Experimental diabetic renal growth: role of growth hormone and insulin-like growth factor-I

We have compared the kidneys of two inbred strains of rats (Lewisand Lewis-Dwarf) 7 days after the induction of diabetes mellituswith streptozotocin, in order to examine the influence of aselective growth hormone (GH) deficiency on diabetic renal growthand insulin-like growth factor-I (IGF-I) content of the kidneys.Insulin-like growth factor-I was measured by radioimmunoassayand its distribution within the kidney by immunohistochemicalstaining. We detected a significant increase in both the wetweight (32.9±5.3%, P=0.0085) and dry weight (16.3±6.3%,P=0.046) of the kidneys of diabetic Lewis rats but dwarf rats,selectively deficient in GH, did not show a significant increasein either parameter. Extractable IGF-I increased within thekidneys of diabetic rats of both strains but to a lesser extentin the dwarf rats (+105±28% and +65±21% respectively,P<0.0l). In diabetic Lewis rats a positive correlation wasnoted between the severity of glycaemia and kidney IGF-I content(r=0.604, P<0.05) but no such correlation was noted in dwarfrats. Insulin-like growth factor-I immunostaining increased in diabeticrats of both strains, mainly within cells of the thick ascendinglimb of the loop of Henle including damaged and vacuolated cells.However, morphometric analysis of the staining showed that itwas significantly less widespread in the diabetic dwarf rats(P=0.026). We conclude that growth hormone deficiency bluntsexperimental diabetic renal growth and restricts the increasein the kidney IGF-I content. These findings raise further questionsconcerning the contribution of GH and IGF-I to the early stagesof experimental diabetic renal disease.     

重组人生长激素对肝硬化大鼠肝部分切除术后生长激素/胰岛素样生长因子-1轴的影响

目的探讨rhGH对肝硬化大鼠肝部分切除术后GH/IGF-1轴的影响。方法6只正常大鼠作为正常对照组,24只肝硬化大鼠随机分为术前组6只,肝部分切除术后1d组6只,肝部分切除后行PN5d组6只,肝部分切除术后行rhGH+PN5d组6只。测大鼠肝功能、血糖及血清GH、IGF-1、IGFBP-3水平,用RT-PCR法检测肝ALBmRNA、IGF-1mRNA、IGFBP-3mRNA的表达。肝组织行Ki67免疫组化染色。结果与PN组比较,rhGH+PN组血清ALP显著下降(P<0·05),血清ALB显著升高(P<0·05),血糖显著升高(P<0·05),血清GH、IGF-1、IGFBP-3水平显著升高(P<0·05),肝ALBmRNA、IGF-1mRNA表达水平显著升高(P<0·05),肝Ki67指数也显著升高(P<0·05)。且血清GH水平与血糖呈正相关(P<0·05),血清IGF-1、IGFBP-3水平与血清AST、ALT、ALP呈负相关(P<0·05),与血清ALB量正相关(P<0·05)。结论rhGH可以改善肝硬化大鼠肝部分切除术后GH/IGF-1轴,血清IGF-1、IGFBP-3水平有助于判断营养支持的效果。     

胰岛素样生长因子结合蛋白-2水平与肝癌关系的研究

目的探讨血清胰岛素样生长因子结合蛋白-2(IGFBP-2)水平与肝细胞癌的关系及其在肝癌的诊断、治疗中潜在价值。方法采用酶联免疫吸附试验ELISA法测定肝细胞癌组(54例)血清IGFBP-2、IGFBP-3、AFP、IGF-1、IGF-2、GH水平与肝硬化组(20例)和健康对照组(32例)结果对照比较。结果肝细胞癌组血清IGFBP-2水平明显高于肝硬化组和健康对照组(t=4.63,P<0.05,t=3.73,P<0.01),肝硬化组和健康对照组比较差异无统计学意义。肝癌切除术后4周IGFBP-2水平明显下降,与术前相比差异有统计学意义(t=3.52,P<0.05)。肝细胞癌组GH、IGF-1、IGF-2、IGFBP-3水平与肝硬化组对比差异无统计学意义。相关性分析显示肝细胞癌组IGFBP-2与AFP水平呈正相关(r=0.51,P<0.05),与GH、IGF-1、IGF-2、IGFBP-3无相关性。结论肝细胞癌患者IGFBP-2水平的异常增高可能与肝癌细胞合成释放增加有关。与AFP结合使用血清IGFBP-2检测可成为肝癌筛查、监测的有效手段。     

