• Title/Summary/Keyword: Insulin secretion

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Disorders of Potassium Metabolism (칼륨 대사 장애)

  • Lee, Joo-Hoon
    • Childhood Kidney Diseases
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    • v.14 no.2
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    • pp.132-142
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    • 2010
  • Hypokalemia usually reflects total body potassium deficiency, but less commonly results from transcellular potassium redistribution with normal body potassium stores. The differential diagnosis of hypokalemia includes pseudohypokalemia, cellular potassium redistribution, inadequate potassium intake, excessive cutaneous or gastrointestinal potassium loss, and renal potassium wasting. To discriminate excessive renal from extrarenal potassium losses as a cause for hypokalemia, urine potassium concentration or TTKG should be measured. Decreased values are indicative of extrarenal losses or inadequate intake. In contrast, excessive renal potassium losses are expected with increased values. Renal potassium wasting with normal or low blood pressure suggests hypokalemia associated with acidosis, vomiting, tubular disorders or increased renal potassium secretion. In hypokalemia associated with hypertension, plasam renin and aldosterone should be measured to differentiated among hyperreninemic hyperaldosteronism, primary hyperaldosteronism, and mineralocorticoid excess other than aldosterone or target organ activation. Hypokalemia may manifest as weakness, seizure, myalgia, rhabdomyolysis, constipation, ileus, arrhythmia, paresthesias, etc. Therapy for hypokalemia consists of treatment of underlying disease and potassium supplementation. The evaluation of hyperkalemia is also a multistep process. The differential diagnosis of hyperkalemia includes pseudohypokalemia, redistribution, and true hyperkalemia. True hyperkalemia associated with decreased glomerular filtration rate is associated with renal failure or increased body potassium contents. When glomerular filtration rate is above 15 mL/min/$1.73m^2$, plasma renin and aldosterone must be measured to differentiate hyporeninemic hypoaldosteronism, primary aldosteronism, disturbance of aldosterone action or target organ dysfunction. Hyperkalemia can cause arrhythmia, paresthesias, fatigue, etc. Therapy for hyperkalemia consists of administration of calcium gluconate, insulin, beta2 agonist, bicarbonate, furosemide, resin and dialysis. Potassium intake must be restricted and associated drugs should be withdrawn.

Ginsenoside $Rg_3$ Increases the ATP-sensitive $K^+$ Channel Activity in the Smooth Muscle of the Rabbit Coronary Artery

  • Chung Induk;Lee Jeong-Sun
    • Journal of Ginseng Research
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    • v.23 no.4
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    • pp.235-238
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    • 1999
  • ATP-sensitive $K^+$ channels $(K_{ATP})$ are expressed in vascular smooth muscle cells, skeletal muscle cells, pancreatic ${\beta}$ cells, neurons and epithelial cells. $K_{ATP}$ contributes to regulate membrane potential to control vascular tone, to protect myocardial ischemia, and to regulate insulin secretion in pancreatic ${\beta}$ cells. We previously demonstrated that ginseng saponins and ginsenoside $Rg_3$ activated maxi $Ca^{2+}-activated\;K^+$ channel, and this might cause vasodilation. Because $K_{ATP}$ plays an important roles to regulate the resting membrane potential in vascular smooth muscle cells, we investigated whether ginsenoside $Rg_3$ produces vasodilation by activating $K_{ATP}$ We showed in this study that $K_{ATP}$ is expressed in rabbit coronary artery smooth muscle cells. $K_{ATP}$ was inwardly rectifying and was inhibited by intemal application of ATP. Micromolar minoxidil activated, but glyburide inhibited the activity of $K_{ATP}$ Ginsenoside $Rg_3$ relieved inactivaiton of whole-cell $K_{ATP}$ current without affecting the peak amplitude of $K_{ATP}$ currents presumably due to more opening of the channels.

