• Title/Summary/Keyword: hexokinase

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Anti-Diabetic Effects of an Ethanol Extract of Cassia Abbreviata Stem Bark on Diabetic Rats and Possible Mechanism of Its Action - Anti-diabetic Properties of Cassia abbreviata -

  • Bati, Keagile;Kwape, Tebogo Elvis;Chaturvedi, Padmaja
    • Journal of Pharmacopuncture
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    • v.20 no.1
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    • pp.45-51
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    • 2017
  • Objectives: This study aimed to evaluate the hypoglycemic effects of an ethanol extract of Cassia abbreviata (ECA) bark and the possible mechanisms of its action in diabetic albino rats. Methods: ECA was prepared by soaking the powdered plant material in 70% ethanol. It was filtered and made solvent-free by evaporation on a rotary evaporator. Type 2 diabetes was induced in albino rats by injecting 35 mg/kg body weight (bw) of streptozotocin after having fed the rats a high-fat diet for 2 weeks. Diabetic rats were divided into ECA-150, ECA-300 and Metformin (MET)-180 groups, where the numbers are the doses in mg.kg.bw administered to the groups. Normal (NC) and diabetic (DC) controls were given distilled water. The animals had their fasting blood glucose levels and body weights determined every 7 days for 21 days. Oral glucose tolerance tests (OGTTs) were carried out in all animals at the beginning and the end of the experiment. Liver and kidney samples were harvested for glucose 6 phosphatase (G6Pase) and hexokinase activity analyses. Small intestines and diaphragms from normal rats were used for ${\alpha}-glucosidase$ and glucose uptake studies against the extract. Results: Two doses, 150 and 300 mg/kg bw, significantly reduced the fasting blood glucose levels in diabetic rats and helped them maintain normal body weights. The glucose level in DC rats significantly increased while their body weights decreased. The 150 mg/kg bw dose significantly increased hexokinase and decreased G6Pase activities in the liver and the kidneys. ECA inhibited ${\alpha}-glucosidase$ activity and promoted glucose uptake in the rats' hemi-diaphragms. Conclusion: This study revealed that ECA normalized blood glucose levels and body weights in type 2 diabetic rats. The normalization of the glucose levels may possibly be due to inhibition of ${\alpha}-glucosidase$, decreased G6Pase activity, increased hexokinase activity and improved glucose uptake by muscle tissues.

Enzymatic properties of the N- and C-terminal halves of human hexokinase II

  • Ahn, Keun-Jae;Kim, Jong-Sun;Yun, Mi-Jin;Park, Jeon-Han;Lee, Jong-Doo
    • BMB Reports
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    • v.42 no.6
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    • pp.350-355
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    • 2009
  • Although previous studies on hexokinase (HK) II indicate both the N- and C-terminal halves are catalytically active, we show in this study the N-terminal half is significantly more catalytic than the C-terminal half in addition to having a significantly higher $K_m$ for ATP and Glu. Furthermore, truncated forms of intact HK II lacking its first N-terminal 18 amino acids ($\Delta$18) and a truncated N-terminal half lacking its first 18 amino acids ($\Delta$18N) have higher catalytic activity than other mutants tested. Similar results were obtained by PET-scan analysis using $^{18}F-FDG$. Our results collectively suggest that each domain of HK II possesses enzyme activity, unlike HK I, with the N-terminal half showing higher enzyme activity than the C-terminal half.

Melatonin Protects Chronic Kidney Disease Mesenchymal Stem/Stromal Cells against Accumulation of Methylglyoxal via Modulation of Hexokinase-2 Expression

  • Go, Gyeongyun;Yoon, Yeo Min;Yoon, Sungtae;Lee, Gaeun;Lim, Ji Ho;Han, Su-Yeon;Lee, Sang Hun
    • Biomolecules & Therapeutics
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    • v.30 no.1
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    • pp.28-37
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    • 2022
  • Treatment options for patients with chronic kidney disease (CKD) are currently limited; therefore, there has been significant interest in applying mesenchymal stem/stromal cell (MSC)-based therapy to treat CKD. However, MSCs harvested from CKD patients tend to show diminished viability and proliferation due to sustained exposure to uremic toxins in the CKD environment, which limits their utility for cell therapy. The application of melatonin has been demonstrated to improve the therapeutic efficacy of MSCs derived from and engrafted to tissues in patients suffering from CKD, although the underlying biological mechanism has not been elucidated. In this study, we observed overexpression of hexokinase-2 (HK2) in serum samples of CKD patients and MSCs harvested from an adenine-fed CKD mouse model (CKD-mMSCs). HK2 upregulation led to increased production levels of methylglyoxal (MG), a toxic metabolic intermediate of abnormal glycolytic processes. The overabundance of HK2 and MG was associated with impaired mitochondrial function and low cell proliferation in CKD-mMSCs. Melatonin treatment inhibited the increases in HK2 and MG levels, and further improved mitochondrial function, glycolytic metabolism, and cell proliferation. Our findings suggest that identifying and characterizing metabolic regulators such as HK2 in CKD may improve the efficacy of MSCs for treating CKD and other kidney disorders.