Haemodialysis with the biocompatible high permeability AN-69 membrane does not alter plasma insulin-like growth factor-I and insulin-like growth factor binding protein-3.

BACKGROUND: Insulin-like growth factor-I (IGF-I) bioactivity has been reported to be decreased in maintenance haemodialysis patients and this may affect their nutritional status. Clearances of IGF-I and its binding proteins (IGFBPs) during haemodialysis sessions using a high permeability biocompatible membrane are unknown. METHODS: Five well nourished, non-diabetic adult patients were studied during one 4-h morning haemodialysis treatment using the high permeability biocompatible AN-69 dialyser. Blood was collected at the arterial and venous ports of the dialyser at 0, 1, 2 and 4 h of dialysis for haematocrit, plasma IGF-I, IGFBP-3 and insulin measurements. IGF-I, IGFBP-3 and insulin concentrations were adjusted for haemoconcentration before comparisons were made. RESULTS: At the beginning of the dialysis session, plasma IGF-I, IGFBP-3 and insulin levels were within the normal range (297 +/- 47 ng/ml (mean+/-SEM), 4.3 +/- 0.6 microg/ml and 11.8 +/- 3.4 microIU/ml, respectively). During the session, insulin tended to be cleared through the dialyser, whereas plasma IGF-I and IGFBP-3 values did not vary significantly. CONCLUSION: Dialysis with the high permeability AN69 membrane did not alter the main blood compounds of the IGF system in well nourished chronic haemodialysis patients, and it is unlikely that the malnutrition frequently observed in such patients would result from alterations of the IGF system during haemodialysis.     

Comparison between somatostatin analogues and ACE inhibitor in the NOD mouse model of diabetic kidney disease.

BACKGROUND: The growth hormone (GH)-insulin-like growth factor (IGF)-SST (SST) axis is involved in diabetic nephropathy (DN). We have recently shown a beneficial effect on diabetic kidney disease markers by the use of a novel somatostatin (SST) analogue (PTR-3173) (S). The purpose of this study is to compare the effects of S with a previously used SST analogue (octreotide) and an ACE inhibitor (ACEi), a standard of care in DN. METHODS: Non-obese diabetic mice (a model of type I diabetes) were treated with either S (DS), octreotide (DO), enalapril (DA), or PTR-3173 and enalapril (DAS group) for 3 weeks. RESULTS: Diabetic renal hypertrophy was blunted in the DS and DO groups only. Serum GH and IGF-I were markedly increased and decreased, respectively, in the D group, a change significantly blunted in DO and DS. Diabetic hyperfitration and albuminuria were blunted in all the four treated diabetic groups. The marked deposition of type IV collagen and PAS material were mildly decreased in DA, but more markedly reduced in DS as well as DO. Diabetic renal laminin accumulation was suppressed in all treated animal groups. No synergistic effect was observed for any parameter in the combination group DAS. CONCLUSION: SST analogues exert beneficial effects in most parameters of diabetic kidney disease to the same extent as the ACEi. Enalapril treatment had no effect on renal hypertrophy and did not cause a significant decrease in mesangial type IV collagen deposition. A synergistic effect of combined SST-ACEi therapy could not be shown in this study.     

Serum growth factors and growth indices pre- and post-pediatric intestinal transplantation

Background/purpose

Although intestinal transplantation (ITx) has succeeded in liberating children with intestinal failure from total parenteral nutrition (TPN), positive growth has yet to be achieved in the majority of patients. This investigation aims to evaluate levels of serum growth factors as they relate to growth parameters and nutritional outcomes.