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Effect of In Vitro Antioxidant Properties and Extract of Corn Husk on Serum Lipids in Mice (옥수수 껍질 분말의 In Vitro 에서의 항산화 특성과 고지방식이로 유도된 Mice의 혈청지질 수준에 미치는 영향)

  • Shin, Kyung-Ok;Kim, Yong-Hwan;Lee, Ki-Won;Choi, Kyung-Soon
    • Journal of the East Asian Society of Dietary Life
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    • v.25 no.2
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    • pp.261-269
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    • 2015
  • This study was performed to verify the effects of corn husk powder on serum lipid levels of high-fat diet-induced mice from a nutritional viewpoint. Powder of corn husks has been used as a folk remedy from ancient times in Korea. In the case of corn husk measurement of TPC (p<0.05), ABTS+ radical scavenging activity of trolox (p<0.05), DPPH radical scavenging activity (p<0.05), and measured value of FRAP (p<0.0001) were higher in ethanol extract than water extract. Weight of livers was significantly higher in the control group and high-fat diet group compared to groups fed 10% and 20% corn husk powders with high-fat diet (p<0.0001). For blood HDL-cholesterol concentration, mice fed 10% corn husk powder with high-fat diet ($160.00{\pm}16.17mg/dL$) showed significantly higher levels compared with the other three groups (p<0.05). Mice fed 10% and 20% corn husk powders with high-fat diet showed high numerical values of $13.50{\pm}2.51$ and $11.25{\pm}2.87mg/dL$, respectively. For triglyceride concentration in blood, mice fed 10% ($83.50{\pm}19.30mg/dL$) and 20% ($88.50{\pm}22.25$) corn husk powder with high-fat diet showed very low levels compared to the control group and high-fat diet group. In the case of leptin, the high-fat diet group showed a significantly high level of $5.88{\pm}3.53ng/dL$. Groups fed 10% and 20% corn husks with high-fat diet showed low numerical values of $2.72{\pm}2.34ng/dL$ and $1.10{\pm}0.62ng/dL$, respectively (p<0.05). Corn husk powder increased high HDL-cholesterol concentration in blood while lowering triglyceride concentration and leptin secretion. Therefore, powder of corn husks has utility in the food industry and food processing.

Enhanced antidiabetic efficacy and safety of compound K/β-cyclodextrin inclusion complex in zebrafish

  • Nam, Youn Hee;Le, Hoa Thi;Rodriguez, Isabel;Kim, Eun Young;Kim, Keonwoo;Jeong, Seo Yule;Woo, Sang Ho;Lee, Yeong Ro;Castaneda, Rodrigo;Hong, Jineui;Ji, Min Gun;Kim, Ung-Jin;Hong, Bin Na;Kim, Tae Woo;Kang, Tong Ho
    • Journal of Ginseng Research
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    • v.41 no.1
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    • pp.103-112
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    • 2017
  • Background: 20(S)-Protopanaxadiol 20-O-D-glucopyranoside, also called compound K (CK), exerts antidiabetic effects that are mediated by insulin secretion through adenosine triphosphate (ATP)-sensitive potassium ($K_{ATP}$) channels in pancreatic ${\beta}$-cells. However, the antidiabetic effects of CK may be limited because of its low bioavailability. Methods: In this study, we aimed to enhance the antidiabetic activity and lower the toxicity of CK by including it with ${\beta}$-cyclodextrin (CD) (CD-CK), and to determine whether the CD-CK compound enhanced pancreatic islet recovery, compared to CK alone, in an alloxan-induced diabetic zebrafish model. Furthermore, we confirmed the toxicity of CD-CK relative to CK alone by morphological changes, mitochondrial damage, and TdT-UTP nick end labeling (TUNEL) assays, and determined the ratio between the toxic and therapeutic dose for both compounds to verify the relative safety of CK and CD-CK. Results: The CD-CK conjugate ($EC_{50}=2.158{\mu}M$) enhanced the recovery of pancreatic islets, compared to CK alone ($EC_{50}=7.221{\mu}M$), as assessed in alloxan-induced diabetic zebrafish larvae. In addition, CD-CK ($LC_{50} =20.68{\mu}M$) was less toxic than CK alone ($LC_{50}=14.24{\mu}M$). The therapeutic index of CK and CD-CK was 1.98 and 9.58, respectively. Conclusion: The CD-CK inclusion complex enhanced the recovery of damaged pancreatic islets in diabetic zebrafish. The CD-CK inclusion complex has potential as an effective antidiabetic efficacy with lower toxicity.

