC-1α expression, an insight that may help inform potential therapeutic approaches targeting PGC-1α-mediated regulation of hepatic glucose metabolism.

AMPK activation by pterostilbene contributes to suppression of hepatic gluconeogenic gene expression and glucose production in H4IIE cells

Pterostilbene, a bioactive component of blueberries and grapes, shows structural similarity to resveratrol, and exhibits antioxidant, anti-inflammatory, anti-cancer, hypoglycemic, and cholesterol lowering effects. Recent evidence indicates that pterostilbene is an agonist of the nuclear receptor, peroxisome proliferator-activated receptor-alpha (PPAR-α). Since PPAR-α agonists induce peroxisomal proliferation and fatty acid oxidation, we examined gene expression of acyl CoA oxidase (ACO) and carnitine palmitoyl transferase-1 (CPT-1). Pterostilbene treatment, at concentrations that demonstrated over 75% cell viability (20 μM, 50 μM), significantly increased gene expression of ACO, CPT-1, and PPAR-α. Pterostilbene treatment (50 μM) also demonstrated potent activation of AMP-activated kinase (AMPK), compared to AICAR (0.5 mM) or metformin (2 mM), consistent with upregulation in fatty acid oxidation gene expression. Since AMPK activators mimic the actions of insulin by repressing hepatic gluconeogenesis, we examined pterostilbene's effects on hepatic gluconeogenic gene expression. Pterostilbene treatment significantly repressed dexamethasone-induced phosphoenol pyruvate carboxykinase (PEPCK) and glucose6-phosphatase (G6Pase) gene expression, and decreased glucose production in H4IIE cells. Taken together, our studies demonstrate that pterostilbene, a natural compound and PPAR-α agonist, modulate several AMPK-dependent metabolic functions. The results of the present study suggest that pterostilbene may have beneficial effects in the prevention and management of type 2 diabetes and related disorders. In this study, we found that pterostilbene activated AMP-activated kinase (AMPK) and increased the expression of fatty acid oxidation genes, including acyl CoA oxidase and carnitine palmitoyl transferase-1.