Rebsomen L, Pitel S, Boubred F, Buffat C, Feuerstein J M, Raccah D, Vague P, Tsimaratos M
UPRES EA 21-93, Laboratoire de diabétologie, Faculté de Médecine de Marseille, Université de la Méditerranée, 13385 Marseille Cedex 05.
Diabetes Metab. 2006 Jun;32(3):223-8. doi: 10.1016/s1262-3636(07)70272-0.
Recent experimental and clinical data suggest that C-peptide replacement during type 1 diabetes exerts beneficial effects on diabetic nephropathy. The aim of this study was to determine if physiological C-peptide administration in replacement dose during 28 days had beneficial effects on metabolic status and renal functions in type-1 diabetic rats.
Four groups of rats were investigated: a non diabetic group treated with buffer (C group, n=6), three streptozotocin diabetic-induced groups treated with either buffer (D group, n=6), insulin (D-I group, n=6) or rat homologous C-peptide (D-C group, n=6). Weight gain was measured every week. All animals were housed in metabolic cages on day 28 for assessment of metabolic data. Blood and urine samples were collected to allow measurement of plasmatic osmolality, C-peptide concentration, sodium, and glucose losses and proteinuria. Glomerular filtration rate (GFR) was determined by creatinine clearance.
All streptozotocin-treated animals were diabetic. Glycaemic control (mg/dl), was markedly improved in D-I (133+/-65) when compared with either D (547+/-49, P<0.05) or D-C (520+/-48, P<0.05) groups. Conversely, weight gain during the study, was improved in D-I and D-C as compared with D animals (135+/-13 and 41+/-18 vs 18+/-21 respectively), despite different glycaemic control. Diabetes-induced glomerular hyperfiltration (ml/min/kg), urinary protein leakage (g/kg/day), and Na urinary losses (mmol/100 g/day) respectively, were significantly (P<0.05) reduced in D-C (3.95+/-0.6; 0.08+/-0.06; 1.5+/-0.9) in comparison with D (4.95+/-0.8; 0.18+/-0.16; 3.7+/-2.1) and D-I (5+/-0.9; 0.19+/-0.11; 2.7+/-0.8) animals. Plasmatic osmolality was significantly increased in D group whereas there were no differences between C group and D-C group. Food and water intakes, urinary volume as well as urinary glucose losses were not significantly different between D-C and D groups.
C-peptide administration in replacement dose to streptozotocin diabetic rats induces weight gain regardless hyperglycaemia or glycosuria. Diabetic animals supplemented with C-peptide exhibit better renal function resulting in reduced urinary sodium waste and protein excretion together with reduction of the diabetes-induced glomerular hyperfiltration.
近期的实验和临床数据表明，1型糖尿病期间进行C肽替代治疗对糖尿病肾病具有有益作用。本研究的目的是确定在28天内给予生理替代剂量的C肽是否对1型糖尿病大鼠的代谢状态和肾功能有有益影响。
研究了四组大鼠：一组用缓冲液治疗的非糖尿病组（C组，n = 6），三组用链脲佐菌素诱导糖尿病的组，分别用缓冲液（D组，n = 6）、胰岛素（D - I组，n = 6）或大鼠同源C肽（D - C组，n = 6）治疗。每周测量体重增加情况。在第28天，所有动物被安置在代谢笼中以评估代谢数据。采集血液和尿液样本以测量血浆渗透压、C肽浓度、钠、葡萄糖流失和蛋白尿。通过肌酐清除率测定肾小球滤过率（GFR）。
所有经链脲佐菌素治疗的动物均患有糖尿病。与D组（547±49，P < 0.05）或D - C组（520±48，P < 0.05）相比，D - I组（133±65）的血糖控制（mg/dl）明显改善。相反，尽管血糖控制不同，但与D组动物相比，D - I组和D - C组在研究期间的体重增加有所改善（分别为135±13和41±18 vs 18±21）。与D组（4.95±0.8；0.18±0.16；3.7±2.1）和D - I组（5±0.9；0.19±0.11；2.7±0.8）相比，D - C组（3.95±0.6；0.08±0.06；1.5±0.9）的糖尿病诱导的肾小球高滤过（ml/min/kg）、尿蛋白漏出（g/kg/天）和尿钠流失（mmol/100 g/天）分别显著降低（P < 0.05）。D组的血浆渗透压显著升高，而C组和D - C组之间无差异。D - C组和D组之间的食物和水摄入量、尿量以及尿葡萄糖流失无显著差异。
给链脲佐菌素诱导的糖尿病大鼠给予替代剂量的C肽可诱导体重增加，无论是否存在高血糖或糖尿。补充C肽的糖尿病动物表现出更好的肾功能，导致尿钠排泄减少和蛋白质排泄减少，同时糖尿病诱导的肾小球高滤过也降低。
