• Title/Summary/Keyword: Gluconeogenesis

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Lactobacillus acidophilus NS1 Reduces Phosphoenolpyruvate Carboxylase Expression by Regulating HNF4α Transcriptional Activity

  • Park, Sung-Soo;Yang, Garam;Kim, Eungseok
    • Food Science of Animal Resources
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    • v.37 no.4
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    • pp.529-534
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    • 2017
  • Probiotics have been known to reduce high-fat diet (HFD)-induced metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. We recently observed that Lactobacillus acidophilus NS1 (LNS1), distinctly suppresses increase of blood glucose levels and insulin resistance in HFD-fed mice. In the present study, we demonstrated that oral administration of LNS1 with HFD feeding to mice significantly reduces hepatic expression of phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme in gluconeogenesis which is highly increased by HFD feeding. This suppressive effect of LNS1 on hepatic expression of PEPCK was further confirmed in HepG2 cells by treatment of LNS1 conditioned media (LNS1-CM). LNS1-CM strongly and specifically inhibited $HNF4{\alpha}-induced$ PEPCK promoter activity in HepG2 cells without change of $HNF4{\alpha}$ mRNA levels. Together, these data demonstrate that LNS1 suppresses PEPCK expression in the liver by regulating $HNF4{\alpha}$ transcriptional activity, implicating its role as a preventive or therapeutic approach for metabolic diseases.

Lithium and exercise ameliorate insulin-deficient hyperglycemia by independently attenuating pancreatic α-cell mass and hepatic gluconeogenesis

  • Su-Ryun Jung;Ji-Hye Lee;Hanguk Ryu;Yurong Gao;Jaemin Lee
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.1
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    • pp.31-38
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    • 2024
  • As in type 1 diabetes, the loss of pancreatic β-cells leads to insulin deficiency and the subsequent development of hyperglycemia. Exercise has been proposed as a viable remedy for hyperglycemia. Lithium, which has been used as a treatment for bipolar disorder, has also been shown to improve glucose homeostasis under the conditions of obesity and type 2 diabetes by enhancing the effects of exercise on the skeletal muscles. In this study, we demonstrated that unlike in obesity and type 2 diabetic conditions, under the condition of insulin-deficient type 1 diabetes, lithium administration attenuated pancreatic a-cell mass without altering insulin-secreting β-cell mass, implying a selective impact on glucagon production. Additionally, we also documented that lithium downregulated the hepatic gluconeogenic program by decreasing G6Pase protein levels and upregulating AMPK activity. These findings suggest that lithium's effect on glucose metabolism in type 1 diabetes is mediated through a different mechanism than those associated with exercise-induced metabolic changes in the muscle. Therefore, our research presents the novel therapeutic potential of lithium in the treatment of type 1 diabetes, which can be utilized along with insulin and independently of exercise.

Branched-chain Amino Acids Reverse the Growth of Intrauterine Growth Retardation Rats in a Malnutrition Model

  • Zheng, Chuan;Huang, Chengfei;Cao, Yunhe;Wang, Junjun;Dong, Bing
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.11
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    • pp.1495-1503
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    • 2009
  • This experiment was conducted to determine the effect of dietary supplementation with BCAA (branched-chain amino acids: leucine, isoleucine and valine) on improving the growth of rats in a malnutritional IUGR (Intrauterine Growth Retardation) model, which was established by feeding restriction. In the experimental treatment, rats were fed purified diets supplemented with BCAA (mixed) during the whole gestation period, while arginine and alanine supplementation were set as the positive and negative control group, respectively. The results showed that, compared to the effect of alanine, BCAA reversed IUGR by increasing the fetus weights by 18.4% and placental weights by 18.0% while fetal numbers were statistically increased. Analysis of gene and protein expression revealed that BCAA treatment increased embryonic liver IGF-I expression; the uterus expressed higher levels of estrogen receptor-$\alpha$ (ER-$\alpha$) and progesterone receptor (PR), and the placenta expressed higher levels of IGF-II. Amino acid analysis of dam plasma revealed that BCAA supplementation effectively enhanced the plasma BCAA levels caused by the feed restriction. BCAA also enhanced the embryonic liver gluconeogenesis by augmenting the expression of two key enzymes, namely fructose-1,6-biphosphatase (FBP) and phosphoenolpyruvate carboxykinase (PEPCK). In conclusion, supplementation of BCAA increased litter size, embryonic weight and litter embryonic weight by improving the dam uterus and placental functions as well as increasing gluconeogenesis in the embryonic liver, which further provided energy to enhance the embryonic growth.