Methods

Serum measures of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) that had been obtained before and after transplantation were reviewed (with Institutional Review Board approval) in a subset of pediatric ITx recipients. Z-scores for weight and height were calculated at transplant and biannually thereafter for 2 years.

Results

Five children received a small bowel/liver transplant between August 1996 and March 2000 (median age, 1.3 years). Before transplantation, levels of IGF-1 and IGFBP-3 were low in 60% and 67% of patients, respectively. Posttransplant levels of these growth factors were within normal limits or elevated in all but 2 patients (IGFBP-3 only). A positive trend in z-scores was observed in just one of 5 patients for weight and in 2 of 5 for height/length during the follow-up period. Of the 3 patients who experienced negative linear growth velocity over time, 2 had low pretransplant levels of both IGF-1 and IGFBP-3. All patients were weaned from TPN within 3 months after transplant.

Conclusions

Pretransplant levels of growth mediators may be predictive factors in children who will require an intensive regimen of nutritional rehabilitation posttransplant to promote the growth process. Absorption studies may aid in determining the appropriate nutrient substrates for the post-ITx population.     

法舒地尔对早期糖尿病肾脏疾病患者尿结缔组织生长因子和单核细胞趋化因子1的影响

目的 探讨法舒地尔对早期糖尿病肾脏疾病（diabetic kidney disease,DKD）患者尿结缔组织生长因子（connective tissue growth factor,CTGF）、单核细胞趋化因子1（monocyte chemoattracrant protein-1,MCP-1）的影响.方法 采用随机数字表法将82例早期DKD患者分为阳性对照组（贝那普利片10 mg/次,1次/d）和法舒地尔治疗组（贝那普利加法舒地尔注射液60 mg,30 mg/次,2次/d）,每组41例.所有患者严格控制血糖血压.分别于治疗前和治疗后第14天采用酶联免疫吸附法测定尿CTGF、尿MCP 1,采用免疫比浊法测定尿微量白蛋白（micro-albumin,mAlb）,观察2组治疗前和治疗后第14天尿mAlb、CTGF、MCP 1变化,并采用Spearman相关分析分析尿mAlb、CTGF、MCP-1的相关关系.结果 治疗前和治疗后两组间血糖、血压水平差异无统计学意义（P＞0.05）.治疗后阳性对照组和法舒地尔治疗组尿mAlb、CTGF、MCP 1含量均较治疗前下降,差异有统计学意义（P＜0.05）;2组治疗前尿mAlb、CTGF、MCP 1含量比较,差异无统计学意义（P＞0.05）;2组治疗后尿mAlb、CTGF、MCP 1含量比较,差异有统计学意义（P＜0.01）.相关分析显示mAlb含量与CTGF、MCP 1含量呈明显的正相关（P＜0.05）.结论 法舒地尔有独立于肾素血管紧张素系统（Renin-Angiotensin-System,RAS）阻断的肾脏保护作用,其降低早期DKD患者尿蛋白水平的机制可能与降低肾组织CTGF、MCP-1的水平有关.     

不同配方肠外营养对肝硬化大鼠生长激素/胰岛素样生长因子-1轴的影响

目的探讨不同配方肠外营养对肝硬化大鼠肝部分切除术后生长激素/胰岛素样生长因子-1轴的影响。方法正常大鼠作为对照组,肝硬化大鼠随机分为肝硬化术前组,肝硬化肝部分切除术后1 d组,术后行Novamin肠外营养5 d组,术后行Hepa肠外营养5 d组,各组n=6。测大鼠肝功能、血糖及血清GHI、GF-1I、GFBP-3水平,用RT-PCR法检测肝ALBmRNAI、GF-1 mRNA、IG-FBP-3mRNA的表达,肝组织行Ki67免疫组化染色。结果Hepa组肠外营养5 d后血清ALT、ALP、GH分别为(103±23)IU/L(、571±92)IU/L、(1.55±0.12)ng/ml,均比Novamin组明显降低,而血清IGF-1I、GFPB-3分别为(966.4±54.7)ng/ml(、6.9±0.2)ng/ml,均明显升高,肝ALBmRNA、IGF-1mRNAI、GFBP-3mRNA表达水平分别为(1.24±0.06)、(0.85±0.00)、(0.69±0.02),也明显升高,但肝Ki67指数(4.8%±0.3%vs 4.4%±0.4%)却无显著性差异。血清IGF-1I、GFPB-3与血清AST、ALT、ALP水平呈负相关,与血清ALB呈正相关。结论肝硬化大鼠不同配方肠外营养均可反映在生长激素/胰岛素样生长因子-1轴的变化,检测血清IGF-1,IGFBP-3水平有助于营养素的选择。     

