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The Difference of Efficacy for Oral Hypoglysemic Pharmacotherapy Based on Sasang Constitutional Medicine Among Type II Diabetes Mellitus Patients in Korea (제 2형 당뇨병 환자에서 사상체질에 따른 경구 혈당강하요법의 치료 반응성 및 사용 패턴 평가)

  • Kim, Ji Yeon;Lee, Myung Koo;Kim, Jung Tae;Lim, Sung Cil
    • YAKHAK HOEJI
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    • v.58 no.1
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    • pp.71-79
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    • 2014
  • Although Korean patients with type 2 diabetes mellitus (T2DM) are generally treated by western medicine, many of them strongly believe in the traditional oriental Sasang constitutional classification and depend on it for food, health supplements, and oriental medicines decision making. Sasang constitutional classification is a part of traditional Korean medicine that divides people into four constitutional types (Tae-Yang: TY, Tae-Eum: TE, So-Yang: SY, and So-Eum: SE), which differ in inherited characteristics such as appearance, personality traits, susceptibility to diseases, and drug responses. It is recommended for T2DM patients to control their blood glucose very well from early stages with drugs and diet. However, many T2DM patients respond differently to their drugs, even though they receive the same medicine. Therefore, the present study investigated whether Sasang constitutional type can explain the therapeutic differences between oral hypoglycemic agents (OHAs) therapy (mono, dual and triple drug therapy). Patients of 618 with T2DM diagnosis and Sasang constitutional type known who received both western and oriental medicine treatment in a hospital between April 2006 and April 2013 retrospectively studied. HbA1c (%) and blood glucose (mg/dl) levels before OHAs therapy and 3 month after were collected for metformin (MET) or sulfonylurea (SU) monotherapy, MET+SU dual therapy, MET+except SU (where was either alpha-glucosidase inhibitor, dipeptidyl peptidase-4 inhibitor, meglitinide or thiazolidinedione) dual therapy, and triple therapy, according to Sasang constitutional type. For statistical analysis, ANOVA was used and paired t-test by SPSS 19.0 where P values less than 0.05 were considered statistically significant. Pattern was similar levels of HbA1c and blood glucose and which was decreased in order of mono, MET+SU dual, MET+except SU dual and triple therapy. In all patients comparison, for the So-yang (SY) constitutional type, either monotherapy was less effective; for Te-eum (TE) type, MET+SU dual therapy was less effective while MET+except SU dual therapy was more effective and the triple therapy was less effective; and for So-eum (SE) type, the triple therapy was more effective. For the management of TE type it is recommended to use drugs except SU when dual therapy is needed, restrict triple therapy and consider dual and insulin therapy; for SY type it is recommended to follow current guidelines; and for SE type it is advisable to skip dual therapy and start the triple therapy early. Finally, the therapeutic response to OHAs is different among Korean T2DM patients with different Sasang constitutional types. Taken together, the choice of effective OHAs therapy for each type is necessary in order to minimize the poor control of blood glucose level, the risk of complications, and the costs from a failure of therapy.

The Effects of Bojungikgi-tang on Streptozotocin-induced Diabetic Gastroparesis Rat Model (보중익기탕(補中益氣湯)이 streptozotocin 유발 당뇨병성 위부전마비 백서에 미치는 영향)