Effect of Circuit Training on Aging-related Hormones in Obese Middle-aged Women (서킷 트레이닝 비만 중년 여성의 노화 관련 호르몬에 미치는 영향)

  • Son, Won-Mok;Kwak, Yi-Sub;Kim, Gun-Do;Ha, Min-Sung;Park, Song-Young;Sung, Gi-Dong
    • Journal of Life Science
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    • v.27 no.9
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    • pp.1047-1051
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    • 2017
  • Due to aging, the physical fitness of middle-aged women decreases after menopause. This results in increased body fat and reduced lean body mass, both of which can lead to obesity. This phenomenon is accompanied by changes in hormone secretion in the body. The purpose of this study was to analyze the effects of circuit training on aging-related hormones in obese middle-aged women. The subjects were 20 obese middle-aged women. The subjects were divided into two groups: a circuit training group (n=10) and nonexercise control group (n=10). Growth hormone (GH), insulin-like growth factor-1 (IGF-1), estrogen, and DHEA-S were measured before and after the circuit training program. The circuit training group performed circuit training for 12 weeks, three times per week. Exercise intensity was increased gradually from 60% to 80% of heart rate reserve every 6 weeks. In the circuit training group, at the end of the 12-week training program, the IGF-1 levels were significantly increased compared to pre-exercise levels, and they were higher than those of the control group. GH levels were also significantly increased in the circuit training group, but the differences were not statistically significant. DHEA-S was significantly increased in the circuit training group, but the difference was not statistically significant. The results showed that circuit training improved aging-related hormones levels in obese middle-aged women.

Isolation of Citrus Peel Flavonoid Bioconversion Microorganism and Inhibitory Effect on the Oxidative Damage in Pancreatic Beta Cells (진피 플라보노이드 생물전환 균주 분리 및 췌장 베타세포에 대한 산화적 손상 억제 효과)

  • Park, Chi-Deok;Jung, Hee-Kyung;Park, Chang-Ho;Jung, Yoo-Seok;Hong, Joo-Heon;Ko, Hee-Sun;Kang, Dong-Hee;Kim, Hyun-Soo
    • KSBB Journal
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    • v.27 no.1
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    • pp.67-74
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    • 2012
  • In this study, the optimum conditions of fermentation were determined by isolating the microorganisms with the ability to bioconvert the Citrus peel flavonoid, and the effect of the fermented Citrus peel extract which was bioconverted on the oxidative damage of HIT-T15 cell was investigated. The Aureobasidium pullulans Y-12 was isolated and identified with the strains having bioconversion activity. The fermentation conditions for bioconversion activity were confirmed to be optimal when culturing for three days at $25^{\circ}C$, 150 rpm in a culture medium containing 5% Citrus peel power and 0.8% casitone. As a result of bioconversion, 32.8 mg/g and 21.5 mg/g of naringenin and hesperetin, which were aglycone flavones, were produced respectively. Also in the flavonoid content, it was confirmed that FCP produced 154.8 mg/g while CP produced 33.7 mg/g, thus producing more by approximately 4.6 times. As a result of treating FCP and CP after inducing the oxidative damage for HIT-T15 cell by treating the deoxy-D-ribose with $IC_{50}$ (38 mM) concentration, the surviving rate was recovered to 90% for FCP treatments in the 0.01 mg/mL concentration and for CP treatments in the 0.025 mg/mL concentration. Also in the insulin secretion rate, FCP treatments increased by 206% and CP treatments by 132% when treated in the 0.1 mg/mL concentration. As the bioconverted FCP can inhibit the oxidative damage of HIT-T15 cell in the low concentration, it was considered its usability as the functional material for prevention of the type 2 diabetes.