The growth hormone-insulin-like growth factor axis in kidney re-revisited.

The use of renal allotransplantation to treat ESRD in the US is limited by lack of organ availability. A possible solution is the transplantation of developing kidneys (metanephric allograft or xenografts). We have conducted studies that demonstrate the feasibility of such a strategy and have shown that IGF I may be useful to accelerate the growth and development of these transplanted organs. The rationale for the use of IGF I in this setting grew from a basic understanding of the role that the growth factor plays in kidney development. ARF in humans is the most costly kidney-related disease requiring hospitalization. Its incidence is increasing. Despite many advances in dialytic therapy, the mortality rate for patients with ARF has not changed in the last several decades. Strategies for treatment of ARF are directed toward supportive care to permit renal regeneration to occur. There exists a need for new therapeutic approaches that can speed recovery and reduce mortality. Although IGF I may not prove to be the 'magic bullet' for ARF, its proposal and testing as a potential therapeutic agent has provided a paradigm for the development of treatment modalities to accelerate renal regeneration based upon a basic understanding of the injury/repair process. The basis for development of a 'growth factor' therapy for ARF will probably evolve, at least in part, out of the testing and use of IGF I in rat models and in humans. The use of GH to treat ESRD was proposed shortly after its isolation and the demonstration of its action in increasing the rate of glomerular filtration. Later, it was discovered that the actions of GH on kidney are mediated by IGF I, and the means by which IGF I enhances glomerular filtration was elucidated. We have shown that humans with ESRD are not resistant to the actions of IGF I in enhancing the GFR, establishing the potential for use of IGF I as a pharmacological agent for ESRD. There is no effective drug therapy to enhance renal function in ESRD. Although much work remains to be done, and clearly caution is advised, our observations establish the potential for the use of IGF I as a therapeutic agent in this setting and justify continued study of IGF I as a medical therapy to delay the need for dialysis.     

Stimulation of growth hormone secretion in children with X-linked hypophosphatemia

X-linked hypophosphatemia is characterized by low serum phosphorus, relative vitamin D deficiency and rickets. Despite adequate metabolic control with oral phosphate and vitamin D therapy, patients with X-linked hypophosphatemia have short stature. Whether growth hormone (GH) deficiency plays a role in short stature in patients with X-linked hypophosphatemia is not known. The purpose of this report was to investigate the response of GH to sequential paired pharmacological stimulation in patients with X-linked hypophosphatemia. Basal GH was 3.8±0.7 ng/ml, insulin-like growth factor-I (IGF-I) was 225±38 ng/ml and IGF binding protein-3 was 3.0±0.2 mg/l in 16 children studied with X-linked hypophosphatemia. In response tol-dopa and arginine hydrochloride stimulation, serum GH rose to above 7 mg/ml in all patients. Thus, the short stature in patients with X-linked hypophosphatemia is not due to a GH/IGF-I secretory defect.     