  • Kang, Yun-Mi;Kim, Hyo-Jung;Park, Yun-Beom;Jeong, Chan-Mun;Ham, Seong-Ho;Yang, Woong-Mo;An, Hyo-Jin
    • The Korea Journal of Herbology
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    • v.34 no.6
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    • pp.45-55
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    • 2019
  • Objective : Diabetic gastroparesis is a complication that is defined as delayed gastric emptying and upper gastrointestinal symptoms and often occurs in long-standing diabetic patients. Bojungikgi-tang (BJT) is a traditional oriental herbal formula that has long been used for the treatment of digestive disorders. The purpose of this study was to investigate the effects of BJT on streptozotocin (STZ)-induced diabetic gastroparesis rat model. Methods : Sprague-Dawley (SD) male rats (250-270g) were divided into 13 groups including normal group, STZ-induced diabetic control group, BJT diet (7 various concentrations), and insulin-, glibenclamide-, metformin-treated group were used for the experiments for the comparison. Diabetic gastroparesis was induced by intraperitoneal injection of STZ. The water intake, food intake, body weights and fasting blood glucose levels were measured. After 4 weeks the animals were sacrificed and gastrin, leptin, insulin, hemoglobin A1C (HbA1c), lactate, lactate dehydrogenase (LDH), bilirubin, creatinine, albumin and lipid levels were evaluated. Results : Intraperitoneal injection of BJT for 4 weeks resulted in increased levels of gastrin in blood and decreased leptin and lactate concentration in STZ-induced diabetic gastroparesis rat model. BJT did not affect insulin, fasting glucose, HbA1c, and lipid levels in STZ-induced diabetic gastroparesis rat model. Conclusion : These results indicated that BJT would have protect effect on diabetic gastroparesis through the improvement effect of gastric motility and fatigue syndrome in STZ-induced diabetic rats. This study shows that BJT might be effective for treatment of diabetes and its complications such as gastroparesis.

Investigation on the occurrence and fate of micropollutants in domestic wastewater treatment plants based on full-scale monitoring and simple statistical analysis (현장 모니터링과 기초통계분석에 기반한 국내 하수처리장 미량오염물질 발생 및 거동 조사)

  • Chae, Sung Ho;Lim, Seung Ji;Lee, Jiho;Gashaw, Seid Mingizem;Lee, Woongbae;Choi, Sangki;Lee, Yunho;Lee, Woorim;Son, Heejong;Hong, Seok-Won
    • Journal of Korean Society of Water and Wastewater
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    • v.36 no.2
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    • pp.107-119
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    • 2022
  • The frequent detection and occurrence of micropollutants (MPs) in aquatic ecosystems has raised public health concerns worldwide. In this study, the behavior of 50 MPs was investigated in three different domestic wastewater treatment plants (WWTPs). Furthermore, the Kruskal-Wallis test was used to assess the geographical and seasonal variation of MPs in the WWTPs. The results showed that the concentrations of 43 MPs ranged from less than 0.1 to 237.6 ㎍ L-1, while other seven MPs including 17-ethynylestradiol, 17-estradiol, sulfathiazole, sulfamethazine, clofibric acid, simvastatin, and lovastatin were not detected in all WWTPs. Among the detected MPs, the pharmaceuticals such as metformin, acetaminophen, naproxen, and caffeine were prominent with maximum concentrations of 133.4, 237.6, 71.5, and 107.7 ㎍ L-1, respectively. Most perfluorinated compounds and nitrosamines were found at trace levels of 1.2 to 55.3 ng L-1, while the concentration of corrosion inhibitors, preservatives (parabens), and endocrine disruptors ranged from less than 0.1 to 4310.8 ng L-1. Regardless of the type of biological treatment process such as MLE, A2O, and MBR, the majority of pharmaceuticals (except lincomycin, diclofenac, iopromide, and carbamazepine), parabens (except Methyl paraben), and endocrine disruptors were removed by more than 80%. However, the removal efficiencies of certain MPs such as atrazine, DEET, perfluorinated compounds (except PFHxA), nitrosamines, and corrosion inhibitors were relatively low or their concentration even increased after treatment. The results of statistical analysis reveal that there is no significant geographical difference in the removal efficacy of MPs, but there are temporal seasonal variations in all WWTPs.

The Effects of Galgunhwanggumhwangryun-tang on Glucose and Energy Metabolism in C2C12 Myotubes (C2C12 골격근 세포에서 갈근황금황련탕의 당 대사 및 에너지 조절 효과)