Anti-hyperglycemic effects and signaling mechanism of Perilla frutescens sprout extract

  • Kim, Da-Hye;Kim, Sang Jun;Yu, Kang-Yeol;Jeong, Seung-Il;Kim, Seon-Young
    • Nutrition Research and Practice
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    • v.12 no.1
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    • pp.20-28
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    • 2018
  • BACKGROUND/OBJECTIVES: Perilla frutescens (L.) Britton var. (PF) sprout is a plant of the labiate family. We have previously reported the protective effects of PF sprout extract on cytokine-induced ${\beta}-cell$ damage. However, the mechanism of action of the PF sprout extract in type 2 diabetes (T2DM) has not been investigated. The present study was designed to study the effects of PF sprout extract and signaling mechanisms in the T2DM mice model using C57BL/KsJ-db/db (db/db) mice. MATERIALS/METHODS: Male db/db mice were orally administered PF sprout extract (100, 300, and 1,000 mg/kg of body weight) or rosiglitazone (RGZ, positive drug, 1 mg/kg of body weight) for 4 weeks. Signaling mechanisms were analyzed using liver tissues and HepG2 cells. RESULTS: The PF sprout extract (300 and 1,000 mg/kg) significantly reduced the fasting blood glucose, serum insulin, triglyceride and total cholesterol levels in db/db mice. PF sprout extract also significantly improved glucose intolerance and insulin sensitivity, decreased hepatic gluconeogenic protein expression, and ameliorated histological alterations of the pancreas and liver. Levels of phosphorylated AMP-activated protein kinase (AMPK) protein expression also increased in the liver after treatment with the extract. In addition, an increase in the phosphorylation of AMPK and decrease in the phosphoenolpyruvate carboxykinase and glucose 6-phosphatase proteins in HepG2 cells were also observed. CONCLUSIONS: Our results sugges that PF sprout displays beneficial effects in the prevention and treatment of type 2 diabetes via modulation of the AMPK pathway and inhibition of gluconeogenesis in the liver.

Blood amino acids profile responding to heat stress in dairy cows

  • Guo, Jiang;Gao, Shengtao;Quan, Suyu;Zhang, Yangdong;Bu, Dengpan;Wang, Jiaqi
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.1
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    • pp.47-53
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    • 2018
  • Objective: The objective of this experiment was to investigate the effects of heat stress on milk protein and blood amino acid profile in dairy cows. Methods: Twelve dairy cows with the similar parity, days in milk and milk yield were randomly divided into two groups with six cows raised in summer and others in autumn, respectively. Constant managerial conditions and diets were maintained during the experiment. Measurements and samples for heat stress and no heat stress were obtained according to the physical alterations of the temperature-humidity index. Results: Results showed that heat stress significantly reduced the milk protein content (p<0.05). Heat stress tended to decrease milk yield (p = 0.09). Furthermore, heat stress decreased dry matter intake, the concentration of blood glucose and insulin, and glutathione peroxidase activity, while increased levels of non-esterified fatty acid and malondialdehyde (p<0.05). Additionally, the concentrations of blood Thr involved in immune response were increased under heat stress (p<0.05). The concentration of blood Ala, Glu, Asp, and Gly, associated with gluconeogenesis, were also increased under heat stress (p<0.05). However, the concentration of blood Lys that promotes milk protein synthesis was decreased under heat stress (p<0.05). Conclusion: In conclusion, this study revealed that more amino acids were required for maintenance but not for milk protein synthesis under heat stress, and the decreased availability of amino acids for milk protein synthesis may be attributed to competition of immune response and gluconeogenesis.

Gene Analysis Related Energy Metabolism of Leaf Expressed Sequence Tags Database of Korean Ginseng (Panax ginseng C.A. Meyer) (고려인삼(Panax ginseng C.A, Meyer)의 잎 ESTs database에서 Energy 대사 관련 유전자 분석)

  • Lee Jong-Il;Yoon Jae-Ho;Song Won-Seob;Lee Bum-Soo;In Jun-Gyo;Kim Eun-Jeong;Yang Deok-Chun
    • Korean Journal of Plant Resources
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    • v.19 no.1
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    • pp.174-179
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    • 2006
  • A cDNA library was constructed from leaf samples of 4-year-old Panax ginseng cultured in a field. 3,000 EST from a size selected leaf cDNA library were analyzed. The 349 of 2,896 cDNA clones has related with energy metabolism genes. The 349 known genes were categorized into nine groups according to their functional classification, aerobic respiration(48.4%), accessory proteins of electron transport and membrane associated energy conservation(17.2%), glycolysis and gluconeogenesis(3.4%), electron transport and membrane associated energy conservation(2.9%), respiration(2.0%), glycolysis methylglyoxal bypass(1.7%), metabolism of energy reserves(0.6%) and alcohol fermentation(0.3%).