Serum measurements of testosterone, insulin-like growth factor 1, and insulin-like growth factor binding protein-3 in the diagnosis of prostate cancer among Korean men

Aim： To investigate the relationships of serum testosterone, insulin-like growth factor （IGF）- 1 and IGF-binding protein （IGFBP）-3 levels with prostate cancer risk and also with known prognostic parameters of prostate cancer in Korean men who received radical retropubic prostatectomy （RRP） for clinically-localized prostate cancer. Methods： Serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 were determined in 592 patients who subsequently received prostate biopsy. Results were compared between patients who eventually received RRP for prostate cancer （n = 159） and those who were not diagnosed with prostate cancer from biopsy （control group, n = 433）. Among the prostate cancer only patients, serum hormonal levels obtained were analyzed in relation to serum prostate specific antigen （PSA）, pathological T stage and pathological Gleason score. Results： Prostate cancer patients and the control group demon- strated no significant differences regarding serum levels of total testosterone, free testosterone, IGF-I and IGFBP-3 across the different age groups. Among the cancer only patients, no significant associations were observed for serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 levels with pathological T stage, pathological Oleason score and preoperative PSA. Conclusion： Our data indicate that simple quantifications of serum testosterone and IGF-1 along with IGFBP-3 levels might not provide useful clinical information in the diagnosis of clinically localized prostate cancer in Korean men. Also, our results suggest that serum levels of testosterone, IGF-1 and IGFBP-3 might not be significantly associated with known prognostic factors of clinically localized prostate cancer in Korean men. （Asian J Androl 2008 Mar; 10： 207-213）     

生长激素对大鼠坏死性胰腺炎肠粘膜屏障损害的治疗作用

目的: 研究生长激素(GH)对急性坏死性胰腺炎(ANP)肠粘膜屏障损害的治疗作用. 方法: 逆行胰胆管注射3.5%牛磺胆酸钠诱导ANP模型.试验分4组,即正常(N)组、假手术(SO)组、坏死(ANP)组和治疗(ANP+GH)组.术后24小时抽血测血浆D-乳酸、血清GH、胰岛素样生长因子(IGF-1)和白蛋白浓度,取末端回肠观察绒毛高度和粘膜厚度变化. 结果: ANP组回肠通透性上升,绒毛高度和粘膜厚度减小,血清白蛋白、GH和IGF-1均下降.GH治疗后ANP鼠肠粘膜病理变化减轻,肠道通透性降低,白蛋白和GH浓度提高,而对血清IGF-1影响不大. 结论: 外源性GH可通过升高血清GH和白蛋白来减轻ANP时肠粘膜屏障的损伤.     

内毒素血症状态下生长激素不敏感的实验研究

目的：探讨内毒素血症状态下生长激素不敏感的发生机制。方法：采用雄性SD大鼠（n=180）,静脉分别注射内毒素（LPS）、TNF-α及IL-6,部分注射LPS大鼠同时皮下注射生长激素（GH）,不同时相处死大鼠。应用RT-PCR法测定肝组织胰岛素样生长因子I(IGF I)、生长激素受体（GHR）和细胞因子信号抑制子3（COCS-3）mRNA的表达;应用RIA测定血清GH水平;应用ELISA测定血清TNF-α和IL-6水平。结果：静脉注射LPS后各时相血清GH水平无明显变化,但肝组织IGF I和GHR mRNA的表达却明显下调,最多分别达53％和89％。正常大鼠肝组织SOCS-3mRNA微弱表达,但内毒素血症鼠其表达却明显上调,最高达7.84倍。大剂量LPS注射诱导更多GHRmRNA表达下调和SOCS-3mRNA表达上调。GH可使正常鼠肝组织IGF ImRNA的表达上调25％,但与LPS同时注射则不能阻止IGF I mRNA表达的下调。LPS刺激TNF-α和IL-6的产生,且升高的IL-6水平与SOCS-2mRNA表达上调成高度正相关。静脉注射TNF-α主要使肝组织GHRmRNA表达下调,而IL-6主要使肝组织SOCS-3mRNA表达上调。结论：静脉注射LPS可以诱导生长激素的不敏感,该不敏感可能与GHRmRNA表达下调和SOCS-3mRNA表达上调有关,TNF-α和IL-6可能从不同方面介导了LPS的部分生物效应。     

