• 한국축산식품학회지
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• 제37권4호
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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.

• Asian-Australasian Journal of Animal Sciences
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• 제23권1호
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• pp.47-51
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• 2010

The objective of this study was to understand changes of plasma metabolites, hormones, and mRNA level of cytoplasmic phosphoenolpyruvate carboxykinase (PEPCK-C) in liver in spontaneous clinical ketosis; 10 clinically ketotic cows and 10 healthy cows were chosen from the same dairy farm. Eleven blood parameters and liver fat content were measured in all cows, and mRNA levels of PEPCK-C in liver were measured by semi-quantitative reverse transcription (RT) polymerase chain reaction (PCR). In ketotic cows, concentration of plasma glucose decreased (p<0.01), concentration of plasma nonesterified fatty acids (NEFA) and $\beta$-hydroxybutyric acid (BHBA) increased (p<0.01), liver fat content (18.8% wet weight) and activity of plasma aspartate aminotransferase (AST) increased (p<0.01), but concentration of plasma total bilirubin (TBIL), $\gamma$-glutamyl transpeptidase ($\gamma$-GT), and cholinesterase (CHE) increased (p>0.05). In addition, concentration of plasma insulin decreased (p<0.05), concentration of plasma glucagons decreased (p>0.05), and mRNA level of PEPCK-C in liver increased (p<0.05). It is concluded that the adaptative changes of metabolites, hormones, and mRNA level of PEPCK-C in ketotic cows were in favor of the enhancement of gluconeogenesis, the decrease of fat mobilization and the relief of ketosis, but these were still inadequate to relieve ketosis.

• Animal Bioscience
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• 제36권11호
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• pp.1693-1699
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• 2023

Objective: Cows that are nursing get around 80% of their glucose from liver gluconeogenesis. Propionate, a significant precursor of liver gluconeogenesis, can regulate the key genes involved in hepatic gluconeogenesis expression, but its precise effects on the activity of enzymes have not yet been fully elucidated. Therefore, the aim of this study was to investigate the effects of propionate on the activity, gene expression, and protein abundance of the key enzymes involved in the gluconeogenesis of dairy cow hepatocytes. Methods: The hepatocytes were cultured and treated with various concentrations of sodium propionate (0, 1.25, 2.50, 3.75, and 5.00 mM) for 12 h. Glucose content in the culture media was determined by an enzymatic coloring method. The activities of gluconeogenesis related enzymes were determined by enzyme linked immunosorbent assay kits, and the levels of gene expression and protein abundance of the enzymes were detected by real-time quantitative polymerase chain reaction and Western blot, respectively. Results: Propionate supplementation considerably increased the amount of glucose in the culture medium compared to the control (p<0.05); while there was no discernible difference among the various treatment concentrations (p>0.05). The activities of cytoplasmic phosphoenolpyruvate carboxylase (PEPCK1), mitochondrial phosphoenolpyruvate carboxylase (PEPCK2), pyruvate carboxylase (PC), and glucose-6-phosphatase (G6PC) were increased with the addition of 2.50 and 3.75 mM propionate; the gene expressions and protein abundances of PEPCK1, PEPCK2, PC, and G6PC were increased by 3.75 mM propionate addition. Conclusion: Propionate encouraged glucose synthesis in bovine hepatocytes, and 3.75 mM propionate directly increased the activities, gene expressions and protein abundances of PC, PEPCK1, PEPCK2, and G6PC in bovine hepatocytes, providing a theoretical basis of propionate-regulating gluconeogenesis in bovine hepatocytes.

• Animal cells and systems
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• 제16권2호
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• pp.87-94
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• 2012

Nur77 is a member of the nuclear receptor 4A (NR4A) subgroup, which has been implicated in energy metabolism. Although Nur77 is found in adipose tissue, where TR4 plays a key role in lipid homeostasis, the role of Nur77 in adipogenesis is still controversial. Although the Nur77 responsive element (AAAGGTCA) is partially overlapped with TR4-binding sites (AGGTCA $n$ AGGTCA: $n$=0-6), the regulatory role of Nur77 in TR4 function associated with adipocyte biology remains unclear. Here, we found that Nur77 inhibits adipogenesis and TR4 transcriptional activity. Treatment with a Nur77 agonist, 1,1-bis(3'-indolyl)-1-($p$-anisyl)-methane, during 3T3-L1 adipocyte differentiation reduced adipogenesis. In reporter gene analysis, Nur77 specifically suppressed TR4 transcription activity but had little effect on $PPAR{\gamma}$ transcription activity. Consistently, Nur77 also suppressed TR4-induced promoter activity of the TR4 target gene PEPCK, which is known to be important for glyceroneogenesis in adipose tissue. Furthermore, Nur77 suppressed TR4 binding to TR4 response elements without direct interaction with TR4, suggesting that Nur77 may inhibit TR4 transcription activity via binding competition for TR4-binding sites. Furthermore, DIM-C-$pPhOCH_3$ substantially suppressed TR4-induced PEPCK expression in 3T3-L1 adipocytes. Together, our data demonstrate that Nur77 plays an inhibitory role in TR4-induced PEPCK expression in 3T3-L1 adipocytes.