Ginseng Leaf Extract Prevents High Fat Diet-Induced Hyperglycemia and Hyperlipidemia through AMPK Activation

  • Yuan, Hai-Dan;Kim, Sung-Jip;Quan, Hai-Yan;Huang, Bo;Chung, Sung-Hyun
    • Journal of Ginseng Research
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    • v.34 no.4
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    • pp.369-375
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    • 2010
  • This study evaluated the protective effects of ginseng leaf extract (GLE) against high fat-diet-induced hyperglycemia and hyperlipidemia, and explored the potential mechanism underlying these effects in C57BL/6J mice. The mice were randomly divided into four groups: normal control, high fat diet control (HFD), GLE-treated at 250 mg/kg, and GLE-treated at 500 mg/kg. To induce hyperglycemic and hyperlipidemic states, mice were fed a high fat diet for 6 weeks and then administered GLE once daily for 8 weeks. At the end of the treatment, we examined the effects of GLE on plasma glucose, lipid levels, and the expression of genes related to lipogenesis, lipolysis, and gluconeogenesis. Both GLE groups lowered levels of plasma glucose, insulin, triglycerides, total cholesterol, and non-esterified fatty acids when compared to those in HFD group. Histological analysis revealed significantly fewer lipid droplets in the livers of GLE-treated mice compared with HFD mice. To elucidate the mechanism, Western blots and RT-PCR were performed using liver tissue. Compared with HFD mice, GLE-treated mice showed higher levels of phosphorylation of AMP-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase, but no differences in the expression of lipogenic genes such as sterol regulatory element-binding protein 1a, fatty acid synthase, sterol-CoA desaturase 1 and glycerol-3-phosphate acyltransferase. However, the expression levels of lipolysis and fatty acid uptake genes such as peroxisome proliferator-activated receptor-$\alpha$ and CD36 were increased. In addition, phosphoenolpyruvate carboxykinase gene expression was decreased. These results suggest that GLE ameliorates hyperglycemia and hyperlipidemia by inhibiting gluconeogenesis and stimulating lipolysis, respectively, via AMPK activation.

A comparative study on the ultrastructurs of the imaginal wing discs of the wild type and the mutant vestigial of Drosophila melanogaster (노랑초파리의 야생형과 흔적날개 돌연변이체의 날개 성체원기 발달에 관한 전자현미경적 연구)

  • 이하규;이정주
    • The Korean Journal of Zoology
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    • v.26 no.1
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    • pp.29-40
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    • 1983
  • The differences in the electron microscopic fine structures of the wing imaginal discs of the vestigial (vg), wing mutant and wild type of Drosophila melanogaster were investigated. The materials used in this study were collected at ten hours intervals from the late third instar larvae of the both stocks. The fine structural changes during differentiation were as follows: 1. In wild type lipid droplets were coalesced and converted to glycogen, while no changes were observed in the mutatn vestigial. 2. Degeneration of the cells by phagocytosis were observed not only from the mutatn vestigial, but from the wild type. However, degenerative feature of the wild type was poor. 3. Dented structures of tracheole showed little differences between wild type and the mutant vestigial. But the tracheole diameter of the wild type became wider in the course of differentiation, while the mutant vestigial narrow. Although mutant vestigial develops normally during early embryogenesis, the late third instar larvae shows defficiency in gluconeogenesis, converting fatty acid to glycogen. This, together with the predominant cell degeneration by phagocytosis and poorly developed tracheole, seems to effect on the expression of the vestigial phenotype.

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Provision of a protein-rich supplement for grazing suckling female beef calves to improve productive performance and metabolic response

  • Moreno, Deilen S;Ortega, Roman M;Marquez, David C;Moreira, Thiago R;Santos, Edson J dos;Almeida, Daniel M de;Paulino, Mario F;Renno, Luciana N;Detmann, Edenio
    • Animal Bioscience
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    • v.35 no.8
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    • pp.1174-1183
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    • 2022
  • Objective: This study was conducted to evaluate the effects of the provision of a protein-rich supplement on productive performance, and metabolic profile on grazing suckling female beef calves in tropical conditions during 150 d of experimentation. Methods: Fifty-six Nellore suckling female calves, and their respective dams were distributed in a completely randomised design and made to undergo two treatments as follows: UNS (without supplementation), and SUP (supplementation with 5 g/kg body weight [BW] of a protein supplement). Throughout the experiment, animal performance and metabolic profile were evaluated. Also, ureagenesis and gluconeogenesis were assessed for gene expression. Results: SUP female calves showed a higher voluntary intake (p≤0.03) of the diet components evaluated, digestibility of organic matter (p≤0.02) and microbial nitrogen production (MICN; p≤0.02) compared to UNS female calves. In its turn, serum urea nitrogen (p≤0.01) and insulin-like growth factor-1 (p≤0.03) levels and ureagenesis (p≤0.04) increased in SUP female calves compared to UNS female calves. Blood glucose and triglyceride levels were not affected by supplementation. The average daily gain (ADG) from SUP female calves was higher (p≤0.02) compared with UNS female calves. However, supplementation did not affect the body measures of the animals. Conclusion: In summary, provision of a protein-rich supplement improves the intake and nutrients digestibility, ADG and final BW and increases metabolic indicators of the protein status in grazing suckling female beef calves in tropical conditions.