Mitochondrial Ca2+ Uptake Relieves Palmitate-Induced Cytosolic Ca2+ Overload in MIN6 Cells

  • Ly, Luong Dai;Ly, Dat Da;Nguyen, Nhung Thi;Kim, Ji-Hee;Yoo, Heesuk;Chung, Jongkyeong;Lee, Myung-Shik;Cha, Seung-Kuy;Park, Kyu-Sang
    • Molecules and Cells
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    • v.43 no.1
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    • pp.66-75
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    • 2020
  • Saturated fatty acids contribute to β-cell dysfunction in the onset of type 2 diabetes mellitus. Cellular responses to lipotoxicity include oxidative stress, endoplasmic reticulum (ER) stress, and blockage of autophagy. Palmitate induces ER Ca2+ depletion followed by notable store-operated Ca2+ entry. Subsequent elevation of cytosolic Ca2+ can activate undesirable signaling pathways culminating in cell death. Mitochondrial Ca2+ uniporter (MCU) is the major route for Ca2+ uptake into the matrix and couples metabolism with insulin secretion. However, it has been unclear whether mitochondrial Ca2+ uptake plays a protective role or contributes to lipotoxicity. Here, we observed palmitate upregulated MCU protein expression in a mouse clonal β-cell, MIN6, under normal glucose, but not high glucose medium. Palmitate elevated baseline cytosolic Ca2+ concentration ([Ca2+]i) and reduced depolarization-triggered Ca2+ influx likely due to the inactivation of voltage-gated Ca2+ channels (VGCCs). Targeted reduction of MCU expression using RNA interference abolished mitochondrial superoxide production but exacerbated palmitate-induced [Ca2+]i overload. Consequently, MCU knockdown aggravated blockage of autophagic degradation. In contrast, co-treatment with verapamil, a VGCC inhibitor, prevented palmitate-induced basal [Ca2+]i elevation and defective [Ca2+]i transients. Extracellular Ca2+ chelation as well as VGCC inhibitors effectively rescued autophagy defects and cytotoxicity. These observations suggest enhanced mitochondrial Ca2+ uptake via MCU upregulation is a mechanism by which pancreatic β-cells are able to alleviate cytosolic Ca2+ overload and its detrimental consequences.

Metabolomic analysis of healthy human urine following administration of glimepiride using a liquid chromatography-tandem mass spectrometry

  • Do, Eun Young;Gwon, Mi-Ri;Kim, Bo Kyung;Ohk, Boram;Lee, Hae Won;Kang, Woo Youl;Seong, Sook Jin;Kim, Hyun-Ju;Yoon, Young-Ran
    • Translational and Clinical Pharmacology
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    • v.25 no.2
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    • pp.67-73
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    • 2017
  • Glimepiride, a third generation sulfonylurea, is an antihyperglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an untargeted urinary metabolomic analysis was performed to identify endogenous metabolites affected by glimepiride administration. Urine samples of twelve healthy male volunteers were collected before and after administration of 2 mg glimepiride. These samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then subjected to multivariate data analysis including principal component analysis and orthogonal partial least squares discriminant analysis. Through this metabolomic profiling, we identified several endogenous metabolites such as adenosine 3', 5'-cyclic monophosphate (cAMP), quercetin, tyramine, and urocanic acid, which exhibit significant metabolomic changes between pre- and posturine samples. Among these, cAMP, which is known to be related to insulin secretion, was the most significantly altered metabolite following glimepiride administration. In addition, the pathway analysis showed that purine, tyrosine, and histidine metabolism was affected by pharmacological responses to glimepiride. Together, the results suggest that the pharmacometabolomic approach, based on LC-MS/MS, is useful in understanding the alterations in biochemical pathways associated with glimepiride action.

