Renal mass reduction increases the response to exogenous insulin independent of acid-base status or plasma insulin levels in rats.
Renal mass reduction increases the response to exogenous insulin independent of acid-base status or plasma insulin levels in rats.
复制标题
肾质量减少增加了大鼠对外源胰岛素的反应，与酸碱状态或血浆胰岛素水平无关。
DOI：
10.1152/ajprenal.00679.2020
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
O'Connor,PaulM
中科院分区：
文献类型：
--
作者：
Mannon,ElinorC;Sartain,ChristinaL;Wilkes,TrevinC;Sun,Jingping;Polichnowski,AaronJ;O'Connor,PaulM
胰岛素敏感性受损可发生在慢性肾病（CKD）患者中。纠正代谢性酸中毒与改善CKD患者的胰岛素敏感性相关，表明代谢性酸中毒可能直接促进胰岛素抵抗。尽管如此，尚未直接研究酸或碱负荷对CKD（残肾）啮齿动物模型中胰岛素敏感性的影响。这些研究可以更好地确定血液pH值和胰岛素敏感性之间的关系。我们假设在残肾大鼠中，酸或碱负荷会促进pH稳态的丧失，从而降低胰岛素敏感性。为了验证这一假设，我们确定了碱（2周）或酸（5-7天）负荷对假手术对照大鼠、2/3肾切除大鼠或5/6肾切除大鼠血浆电解质、酸碱平衡和胰岛素敏感性的影响。5/6肾切除大鼠对胰岛素的反应最大，其次是2/3肾切除大鼠和假手术对照大鼠。我们发现，在饮用水中加入0.1 M碳酸氢钠溶液对胰岛素敏感性没有影响。用0.1 M氯化铵加载酸导致pH值和血浆碳酸氢盐显著降低。然而，酸中毒并没有显着损害胰岛素敏感性。在5/6肾切除的Zucker肥胖大鼠中观察到类似的效果。肾脏质量减少对胰岛素敏感性的影响不能通过胰岛素清除率降低或血浆胰岛素水平升高来解释。我们发现，肾脏重量减少单独增加大鼠对外源性胰岛素的敏感性，并且这不会被酸中毒的发展急性逆转。新&值得注意的是，胰岛素敏感性受损可能发生在慢性肾脏疾病患者中，以前的工作表明代谢性酸中毒可能是根本原因。我们的研究探讨了酸或碱负荷对慢性肾脏疾病啮齿动物模型胰岛素敏感性的影响。我们发现，肾脏质量减少增加了血糖对胰岛素的反应，并且这不会因酸中毒的发展而急性逆转。
Impairments in insulin sensitivity can occur in patients with chronic kidney disease (CKD). Correction of metabolic acidosis has been associated with improved insulin sensitivity in CKD, suggesting that metabolic acidosis may directly promote insulin resistance. Despite this, the effect of acid or alkali loading on insulin sensitivity in a rodent model of CKD (remnant kidney) has not been directly investigated. Such studies could better define the relationship between blood pH and insulin sensitivity. We hypothesized that in remnant kidney rats, acid or alkali loading would promote loss of pH homeostasis and consequently decrease insulin sensitivity. To test this hypothesis, we determined the impact of alkali (2 wk) or acid (5–7 days) loading on plasma electrolytes, acid-base balance, and insulin sensitivity in either sham control rats, 2/3 nephrectomized rats, or 5/6 nephrectomized rats. Rats with 5/6 nephrectomy had the greatest response to insulin followed by rats with 2/3 nephrectomy and sham control rats. We found that treatment with 0.1 M sodium bicarbonate solution in drinking water had no effect on insulin sensitivity. Acid loading with 0.1 M ammonium chloride resulted in significant reductions in pH and plasma bicarbonate. However, acidosis did not significantly impair insulin sensitivity. Similar effects were observed in Zucker obese rats with 5/6 nephrectomy. The effect of renal mass reduction on insulin sensitivity could not be explained by reduced insulin clearance or increased plasma insulin levels. We found that renal mass reduction alone increases sensitivity to exogenous insulin in rats and that this is not acutely reversed by the development of acidosis.NEW & NOTEWORTHYImpairments in insulin sensitivity can occur in patients with chronic kidney disease, and previous work has suggested that metabolic acidosis may be the underlying cause. Our study investigated the effect of acid or alkali loading on insulin sensitivity in a rodent model of chronic kidney disease. We found that renal mass reduction increases the blood glucose response to insulin and that this is not acutely reversed by the development of acidosis.