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      KCI등재 SCOPUS SCIE

      OLETF 쥐에서 메트폴민이 음경 Nitric Oxide Synthase 발현에 미치는 영향 = Effects of Metformin on Penile Expression of Nitric Oxide Synthase in OLETF Rats

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      https://www.riss.kr/link?id=A104591735

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      다국어 초록 (Multilingual Abstract)

      Purpose: It is well known that metformin, an oral biguanide insulin- sensitizing agent, targets AMP-activated protein kinase (AMPK), which activates endothelial nitric oxide synthase (eNOS), which may be associated with erectile dysfunction. The aim o...

      Purpose: It is well known that metformin, an oral biguanide insulin- sensitizing agent, targets AMP-activated protein kinase (AMPK), which activates endothelial nitric oxide synthase (eNOS), which may be associated with erectile dysfunction. The aim of this study was to evaluate whether metformin activates eNOS in the penile tissue of a genetically obese rat model.
      Materials and Methods: We measured phospho-eNOS levels and eNOS expression in the penile tissue of Otsuka Long Evans Tokushima Fatty (OLETF) rats after 3 days of treatment with metformin (150 or 300 mg) to evaluate whether metformin activates eNOS in the penile tissue of this genetically obese rat model. Seven-month-old OLETF rats were used, and eNOS expression was analyzed by real-time polymerase chain reaction (PCR). The experimental groups were compared with use of the Kruskal- Wallis or Mann-Whitney test.
      Results: Seven-month-old OLETF rats had severe visceral fat deposition and elevated serum leptin concentrations. eNOS expression analyzed by real-time PCR was lower in the penile tissue of OLETF rats than in Long Evans Tokushima Otsuka (LETO) rats. Short-term treatment with metformin did not change visceral fat mass or serum leptin levels. However, metformin treatment increased eNOS mRNA expression in the penile tissue as determined by real-time PCR. The levels of phospho-eNOS and phospho-AMPK (pAMPK) in penile tissue revealed a dose-dependent tendency to increase with metformin treatment; however, there was no statistical difference by Kruskal-Wallis test among the experimental groups. The pAMPK level was dose-dependently elevated in the soleus by metformin treatment. There was no significant change in pSTAT3 by metformin treatment in the soleus.
      Conclusions: Metformin activates eNOS mRNA expression in the penile tissue of OLETF rats. Further study on the relation between erectile function and eNOS levels is needed for clinical application.

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      참고문헌 (Reference)

      1 박부경, "흰쥐에서 노화에 따른 음경해면체의 Nitric Oxide Synthase Isoforms 및 Endothelin-1 활성변화" 대한비뇨기과학회 46 (46): 1213-1220, 2005

      2 Choi YD, "The effect of testosterone on nitric oxide synthase in the penis of the rabbit" 40 : 106-112, 1999

      3 Hawley SA, "The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism" 51 : 2420-2425, 2002

      4 Fryer LG, "The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways" 277 : 25226-25232, 2002

      5 Hardie DG, "The AMP-activated protein kinase-fuel gauge of the mammalian cells?" 246 : 259-273, 1997

      6 Chomczynski P, "Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction" 162 : 156-159, 1987

      7 Zhou G, "Role of AMP-activated kinase in mechanism of metformin action" 108 : 1167-1174, 2001

      8 Hambrecht R, "Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase" 107 : 3152-3158, 2003

      9 Knispel HH, "Nitric oxide mediates neurogenic relaxation induced in rabbit cavernous smooth muscle by electric field stimulation" 40 : 471-476, 1992

      10 Kim YW, "Metformin restores the penile expression of nitric oxide synthase in high-fat-fed obese rats" 28 : 555-560, 2007

      1 박부경, "흰쥐에서 노화에 따른 음경해면체의 Nitric Oxide Synthase Isoforms 및 Endothelin-1 활성변화" 대한비뇨기과학회 46 (46): 1213-1220, 2005

      2 Choi YD, "The effect of testosterone on nitric oxide synthase in the penis of the rabbit" 40 : 106-112, 1999

      3 Hawley SA, "The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism" 51 : 2420-2425, 2002

      4 Fryer LG, "The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways" 277 : 25226-25232, 2002

      5 Hardie DG, "The AMP-activated protein kinase-fuel gauge of the mammalian cells?" 246 : 259-273, 1997

      6 Chomczynski P, "Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction" 162 : 156-159, 1987

      7 Zhou G, "Role of AMP-activated kinase in mechanism of metformin action" 108 : 1167-1174, 2001

      8 Hambrecht R, "Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase" 107 : 3152-3158, 2003

      9 Knispel HH, "Nitric oxide mediates neurogenic relaxation induced in rabbit cavernous smooth muscle by electric field stimulation" 40 : 471-476, 1992

      10 Kim YW, "Metformin restores the penile expression of nitric oxide synthase in high-fat-fed obese rats" 28 : 555-560, 2007

      11 Borst SE, "Metformin restores responses to insulin but not to growth hormone in Sprague-Dawley rats" 291 : 722-726, 2002

      12 Kim YW, "Metformin restores leptin sensitivity in high-fat-fed obese rats with leptin resistance" 55 : 716-724, 2006

      13 Minokoshi Y, "Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase" 415 : 339-343, 2002

      14 Liu Y, "High-fat diet feeding impairs both the expression and activity of AMPKa in rats' skeletal muscle" 339 : 707-707, 2006

      15 Andersson KE, "Erectile physiological and pathophysiological pathways involved in erectile dysfunction" 170 : S6-S14, 2003

      16 Kumar VB, "Effect of metformin on nitric oxide synthase in genetically obese (ob/ob) mice" 69 : 2789-2799, 2001

      17 Morrow VA, "Direct activation of AMP-activated protein kinase stimulates nitric-oxide synthesis in human aortic endothelial cells" 278 : 31629-31639, 2003

      18 Moon KH, "Correlation of neuronal nitric oxide synthase with penile erection in diabetic rats" 38 : 575-584, 1997

      19 Kay JP, "Beneficial effects of metformin in normoglycemic morbidly obese adolescents" 50 : 1457-1461, 2001

      20 Covasa M, "Attenuated satiation response to intestinal nutrients in rats that do not express CCK-A receptors" 22 : 1339-1348, 2001

      21 Lee WJ, "Alpha-lipoic acid prevents endothelial dysfunction in obese rats via activation of AMP-activated protein kinase" 25 : 2488-2494, 2005

      22 Davis BJ, "Activation of the AMP- activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthesis" 55 : 496-505, 2006

      23 Fryer LG, "Activation of glucose transport by AMP-activated protein kinase via stimulation of nitric oxide synthase" 49 : 1978-1985, 2000

      24 Andersson U, "AMP-activated protein kinase plays a role in the control of food intake" 279 : 12005-12008, 2004

      25 Roberts CK, "A high-fat, refined-carbohydrate diet induces endothelial dysfunction and oxidant/antioxidant imbalance and depresses NOS protein expression" 98 : 203-210, 2005

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      연월일 이력구분 이력상세 등재구분
      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
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      2016-03-04 학술지명변경 외국어명 : 미등록 -> Investigative and Clinical Urology KCI등재
      2016-01-15 학술지명변경 한글명 : Korean Journal of Urology -> Investigative and Clinical Urology KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-02-21 학술지명변경 한글명 : 대한비뇨기과학회지 -> Korean Journal of Urology
      외국어명 : The Korean Journal of Urology -> 미등록
      KCI등재
      2009-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2007-01-01 평가 등재학술지 유지 (등재유지) KCI등재
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      2002-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.14 0.14 0.13
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.13 0.12 0.314 0.23
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