  • Jihong Oh;Song-Yi Han;Soo Kyoung Lim;Hojun Kim
    • Journal of Korean Medicine for Obesity Research
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    • v.22 no.2
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    • pp.93-101
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    • 2022
  • Objectives: This study aimed to observe the anti-diabetic effect and underlying mechanisms of Galgunhwanggumhwangryun-tang (GHH; Gegen-Qinlian-decoction) in the C2C12 myotubes. Methods: GHH (1.0 mg/ml) or metformin (0.75 mM) or insulin (100 nM) were treated in C2C12 myotubes after 4 days differentiation. The glucose uptake was assessed by 2-[N-(7-160 nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake by C2C12 cells. The expression of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation AMPK (pAMPK) were measured by western blot. We also evaluated gene expression of glucose transporter type 4 (Slc2a4, formerly known as GLUT4), glucokinase (Gk), carnitine palmitoyltransferase IA (Cpt1a), nuclear respiratory factors 1 (Nrf1), mitochondrial transcription factor A (Tfam), and peroxisome proliferator-activated receptor γ coactivator 1α (Ppargc1a) by quantitative real-time polymerase chain reaction. Results: GHH promoted glucose uptake in C2C12 myotubes. The expression of AMPK protein, which plays an essential role in glucose metabolism, was increased by treatment with GHH. GHH treatment tended to increase gene expression of Slc2a4, Gk, and Nrf1 but was not statistically significant. However, GHH significantly improved Tfam and Ppargc1a gene expression in C2C12 myotubes. Conclusions: In summary, GHH treatment promoted glucose uptake in C2C12 myotubes. We suggest that these effects are associated with increased gene expression involved in mitochondrial biosynthesis and oxidative phosphorylation, such as Tfam and Ppargc1a, and increased expression of AMPK protein.

Korean Treatment Guideline on Pharmacotherapy of Co-existing Symptoms and Antipsychotics-related Side Effects in Patients with Schizophrenia ('2019 한국형 조현병 약물치료 지침서'에 따른 조현병에서 동반증상 및 부작용의 치료)

  • Yun, Je-Yeon;Lee, Jung Suk;Kang, Shi Hyun;Nam, Beomwoo;Lee, Seung Jae;Lee, Seung-Hwan;Choi, Joonho;Kim, Chan-Hyung;Chung, Young-Chul
    • Korean Journal of Schizophrenia Research
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    • v.22 no.2
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    • pp.21-33
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    • 2019
  • Objectives: The current study covers a secondary revision of the guidelines for the pharmacotherapy of schizophrenia issued by the Korean Medication Algorithm for Schizophrenia (KMAP-SCZ) 2001, specifically for co-existing symptoms and antipsychotics-related side-effects in schizophrenia patients. Methods: An expert consensus regarding the strategies of pharmacotherapy for positive symptoms of schizophrenia, co-existing symptoms of schizophrenia, and side-effect of antipsychotics in patients with schizophrenia was retrieved by responses obtained using a 30-item questionnaire. Results: For the co-existing symptoms, agitation could be treated with oral or intramuscular injection of benzodiazepine or antipsychotics; depressive symptoms with atypical antipsychotics and adjunctive use of antidepressant; obsessive-compulsive symptoms with selective serotonin reuptake inhibitors and antipsychotics other than clozapine and olanzapine; negative symptoms with atypical antipsychotics or antidepressants; higher risk of suicide with clozapine; comorbid substance abuse with use of naltrexone or bupropion/varenicline, respectively. For the antipsychotics-related side effects, anticholinergics (extrapyramidal symptom), propranolol and benzodiazepine (akathisia), topiramate or metformin (weight gain), change of antipsychotics to aripiprazole (hyperprolactinemia and prolonged QTc) or clozapine (tardive dyskinesia) could be used. Conclusion: Updated pharmacotherapy strategies for co-existing symptoms and antipsychotics-related side effects in schizophrenia patients as presented in KMAP-SCZ 2019 could help effective clinical decision making of psychiatrists as a preferable option.

Anti-Diabetic Effects of Sprouts in High-Fat Diet and Streptozotocin-Induced Type II Diabetes Mellitus Mice (고지방식이와 STZ 유도 제2형 당뇨 마우스에서 새싹의 항당뇨 효과)