Anti-diabetic effect and effect on glucose-phosphorylase activities of the leaf of Eriobotryae folium on diabetes mellitus mice induced by interleukin-1β (비파엽(枇杷葉)의 항당뇨병약리활성(抗糖尿病藥理活性)과 IL-1β유발당뇨병(誘發糖尿病) 마우스의 췌장(膵臟) 인산화효소(燐酸化酵素)에 미치는 효과(效果)에 관(關)한 연구(硏究))

  • Yoon, Cheol-Ho;Jeong, Ji-Cheon;Kim, Cheorl-Ho
    • The Journal of Dong Guk Oriental Medicine
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    • v.7 no.1
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    • pp.75-86
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    • 1998
  • Studies were conducted on anti-dibetic effect of the water extract from leaves of Eriobotryae folium, which had been used in Korea as a remedy for dibetes. The extract was found to inhibit the increase in the plasma level of sugar bu the not the decrease in the plasma level of insulin in alloxan-induced dibetic rats. Also, we investigated the in vivo effect of an aqueous extract (referred to as EF) from Eriobotryae folium on glucokinase and hexokinase activities of diabetes mellitus induced by interleukin-$1{\beta}$ ($IL-1{\beta}$). After 1 week of $IL-1{\beta}$ injection, the levels of serum glucose concentration and insulin secretion were dramatically increased. However, the insulin secretion was decreased with administration of EF. The level of glucose concentration was decreased by EF administration. Furthermore, it was observed that EF was effective in recovering the levels of insulin secretion. Enzyme activities of the glucokinase and hexokinase, which are key enzymes of glucose phosphorylastion, were decreased by $IL-1{\beta}$. EF administration to the mice allowed proportional increasing by stimulation of induction of enzyme activities as high as normal group. These results suggested that EF is highly effective in treatment of diabetes mellitus induce by $IL-1{\beta}$.

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Comparisons between White Ginseng Radix and Rootlet for Antidiabetic Activity and Mechanism in KKAy Mice

  • Chung, Sung-Hyun;Choi, Chang-Geun;Park, Se-Ho
    • Archives of Pharmacal Research
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    • v.24 no.3
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    • pp.214-218
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    • 2001
  • The mechanisms responsible for the antidiabetic activity of both the white ginseng radix (Ginseng Radix Alba, GRA) and the rootlet (Cinseng Radix Palva, GRP) were investigated. After a four week oral administration, the fasting blood glucose levels in the GRA- and GRP-treated groups were lower when compared to the control group. To elucidate the hypoglycemic mechanism(s) of the ginseng radices, glucose absorption from the small intestine, hepatic hexokinase and glucose-6-phosphatase activities, in addition to PPAR-${\gamma}$ expression in adipose tissue were examined. The results strongly suggest that GRA can improve hyperglycemia in KKAy mice, possibly by blocking intestinal glucose absorption and inhibiting hepatic glucose-6-phosphatase, and GRP through the upregulation of adipocytic PPAR-$\gamma$ protein expression as well as inhibiting intestinal glucose absorption.

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Effects of Bombycis corpus on Streptozotocin-induced Diabetic Rats (Streptozotocin으로 유발된 당뇨쥐에 대한 백강잠(白?蠶)의 혈당 및 당대사 효소활성에 관한 효과)

  • Hyun, Min-Kyung;Sin, Won-Yong;Kim, Mi-Rang;Shin, Hyeon-Cheol;Yoon, Cheol-Ho;Jeong, Ji-Cheon;Jeong, Byoung-Mu
    • The Journal of Internal Korean Medicine
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    • v.25 no.2
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    • pp.288-297
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    • 2004
  • Objective : This study was undertaken to investigate how Bombycis corpus (BC) effects the development and progress of complications occurring in Diabetes Mellitus (DM). Methods : Laboratory rats were seperated into three groups; normal, rats with DM and treated with BC, and rats with DM and not treated. In this study DM was experimentally induced through injection of streptozotocin. The BC treated group was given BC extract p.o. for 15 days. Then, The activities of glucose phosphatic enzymes and polyol pathway channels were observed. Results : The blood glucose level greatly increased in the DM groups after injection of streptoztocin, but it significantly decreased in the BC treated group. Significantly enhanced levels of serum insulin levels were seen in the BC treated group, while supressed levels were seen in the untreated DM group. Weight was recovered by the BC treated group, matching the normal group. Decreased enzyme activity of aldose reductase, sorbitol dehydrogenase and glucose-6-phosphatase were seen in BC treated diabetic rats. Increased enzyme activity, of the glucokinase and hexokinase were seen in BC treated diabetic rats. Conclusions : This study suggests that BC normalized the blood glucose and serum insulin levels destablized by DM. Because increased activity of glucose phosphatic enzymes, glucokinase and hexokinase, and decreased glucose-6-phosphatase activity, and suppression of polyol pathway enzymes, aldose reductase and sorbitol dehydrogenase, were all seen, these observations suggest that BC suppresses blood glucose levels and prevents complications due to DM.

