GLOMERULAR HEMODYNAMIC-ALTERATIONS DURING ACUTE HYPERINSULINEMIA IN NORMAL AND DIABETIC RATS
GLOMERULAR HEMODYNAMIC-ALTERATIONS DURING ACUTE HYPERINSULINEMIA IN NORMAL AND DIABETIC RATS
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DOI：
10.1038/ki.1992.400
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发表时间：
1992-11-01
影响因子：
19.6
通讯作者：
BLANTZ, RC
中科院分区：
文献类型：
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作者：
TUCKER, BJ;ANDERSON, CM;BLANTZ, RC
胰岛素依赖型糖尿病的治疗总是需要外源性胰岛素来控制血糖。胰岛素治疗独立于其他与胰岛素依赖型糖尿病相关的因素，可能会引起影响肾小球功能的变化。由于胰岛素依赖型糖尿病患者体内胰岛素的外源性输送先于门静脉进入体循环，因此其血浆胰岛素水平通常高于非糖尿病患者。高胰岛素血症对肾小球血流动力学的具体影响以前还没有被研究过。在给予链脲佐菌素65 mg/kg体重后7~10天，对对照组(非糖尿病大鼠)、未治疗糖尿病大鼠和胰岛素治疗糖尿病大鼠进行微针刺实验。在进行第一阶段的微穿刺术后，静注5U的普通胰岛素(悍马-R)，并将葡萄糖钳制在正常血糖水平(80~120 mg/dl)。非糖尿病对照组血糖浓度为99+/-6 mg/dl。在对照组大鼠中，胰岛素输注和葡萄糖钳夹可增加肾单位滤过率，这是由于传入和传出小动脉阻力降低(传入大于传出)，导致血浆流量增加和肾小球静水压力梯度增加。然而，胰岛素输注和葡萄糖钳夹对未治疗和胰岛素治疗的糖尿病大鼠均产生相反的作用，导致传入小动脉血管收缩，导致血浆流量、肾小球静水压力梯度和肾单位滤过率下降。血栓素A2(TX)合成酶抑制可部分降低糖尿病大鼠急性胰岛素注射所致的血管收缩反应，阻止肾单位滤过率的下降。然而，在糖尿病大鼠和对照组大鼠中，Tx抑制的作用都降低了胰岛素输注前的肾单位滤过率，这可能表明其他神经体液因子参与了Tx抑制的增强。
Treatment of insulin dependent diabetes invariably requires exogenous insulin to control blood glucose. Insulin treatment, independent of other factors associated with insulin dependent diabetes, may induce changes that affect glomerular function. Due to exogenous delivery of insulin in insulin dependent diabetes entering systemic circulation prior to the portal vein, plasma levels of insulin are often in excess of that observed in non-diabetics. The specific effects of hyperinsulinemia on glomerular hemodynamics have not been previously examined. Micropuncture studies were performed in control (non-diabetic), untreated diabetic and insulin-treated diabetic rats 7 to 10 days after administration of 65 mg/kg body weight streptozotocin. After the first period micropuncture measurements were obtained, 5 U of regular insulin (Humulin-R) was infused i.v., and glucose clamped at euglycemic values (80 to 120 mg/dl). Blood glucose concentration in non-diabetic controls was 99 +/- 6 mg/dl. In control rats, insulin infusion and glucose clamp increased nephron filtration rate due to decreases in both afferent and efferent arteriolar resistance (afferent greater than efferent) resulting in increased plasma flow and increased glomerular hydrostatic pressure gradient. However, insulin infusion and glucose clamp produced the opposite effect in both untreated and insulin-treated diabetic rats with afferent arteriolar vasoconstriction resulting in decreases in plasma flow, glomerular hydrostatic pressure gradient and nephron filtration rate. Thromboxane A2 (TX) synthetase inhibition partially decreased the vasoconstrictive response due to acute insulin infusion in diabetic rats preventing the decrease in nephron filtration rate. However, the action of TX inhibition decreased nephron filtration rate prior to insulin infusion in both diabetic and control rats, which may indicate participation of other neuro-humoral agents potentiated by TX inhibition.