  • Lee, Hyun-Seo;Kang, Hyun Ju;Jeon, In Hwa;Youm, Jung Ho;Jang, Seon Il
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.11
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    • pp.1658-1664
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    • 2014
  • Sprout vegetables containing various types of polyphenols and flavonoids, are known to have anti-inflammatory, antioxidant, cholesterol-lowering, and anti-obesity activities. However, there have been few reports on the anti-diabetic efficacy of sprout vegetables. Here, we investigated the anti-diabetic effects of sprout extract obtained from buckwheat, beet, rape, broccoli, kohlrabi, red young radish, and dachai, in high fat diet (HFD) and streptozotocin (STZ)-induced type II diabetes mellitus mice. The mice were fed a HFD (60% calories as fat) for 8 weeks prior to intraperitoneal injection with STZ (75 mg/kg). The diabetic mice were divided into four groups: standard diet (STD, 10% calories fat), HFD, HFD with sprout extract (SPE) and HFD with metformin (MET). After 4 weeks, body weight gain was much lower in both SPE and MET groups than in HFD group. In contrast, there was no difference experiment groups regarding food intake ratio. The level of fasting blood glucose was significantly lower in the SPE and MET groups compared to the HFD group. Oral glucose tolerance and insulin tolerance in the SPE and MET groups were significantly ameliorated in comparison to the HFD group. The concentrations of serum total cholesterol, triglycerides, and LDL cholesterol in the SPE and MET groups were remarkably reduced in comparison to the HFD group, and HDL cholesterol concentration was higher in the SPE and MET groups than in the HFD group. Glutamate oxaloacetate transaminase and glutamate pyruvate transaminase levels were between SPE and HFD groups. The serum insulin and leptin concentrations were significantly reduced in both the SPE and MET groups compared to the HFD group. Therefore, these results indicate that sprout extract could improve insulin resistance and attenuate blood glucose level in HFD/STZ-induced type II diabetes mellitus mice. We conclude that this study may provide positive insights into sprout extract as a functional food ingredient for treatment of type II diabetes mellitus.

Hypoglycemic and Hypolipidemic Effects of Jerusalem artichoke Composites in Streptozotocin induced Diabetic Rats (명월초, 여주 및 울금을 포함하는 돼지감자 복합물의 streptozotocin 유발 당뇨쥐에서 혈당강하 및 체내 지질개선에 미치는 영향)

  • Hu, Wen-Si;Lee, Soo-Jung;Pyo, Jae-Ho;Kim, Sung-Hee;Sung, Nak-Ju
    • Journal of Life Science
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    • v.28 no.6
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    • pp.671-680
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    • 2018
  • Hypoglycemic and hypolipidemic effects of Jerusalem artichoke composites (JAP) with extracts of G. procumbens (12.5%), M. charantia (12.5%), and C. longa (12.5%) to H. tuberosus concentrate (JA, 50%) were evaluated in streptozotocin (STZ) induced diabetic rats. Rats were divided into seven groups: normal (Normal), diabetic control (Diabetic), group fed G. procumbens extract (0.5 g/kg bw, D-GPE), group fed JAP (0.5 g/kg bw, D-JAP1; 1.5 g/kg bw, D-JAP2), group fed JA (0.5 g/kg bw, D-JA), and group fed Metformin (0.2 g/kg bw, D-MET) as a positive control. The blood glucose levels over 4 weeks were significantly decreased in the D-JAP2 and D-MET groups compared to the other groups after 3 weeks. The serum insulin level was not significant among the groups fed an experimental diet, but the HOMA-IR value was significantly decreased compared to the diabetic control group. AST and ALT activities in the serum were lowest in D-JAP1. Total lipid and triglyceride contents in the serum decreased in the groups fed an experimental diet, and the HDL-C contents of D-GPE, D-JAP1, and D-JAP2 were significantly increased compared to the diabetic control group. Triglyceride contents in the liver tissue were significantly lower in the D-GPE, D-JAP1, and D-JAP2 groups, and hepatic TBARS content was significantly decreased in the D-JAP1 and D-JAP2 groups compared to the diabetic control group. Hepatic antioxidative enzyme levels, such as SOD, catalase, and GSH-Px, were significantly elevated in groups fed an experimental diet compared to the diabetic control group. Therefore, JAP may be more effective than JA in the human body due to its hypoglycemic and hypolipidemic activities.

Anti-diabetic effect and mechanism of Korean red ginseng extract in C57BL/KsJ db/db mice

  • Yuan, Hai-Dan;Shin, Eun-Jung;Chung, Sung-Hyun
    • Proceedings of the Ginseng society Conference
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    • 2007.12a
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    • pp.57-58
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    • 2007
  • Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.

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