PPAR-alpha and -gamma agonists attenuate diabetic kidney disease in the apolipoprotein E knockout mouse.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma agonists are widely used in diabetes. In addition to their effects on lipid and glucose homeostasis, these agents have been postulated to have independent renoprotective actions. In the current study, we assess the efficacy of the PPAR-alpha agonist, gemfibrozil, the PPAR-gamma agonist rosiglitazone and the non-thiazolidinedione PPAR-alpha/gamma coagonist, compound 3q, on kidney structure and function in streptozotocin-treated apolipoprotein E knockout mice. METHODS: Control and streptozotocin-diabetic mice were randomized to receive rosiglitazone (20 mg/kg/day), gemfibrozil (100 mg/kg/day), or compound 3q (3 mg/kg/day) by gavage, or no treatment for a period of 20 weeks. Renal fibrosis was assessed by standard histology and collagen IV immunohistochemistry. Kidney function was assessed by urinary albumin excretion and creatinine clearance. RESULTS: Diabetes in this model was associated with an increase in glomerulosclerosis, tubulointerstitial fibrosis and increased collagen IV deposition in the glomeruli and tubules. All three agents significantly attenuated glomerulosclerosis, tubulointerstitial expansion and collagen IV deposition. The increase in albuminuria and the decline in kidney function associated with diabetes in this model were also attenuated by each of these agents, with no superiority observed among various treatment groups. These renoprotective effects were observed in the absence of changes in glucose, insulin or lipid levels or a reduction in blood pressure. CONCLUSIONS: Combined with their independent anti-atherosclerotic actions, and their important effects on dyslipidaemia and insulin resistance, PPAR agonists may be useful for the prevention of diabetic complications, including kidney disease, even in type 1 diabetes.     

Role of insulin and the IGF system in renal hypertrophy in diabetic Psammomys obesus (sand rat).

BACKGROUND: Diabetic nephropathy is caused by multiple factors related to the altered metabolic environment in diabetes mellitus (DM). Experimental diabetic kidney disease is characterized by renal hypertrophy associated with increased tissue concentrations of insulin-like growth factor I (IGF-I). To assess the specific roles of serum insulin and glucose in mediating the development of diabetic nephropathy, the effects of both hyperinsulinaemic and hypoinsulinaemic DM were studied in Psammomys obesus (sand rat), a model of type 2 DM. METHODS: The IGF-I system was studied in normal Psammomys obesus gerbils and at 5, 15 and 70 days after the induction of either hyper- or hypoinsulinaemic DM. To induce hyperinsulinaemic DM, Psammomys were raised on a high-energy diet. Hypoinsulinaemic DM was induced by either administration of streptozotocin or a specially designed diet. RESULTS: Hyperinsulinaemic hyperglycaemic Psammomys did not exhibit renal hypertrophy (unchanged kidney/body-weight ratio) and renal IGF-I levels were in the normal range on days 5, 15 and 70. In contrast, Psammomys with hypoinsulinaemic hyperglycaemia induced either by streptozotocin injection or by pancreas exhaustion brought on by a long-term caloric excess diet, had significant increases in kidney/body-weight ratio which were associated with elevated renal IGF-I and mRNA and protein levels of kidney IGF binding protein I. CONCLUSIONS: This study shows that serum insulin levels in the presence of hyperglycaemia have an important role in the development of experimental diabetic nephropathy in the Psammomys model. The implication of this finding is that the pathophysiological mechanisms for diabetic kidney disease in experimental models may be different for type 1 and type 2 DM.     