• Nutrition Research and Practice
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• 제10권1호
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• pp.11-18
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• 2016

BACKGROUND/OBJECTIVES: Type 2 diabetes (T2D) is more frequently diagnosed and is characterized by hyperglycemia and insulin resistance. $\small{D}$-xylose, a sucrase inhibitor, may be useful as a functional sugar complement to inhibit increases in blood glucose levels. The objective of this study was to investigate the anti-diabetic effects of $\small{D}$-xylose both in vitro and stretpozotocin (STZ)-nicotinamide (NA)-induced models in vivo. MATERIALS/METHODS: Wistar rats were divided into the following groups: (i) normal control; (ii) diabetic control; (iii) diabetic rats supplemented with a diet where 5% of the total sucrose content in the diet was replaced with $\small{D}$-xylose; and (iv) diabetic rats supplemented with a diet where 10% of the total sucrose content in the diet was replaced with $\small{D}$-xylose. These groups were maintained for two weeks. The effects of $\small{D}$-xylose on blood glucose levels were examined using oral glucose tolerance test, insulin secretion assays, histology of liver and pancreas tissues, and analysis of phosphoenolpyruvate carboxylase (PEPCK) expression in liver tissues of a STZ-NA-induced experimental rat model. Levels of glucose uptake and insulin secretion by differentiated C2C12 muscle cells and INS-1 pancreatic ${\beta}$-cells were analyzed. RESULTS: In vivo, $\small{D}$-xylose supplementation significantly reduced fasting serum glucose levels (P < 0.05), it slightly reduced the area under the glucose curve, and increased insulin levels compared to the diabetic controls. $\small{D}$-xylose supplementation enhanced the regeneration of pancreas tissue and improved the arrangement of hepatocytes compared to the diabetic controls. Lower levels of PEPCK were detected in the liver tissues of $\small{D}$-xylose-supplemented rats (P < 0.05). In vitro, both 2-NBDG uptake by C2C12 cells and insulin secretion by INS-1 cells were increased with $\small{D}$-xylose supplementation in a dose-dependent manner compared to treatment with glucose alone. CONCLUSIONS: In this study, $\small{D}$-xylose exerted anti-diabetic effects in vivo by regulating blood glucose levels via regeneration of damaged pancreas and liver tissues and regulation of PEPCK, a key rate-limiting enzyme in the process of gluconeogenesis. In vitro, $\small{D}$-xylose induced the uptake of glucose by muscle cells and the secretion of insulin cells by ${\beta}$-cells. These mechanistic insights will facilitate the development of highly effective strategy for T2D.

• Biotechnology and Bioprocess Engineering:BBE
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• 제7권2호
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• pp.95-99
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• 2002

A pckA gene encoding phosphoenolpyruvate carboxykinase (PEPCK) was cloned and sequenced from the succinic acid producing bacterium Mannheimia succiniciproducens MBEL55E. The gene encoded a 538 residue polypeptide with a calculated molecular mass of 58.8 kDa and a calculated pI of 5.03. The deduced amino acid sequence of the M. succiniciprodutens MBEL55E PEPCK was similar to those of all known ATP-dependent PEPCKS.

• 한국양식학회:학술대회논문집
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• 한국양식학회 2005년도 춘계학술발표대회 논문요약집
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• pp.100-101
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• 2005

• Journal of Ginseng Research
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• 제31권2호
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• pp.79-85
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• 2007

진세노사이드의 인슐린 분비 활성을 비교해 본 결과 PPD 계열 진세노사이드가 인슐린의 분비를 촉진하는 경향을 보였으며, 그 중에서도 CK의 인슐린 분비 촉진 효과가 가장 뛰어났다. CK는 RIN-m5F cell line과 일차 배양한 췌장 소도 세포에서 용량 의존적으로 인슐린의 분비를 촉진하였고 이러한 CK의 인슐린 분비 촉진 기전은 ATP-sensitive $K^+$ 채널의 봉쇄에 의한 것임을 확인하였다. H4IIE cell line에서 간 세포내 당신생과 관련된 효소의 발현을 측정한 결과 CK는 dexamethasone/cAMP에 의한 PEPCK 와 G6Pase의 발현을 억제하였다. 이로 미루어 볼 때, CK는 간에서 당의 신생을 억제하여 공복 시 혈당을 감소시킬 수 있음을 시사하였다. 또한 3T3-L1 cell line에서 TG의 함량과 $PPAR-{\gamma}$ 유전자의 발현에 미치는 영향을 살펴본 결과 CK는 $PPAR-{\gamma}$의 발현을 억제하여 결과 지방세포의 분화를 억제하였다. 결론적으로 CK는 췌장에서 ATP-sensitive $K^+$ channel을 봉쇄함으로 인슐린 분비를 촉진시키고 또한 간세포에서 당 신생을 억제함으로 식후 및 공복 시 혈당을 감소시킬 것으로 기대된다.

• 한국양식학회:학술대회논문집
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• 한국양식학회 2006년도 수산관련학회 공동학술대회 발표요지집
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• pp.361-362
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• 2006

• Archives of Pharmacal Research
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• 제29권3호
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• pp.256-264
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• 2006

Salicornia herbacea L. (Chenopodiaceae) has been used as a seasoned vegetable by living in coastal areas. S. herbacea (SH) has been demonstrated to stimulate cytokine production, nitric oxide release, and to show anti-oxidative effect. In a series of investigations to develop potential anti-diabetic and/or anti-hyperlipidemic agents from Korean indigenous plants, 50% ethanol extract of Salicornia herbacea was found to prevent the onset of the hyperglycemia and hyperlipidemia induced by high fat diet in ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice were to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high fat diet with either 350 mg/kg, 700 mg/kg of SH (SH350 and SH700) or 250 mg/kg of met-formin (MT250) for a 10-week period. SH not only reduced body weight but also corrected associated hyperglycemia and hyperlipidemia in a dose dependent manner. SH exerted beneficial effects on the plasma glucose and lipid homeostasis possibly ascribed to its specific effects on lipogenesis related genes (SREBP1a, FAS, GAPT), and PEPCK, glucose 6-phosphatase gene expressions in liver. Ethanol extract of S. herbacea has potential as a preventive agent for type 2 diabetes (and possibly hyperlipidemia) and deserves future clinical trial.