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Altered Renal Sodium Transporter Expression in an Animal Model of Type 2 Diabetes Mellitus
주권욱,Jay Wook Lee,Un Sil Jeon,임춘수,Jin Suk Han,Mark A. Knepper,나기영,오윤규 대한의학회 2007 Journal of Korean medical science Vol.22 No.6
Hemodynamic factors play an important role in the development and/or progression of diabetic nephropathy. We hypothesized that renal sodium transporter dysregulation might contribute to the hemodynamic alterations in diabetic nephropathy. Otsuka Long Evans Tokushima Fatty (OLETF) rats were used as an animal model for type 2 diabetes. Long Evans Tokushima (LETO) rats were used as controls. Renal sodium transporter regulation was investigated by semiquantitative immunoblotting and immunohistochemistry of the kidneys of 40-week-old animals. The mean serum glucose level in OLETF rats was increased to 235±25 mg/dL at 25 weeks, and the hyperglycemia continued up to the end of 40 weeks. Urine protein/ creatinine ratios were 10 times higher in OLETF rats than in LETO rats. At 40th week, the abundance of the epithelial sodium channel (ENaC) -subunit was increased in OLETF rats, but the abundance of the ENaC -subunit was decreased. No significant differences were observed in the ENaC -subunit or other major sodium transporters. Immunohistochemistry for the ENaC -subunit showed increased immunoreactivity in OLETF rats, whereas the ENaC -subunit showed reduced immunoreactivity in these rats. In OLETF rats, ENaC -subunit upregulation and ENaC -subunit downregulation after the development of diabetic nephropathy may reflect an abnormal sodium balance.
주권욱,전은실,오윤규,김근호,한진석,김성권,이정상 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.2
배 경 : 옥시토신은 바소프레신과 매우 유사한 구조의 호르몬으로서, 과거부터 항이뇨 효과가 있을 것으로 생각하였으나, 최근에야 체외실험을 통하여 옥시토신의 항이뇨 작용이 증명되었다. 인체에서도 옥시토신이 항이뇨 호르몬으로 작용할 가능성이 있지만 아직 분명하지 않다. 저자들은 정상인에게 옥시토신 또는 desmopressin(dDAVP)을 투여하여 인체에서 옥시토신의 항이뇨 효과를 직접적으로 검증하고자 하였다. 방 법: 신기능 장애의 증거가 없는 건강한 성인 남자 10명을 대상으로 기저상태와 옥시토신(20 mU/hour로 정주) 또는 dDAVP(2 μg을 피하 주사)를 투여한 후 2시간 동안 수집한 요에서 요량, 요 삼투질농도, 자유수분 청소율 등을 측정하였고, 요 전해질 배설의 변화를 함께 관찰하였다. 결 과 : 혈청 전해질이나 삼투질농도는 옥시토신 또는 dDAVP 투여 후에 기저상태에 비해 유의한 변화가 없었다. 2시간 요량은 기저상태 446±75 mL로부터, dDAVP 투여 후 92±9 mL로 감소하였고(p<0.05), 옥시토신 투여 후에는 289±53 mL로 변화하였다. 요 삼투질농도는 기저상태 223±25.0 mOsm/kg에서, dDAVP 투여 후 936±34 mOsm/kg 및 옥시토신 투여 후427±63 mOsm/kg로 모두 증가하였다(p<0.05). 자유수분 청소율은 기저상태 110±51 mL/2hour로부터, dDAVP 투여 후 -218±28 mL/2 hour, 옥시토신 투여 후 -57±51 mL/2 hour로 각각 감소하였다(p<0.05). 요나트륨분획배설율(FENa)을 포함한 다른 요 전해질 배설의 유의한 변화는 없었다. 결 론 : 옥시토신이 정상 성인 남자에서 요 삼투질농도의 증가 및 자유수분 청소율의 저하를유발함을 확인하였으며, 이는 옥시토신이 인체에서도 항이뇨 작용이 있음을 시사하는 결과이다. 그러나 생리적인 농도에서 옥시토신이 어떤 역할을 할 것인가와 그 작용기전은 앞으로 규명되어야 할 과제이다. Background : The antidiuretic action of oxytocin in human has been controversial. To investigate whether oxytocin directly acts on water balance in human, we evaluated the parameters of urinary concentration in response to administration of oxytocin in ten healthy male volunteers. Methods : Oxytocin was infused intravenously at a rate of 20 mU/hour for 2.5 hours and urine was collected during the last 2 hours of oxytocin infusion. Changes in urine volume, urine osmolality, excretions of urine electrolytes and free water clearance after the administrartion of oxytocin were compared with the baseline data. Results : The changes in the levels of serum electrolytes and osmolality after the administration of oxytocin were not significant compared with the baseline data. The volume of 2 hours' urine were 446±75 mL and 289±53 mL in the basal state and after the administration of oxytocin, respectively. The urine osmolality was increased significantly by the infusion of oxytocin(427±63 mOsm/kg) compared with that in the basal state(223±25 mOsm/kg)(p< 0.05). The free water clearance was 110±51 mL/2 hours in the basal state and decreased significantly to -57±51 mL/2 hours(p<0.05). Conclusion : We conclude that administration of oxytocin to normal men enhances urinary concentration, evidenced by increased urinary osmolality and decreased free water clearance. In human, oxytocin may play an important role in the regulation of renal water excretion as an antidiuretic hormone. (Korean J Nephrol 2002;21(2):251-258)