Sjöquist M, Huang W, Johansson B L
Department of Physiology, Biomedicum, Uppsala University, Sweden.
Kidney Int. 1998 Sep;54(3):758-64. doi: 10.1046/j.1523-1755.1998.00074.x.
C-peptide has been reported to have biological effects on renal function early in the course of diabetes. This investigation was initiated to elucidate and amplify these findings with respect to protein leakage, hyperfiltration and renal functional reserve in diabetic rats.
Acute effects of 140 minutes i.v. infusion of human C-peptide (0.5 nmol x min(-1) x kg(-1) body wt) on renal function and urinary protein leakage were studied in anesthetized diabetic male rats two weeks after streptozotocin injection without insulin treatment. Streptozotocin-induced diabetic rats were studied with (N = 6) and without C-peptide (N = 11) treatment. The two groups showed a similarly elevated blood glucose concentration during the study. Age-matched normal rats served as controls (N = 5). Glomerular filtration rate (GFR) was measured by inulin clearance in the basal state and during a 60-minute glycine infusion (0.22 mmol x min(-1) x kg(-1) body wt)-resembling a protein load challenge-to test the renal functional reserve in all three groups.
In the basal state, the non-C-peptide-treated diabetic rats displayed increased GFR and increased total protein leakage compared with normal rats. Whereas normal rats responded to glycine infusion with an increase in GFR, no increase occurred in diabetic rats not treated with C-peptide. In diabetic rats given C-peptide, this reduced the initial glomerular hyperfiltration prior to glycine infusion. This indicates a specific effect, since a control peptide with the same amino acid composition as C-peptide, but in a randomized sequence, had no such effect. C-peptide also restored half of the normal renal functional reserve and resulted in 70% lower (P < 0.05) total protein leakage compared with that in rats not given C-peptide.
Thus, short-term infusion of C-peptide had beneficial effects on protein leakage and hyperfiltration and improved the renal functional reserve in rats with experimental diabetes.
据报道，C肽在糖尿病病程早期对肾功能具有生物学效应。本研究旨在阐明并扩展这些关于糖尿病大鼠蛋白质渗漏、超滤和肾功能储备的研究结果。
在链脲佐菌素注射两周后未经胰岛素治疗的麻醉雄性糖尿病大鼠中，研究静脉输注人C肽（0.5 nmol·min⁻¹·kg⁻¹体重）140分钟对肾功能和尿蛋白渗漏的急性影响。对链脲佐菌素诱导的糖尿病大鼠进行C肽治疗（N = 6）和未进行C肽治疗（N = 11）的研究。两组在研究期间血糖浓度均同样升高。年龄匹配的正常大鼠作为对照（N = 5）。通过菊粉清除率在基础状态下以及在60分钟甘氨酸输注（0.22 mmol·min⁻¹·kg⁻¹体重）期间测量肾小球滤过率（GFR），甘氨酸输注类似于蛋白质负荷挑战，以测试所有三组的肾功能储备。
在基础状态下，未接受C肽治疗的糖尿病大鼠与正常大鼠相比，GFR增加且总蛋白渗漏增加。正常大鼠对甘氨酸输注的反应是GFR增加，而未接受C肽治疗的糖尿病大鼠则无增加。在给予C肽的糖尿病大鼠中，这降低了甘氨酸输注前最初的肾小球超滤。这表明存在特异性效应，因为与C肽具有相同氨基酸组成但序列随机的对照肽没有这种效应。C肽还恢复了一半的正常肾功能储备，并且与未给予C肽的大鼠相比，总蛋白渗漏降低了70%（P < 0.05）。
因此，短期输注C肽对实验性糖尿病大鼠的蛋白质渗漏和超滤具有有益作用，并改善了肾功能储备。