Anti-obesity Effect of the Flavonoid Rich Fraction from Mulberry Leaf Extract (뽕잎 추출물 기원 Flavonoid Rich Fraction의 항비만효과)

  • Go, Eun Ji;Ryu, Byung Ryeol;Yang, Su Jin;Baek, Jong Suep;Ryu, Su Ji;Kim, Hyun Bok;Lim, Jung Dae
    • Korean Journal of Medicinal Crop Science
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    • v.28 no.6
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    • pp.395-411
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    • 2020
  • Background: This study investigated the anti-obesity effect of the flavonoid rich fraction (FRF) and its constituent, rutin obtained from the leaf of Morus alba L., on the lipid accumulation mechanism in 3T3-L1 adipocyte and C57BL/6 mouse models. Methods and Results: In Oil Red O staining, FRF (1,000 ㎍/㎖) treatments showed inhibition rate of 35.39% in lipid accumulation compared to that in the control. AdipoRedTM assay indicated that the triglyceride content in 3T3-L1 adipocytes treated with FRF (1,000 ㎍/㎖) was reduced to 23.22%, and free glycerol content was increased to 106.04% that of the control. FRF and its major constituent, rutin affected mRNA gene expression. Rutin contributed to the inhibition of Sterol regulatory element binding protein-1c (SREBP-1c) gene expression, and inhibited the transcription factors SREBP-1c, peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). In addition, the effect of FRF administration on obesity development in C57BL/6 mice fed high-fat diet (HFD) was investigated. FRF suppressed weight gain, and reduced liver triglyceride and leptin secretion. FRF exerted potential anti-inflammatory effects by improving insulin resistance and adiponectin levels, and could thus be used to help counteract obesity. The mRNA expressions of PPAR-γ, FAS, ACC, and CPT-1 were determined in liver tissue. Quantitative real-time PCR analysis was also performed to evaluate the expression of IL-1β, IL-6, and TNF-α in epididymal adipose tissue. Compared to the control group, mice fed the HFD showed the up-regulation in PPAR-γ, FAS, IL-6, and TNF-α genes, and down-regulation in CPT1 gene expression. FRF treatement markedly reduced the expression of PPAR-γ, FAS, IL-6, and TNF-α compared to those in HFD control, whereas increased the expression level of CPT1. Conclusions: These results suggest that the FRF and its major active constituent, rutin, can be used as effective anti-obesity agents.

Anti-inflammatory effects of Lespedeza Cuneata in vivo and in vitro (야관문(夜關門)의 항염증효과(抗炎症效果))

  • Lee, Hoil;Jung, Ji Yun;Hwangbo, Min;Ku, Sea Kwang;Kim, Young Woo;Jee, Seon Young
    • The Korea Journal of Herbology
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    • v.28 no.4
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    • pp.83-92
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    • 2013
  • Objectives : Lespedeza Cuneata has been used to treat leukorrhea, asthma, stomach pain, diarrhea, acute mastitis, in Korean traditional medicine. According to recent studies, Lespedeza Cuneata has antioxidation, hypoglycemia, cell protective, insulin secretion, whitening, corpora cavernosa smooth muscle relaxation and antimicrobial activities, but it has been rarely conducted to evaluate the immuno-biological activity. The present study was examined to evaluate the anti-inflammatory effects of the Lespedeza Cuneata MeOH extract (LCE) in vivo and in vitro. Methods : In vitro, inflammatory mediators, such as cytokines, nitric oxide and prostaglandin $E_2$ were detected after the addition of LPS with or without LCE in Raw 264.7 macrophage cell line. In vivo, anti-edema effect of LCE was determined in the carrageenan-induced paw edema model in rats. Results : In vitro assay, LCE decreased release of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) via suppression of iNOS and COX-2 expression. LCE inhibited the phosphorylation of $I{\kappa}B$ indicating the suppression of NF-${\kappa}B$ pathway. In vivo assay, LCE significantly inhibited the formation of paw edema induced by carrageenan injection in rats. LCE effectively inhibited increases of hind paw skin thickness and inflammatory cell infilterations. Conclusion : These findings demonstrate that LCE has inhibitory effect on inflammatory mediators in LPS-activated Raw 264.7 cells and on paw edema in carrageenan-stimulated rats, showing the possibility of anti-inflammatory use of Lespedeza Cuneata.