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Decreased glucose uptake by hyperglycemia is regulated by different mechanisms in human cancer cells and monocytes (사람 암세포와 단핵세포에서 고포도당 농도에 의한 FDG 섭취 저하의 서로 다른 기전)

  • Kim, Chae-Kyun;Chung, June-Key;Lee, Yong-Jin;Hong, Mee-Kyoung;Jeong, Jae-Min;Lee, Dong-Soo;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.2
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    • pp.110-120
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    • 2002
  • To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied $[^{18}F]$ fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5 - 10.8 mU/mg), while SNU-C5 and monocytes showed lower range of hexokinase activity (4.3 - 6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes.

Effect of Fermented Small Soybean Powder Mixed with Mulberry Leaf on Metabolic Improvement and Hexokinase Activity in Streptozotocin-induced Diabetic Rats

  • Kim, Sun-Mi;Han, Jin-Chul;Park, Hum-Dai;Ko, Ki-Sung;Lee, Dae-Hoon;Kim, Sung-Min;Kwon, Dong-Yeul;Kim, Jin-Sook;Kim, Ok-Hee;Hwang, Jin-Bong;Gung, Bae-Nahm;Choo, Young-Kug
    • Nutritional Sciences
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    • v.9 no.2
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    • pp.97-105
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    • 2006
  • Beans are well known to be high-protein diets. Bean seeds contain arginine, lysine, or glycine-rich proteins which are effective to maintain lower glucose levels. In this study, the synergistic effect of fermented small soybean (Chounggukjang) and mulberry leaf on metabolism and hexokinase activity was investigated in streptozotocin (STZ)-induced diabetic rats. We divided 8 groups as follows: non-diabetic rat group fed with only water diet (NC: control), and STZ-induced diabetic rat groups fed with water (DC), fermented Rhynchosia Nulubilis (Bbc), fermented Glycine max Merr (Ybc), Bbc and YBc (BYbc), mulberry leaf and Bbc (MBbc), mulberry leaf and Ybc (MYbc), or the mulberry leaf, Bbc, and Ybc (MBYbc). Diabetes mellitus was induced in rats by subcutaneous STZ administration (70 mg/kg of body weight). All diet groups were fed with Chounggukjang in a powder form. Three ml of Chounggukjang solution (0.75 mg per gram of body weight) dissolved in distilled water was orally administered to all rat groups after STZ administration except for NC rat group. In groups fed with fermented soybeans, the body weight (increased), food efficiency ratio (FER) (increased), glucose level (decreased) and hexokinase (HK) activity (increased) significantly differed to NC. Among them, particularly in the groups fed with both fermented soybeans and mulberry leaf, kidney weight significantly decreased, whereas HK activity significantly increased compared to DC. These results suggest that Chounggukjang of both fermented soybeans and mulberry leaf is potentially used as an effective functional food to prevent diabetes complications.

The Effect of Ginseng Saponin Fraction on Several Glycolytic Enzymes of Yeast Cell (인삼 사포닌이 효모의 몇 가지 해당 효소에 미치는 영향)

  • 강철호;주충노
    • Journal of Ginseng Research
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    • v.10 no.2
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    • pp.200-208
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    • 1986
  • It was attempted in this study to investigate the effect of ginseng saponin on several glycolytic enzymes of yeast cell and the following results were obtained. The amount of $CO_2$formed during the incubation of yeast cells in medium containing saponin fraction of Panax ginseng C.A. Meyer was greater than that of control cells and found that the $CO_2$ formation was greatest when the cells were grown in the medium containing 10$^{-3}$% of the saponin fraction, at which the uptake of inorganic phosphate and glucose consumption were also increased. Radioactivity study of several glycolytic intermediates of yeast cells cultured in the medium containing [U-$^{14}$C]-glucose showed that the radioactivity of fructose 6-phosphate of test cells was as much as 1.6times that of control group. On the other hand, the radioactivity of pyruvate of test cells was considerably decreased compared to control. Investigation of the effect of ginseng saponin on yeast hexokinase, phosphoglucose isomers, pyruvate kinase and perverted decarboxylase in vitro showed that the maximum activities of the above enzymes were observed when the concentration of ginseng saponin was 10-$^{-5}$% in the reaction mixture. It seemed that the ginseng saponin stimulated both glycolytic enzymes such as hexokinase, phosphoglucose isomers and perverted decarboxylase significantly.

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