Influence of growth hormone and insulin-like growth factor-I on kidney function and kidney growth

Decreased glomerular filtration rate (GFR) in hypopituitarism and increased GFR in acromegaly suggest that growth hormone (GH) has a substantial effect on renal haemodynamics. Extractive and recombinant human (rh) GH in healthy volunteers increased effective renal plasma flow (ERPF) and GFR by 10% and 15% respectively. Renal response to GH was delayed and occurred at the same time as an increase in plasma insulin-like growth factor (IGF)-I values, whereas infusion of rhIGF-I promptly increased GFR and ERPF, indicating that the haemodynamic response of the kidney to GH is mediated by IGF-I. In chronic renal failure (CRF), the acute effect of GH on GFR is obliterated. This might protect the diseased kidney against the undesired consequences of hyperfiltration. Indeed, rhGH treatment for 1 year in children with CRF did not lead to an accelerated decline in GFR compared with the year before treatment. GH and IGF-I also effect renal growth. Exposure to excessive GH in transgenic mice causes renomegaly and progressive glomerular selerosis. In acromegalic humans, increased renal size and weight and increased glomerular diameter are well known, whereas renal failure is not a long-term hazard. At least in normal and hypophysectomized rats treated with doses comparable with the therapeutic regimens used in stunted children, rhGH increased renal weight but in proportion to the increase in body weight indicating an isometric effect of GH on renal growth. From these data, major renal longterm side effects of rhGH treatment in children with CRF appear unlikely.     

氟伐他汀对糖尿病大鼠肾脏转化生长因子β1表达的影响

目的 探讨羟甲基戊二酰辅酶Ａ（ＨＭＧＣｏＡ）还原酶抑制剂氟伐他汀对糖尿病大鼠肾脏转化生长因子表达的影响。方法 将实验动物随机分为正常对照组,糖尿病模型Ｄ组及氟伐他汀治疗组ＤＦ组,第２,８周分别取各组的一半收集标本,检测血糖,血胆固醇,血甘油三酯,血肌酐尿白蛋白及肾脏肥大指标的变化,应用Ｎｏｒｔｈｅｒｎ杂交检测肾皮质中ＴＧＦβ１ｍＲＮＡ表达,免疫组化检测肾内ＴＧＦβ１,纤维连接帽白和ＩＶ型胶原蛋白表     

Effects of short-term recombinant human growth hormone therapy on plasma leptin concentrations in dialysis patients.

BACKGROUND: Hyperleptinaemia is a well-known biochemical feature found in uraemic patients. However, little is known about the hormonal regulation of leptin in chronic renal disease. Recent studies have shown that circulating leptin levels are modified by treatment with recombinant human growth hormone (rhGH), by recombinant insulin-like growth factor I (rhIGF I), or by a combination of rhIGF I plus rhGH in patients with chronic renal failure. We performed a prospective study to assess plasma leptin concentrations in a group of dialysis patients both before and during short-term rhGH therapy. METHODS: We studied eight dialysis patients (four haemodialysis (HD) and four on continuous ambulatory peritoneal dialysis (CAPD); three female, five male; mean age 63.9 +/- 3.1 years). All patients were instructed to maintain a stable diet (35 kcal/kg/day and 1 g protein/kg/day ideal body weight) and were treated with rhGH (0.2 IU/kg/day s.c.) for 4 weeks. Blood samples were taken at 0, 2, 4, and 8 weeks for determination of leptin, GH, and IGF I. Serum insulin concentrations were assessed at 0 and 4 weeks. RESULTS: Mean plasma leptin concentrations were elevated (36.2 +/- 12.8 ng/ml) at study outset and increased progressively throughout the 4 weeks of rhGH therapy (43.7 +/- 13.5 ng/ml (2 weeks, NS) and 70.6 +/- 18.4 ng/ml (4 weeks, P<0.0001)). These values returned to baseline levels (38.0 +/- 12.0 ng/ml, NS) at 1 month after rhGH withdrawal. rhGH therapy was accompanied by the development of direct correlations between leptin and IGF I concentrations at 2 weeks (r=0.86, P<0.01), and with correlations between leptin and IGF I (r=0.84, P<0.01) and between leptin and insulin (r=0.88, P<0.01) after 4 weeks of rhGH administration. CONCLUSION: These results confirm the presence of high circulating plasma leptin in dialysis patients and show that these levels are further increased by exogenous rhGH administration. The increase in plasma leptin after rhGH therapy may be related to the rhGH-induced changes in insulin in these patients.