Mak R H, Mehls O
Department of Pediatrics, Stanford University School of Medicine, California 94305-5119, USA.
Am J Physiol. 1996 Aug;271(2 Pt 2):F440-5. doi: 10.1152/ajprenal.1996.271.2.F440.
Insulin resistance is common in acute renal failure (ARF). Insulin-like growth factor (IGF)-I has insulin-like actions. The present study was undertaken to determine whether effects of IGF-I on glucose transport are maintained in rats with ARF and to compare these actions of IGF-I with those of insulin. ARF was induced in male Sprague-Dawley rats by bilateral ureteric ligation, and vascular catheters were inserted at the same time in all animals. Sham-operated controls were pair fed, and metabolic studies were performed 48 h later. ARF rats had higher serum creatinine (1.3 +/- 0.2 mg/dl vs. 0.3 +/- 0.1), lower arterial pH (7.15 +/- 0.03 vs. 7.35 +/- 0.02), and higher fasting serum glucose (150 +/- 13 vs. 123 +/- 12 mg/dl) compared with control rats (P < 0.001 in all cases). The hypoglycemic effects of insulin and IGF-I were compared using euglycemic clamps. In control rats, rates of total body glucose uptake were not different during euglycemic insulin clamps at 2 mU.kg-1.min-1 and euglycemic IGF-I clamps at 5 micrograms.kg-1.min-1. In rats with ARF, total body glucose uptake during euglycemic insulin clamps at 2 mU.kg-1.min-1 was significantly reduced (6.5 +/- 0.5 mg.kg-1.min-1) compared with controls (10.5 +/- 1.5 mg.kg-1.min-1, P < 0.01). In contrast, total body glucose uptake during euglycemic IGF-I clamps at 5 micrograms.kg-1.min-1 in ARF rats (10.1 +/- 1.2 mg.kg-1.min-1) was not different from the corresponding value in control animals (10.3 +/- 1.3 mg.kg-1.min-1). Hepatic glucose production was suppressed by insulin equally but not suppressed by IGF-I in both groups. In a second experiment, ARF was induced by bilateral renal ischemia. The following groups of animals were studied: ARF + NaCl, ARF + NaHCO3, and control + NaCl. Insulin and IGF-I clamps were performed as above. Correction of acidosis partially corrected insulin resistance but did not affect IGF-I sensitivity. Thus the capacity of IGF-I infusion to stimulate glucose uptake is maintained in ARF rats, which are insulin resistant.
胰岛素抵抗在急性肾衰竭（ARF）中很常见。胰岛素样生长因子（IGF）-I具有胰岛素样作用。本研究旨在确定IGF-I对葡萄糖转运的作用在ARF大鼠中是否得以维持，并将IGF-I的这些作用与胰岛素的作用进行比较。通过双侧输尿管结扎诱导雄性Sprague-Dawley大鼠发生ARF，同时在所有动物身上插入血管导管。对假手术对照组进行配对喂养，并在48小时后进行代谢研究。与对照大鼠相比，ARF大鼠的血清肌酐更高（1.3±0.2mg/dl对0.3±0.1），动脉pH更低（7.15±0.03对7.35±0.02）以及空腹血清葡萄糖更高（150±13对123±12mg/dl）（所有情况P<0.001）。使用正常血糖钳夹法比较胰岛素和IGF-I的降血糖作用。在对照大鼠中，在2mU·kg-1·min-1的正常血糖胰岛素钳夹和5μg·kg-1·min-1的正常血糖IGF-I钳夹期间，全身葡萄糖摄取率没有差异。在ARF大鼠中，与对照组（10.5±1.5mg·kg-1·min-1）相比，在2mU·kg-1·min-1的正常血糖胰岛素钳夹期间全身葡萄糖摄取显著降低（6.5±0.5mg·kg-1·min-1，P<0.01）。相反，在ARF大鼠中5μg·kg-1·min-1的正常血糖IGF-I钳夹期间的全身葡萄糖摄取（10.1±1.2mg·kg-1·min-1）与对照动物的相应值（10.3±1.3mg·kg-1·min-1）没有差异。两组中胰岛素均能同等程度抑制肝葡萄糖生成，但IGF-I不能抑制。在第二个实验中，通过双侧肾脏缺血诱导ARF。研究了以下几组动物：ARF+NaCl、ARF+NaHCO3和对照+NaCl。如上述进行胰岛素和IGF-I钳夹。酸中毒的纠正部分纠正了胰岛素抵抗，但不影响IGF-I敏感性。因此，在胰岛素抵抗的ARF大鼠中，输注IGF-I刺激葡萄糖摄取的能力得以维持。
