Relationship between the weight of parathyroid glands and their secretion of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism

Secondary hyperparathyroidism is one of the common and important abnormalities of mineral metabolism in hemodialysis patients. In this study we investigated the relationship between the weight of individual parathyroid glands (PTG) and their secretion of parathyroid hormone (PTH). Sixty-four PTGs in 16 patients undergoing parathyroidectomy (PTx) at our hospital were included in this study. Patients' ages ranged from 34 to 68 years (60.3 +/- 6.6 years). They were undergoing maintenance dialysis therapy for 81-256 months (175.3 +/- 56.0 months). The cause of end-stage renal failure was chronic glomerulonephritis in all patients. We measured whole PTH (wPTH) levels before PTx and 15 min after the resection of each individual gland (Delta whole PTH). A positive correlation was found between the weight of individual gland and ultrasonography (US) size of individual PTG (r = 0.91, P < 0.001, N = 53). A positive correlation was found between the total mass of the gland and the total volume of PTG on US (r = 0.896, P < 0.001, N = 16). A positive correlation was found between the mass of each individual gland and Delta whole PTH (r = 0.625, P < 0.001, N = 64); however, massive PTGs did not secrete more whole PTH per unit mass (0.01 g). Determination of the volume of PTGs by US is a good indicator of their weight. Larger PTGs secrete more whole PTH per gland, whereas these PTGs did not have the ability to secrete more PTH per unit volume.     

Elevated urinary prostaglandin excretion and the effect of indomethacin on renal function in incipient diabetic nephropathy

We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and urinary albumin excretion in incipient diabetic nephropathy (defined as urinary albumin excretion between 30 and 300 mg/24 h (microalbuminuria) in two out of three sterile ketone-free 24-h urine collections in patients having insulin-dependent diabetes mellitus (IDDM) without hypertension or other kidney disease). The urinary excretion of prostaglandin E2 was significantly elevated in 8 insulin-dependent diabetic patients with incipient nephropathy as compared with 9 normoalbuminuric IDDM patients and 11 healthy controls: 317 (182-1273); 95 (67-225); 132 (54-263) pg/min, respectively (2p less than 0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within 2 weeks in 8 females having IDDM with incipient nephropathy. The study design was a randomized double-blind trial with the patients receiving either indomethacin (150 mg/day) or placebo for 3 days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandin E2 excretion (73%) (2p less than 0.01), urinary albumin excretion rate diminished from 207 (63-253) to 87 (49-147) mg/24 h (2p less than 0.01), fractional clearance of albumin declined (70%) (2p less than 0.01). Glomerular filtration rate remained stable (108 (88-133) versus 110 (95-142) ml/min). Blood glucose and blood pressure were comparable during the placebo and indomethacin treatment (12.6 +/- 3 versus 13.4 +/- 5 mmol/l and 122/79 +/- 3/9 versus 122/82 +/- 4/10 mmHg, respectively). Our results suggest that enhanced glomerular synthesis of vasodilating prostaglandins may accelerate microalbuminuria in incipient diabetic nephropathy.     

甲状旁腺激素及其拟似剂治疗骨质疏松症的研究进展

甲状旁腺激素(PTH)目前已作为一种促骨合成药物,用于骨质疏松症的临床治疗。它所发挥的生物学效应取决于其作用模式和剂量,即间断小剂量使用能增加骨形成,而大剂量持续使用则加速骨吸收使骨量减少。PTH对骨代谢调节的确切机制尚未阐明,大量研究工作力图从各个层面寻找PTH治疗骨质疏松的效应模式及机制,以便使其更安全有效地应用于临床,本文对目前的研究进展作综述。     

Production of parathyroid hormone and parathyroid-hormone-related protein by breast cancer cells in culture

Parathyroid-hormone-related protein (PTHrP) has been implicated in the origin of malignant hypercalcaemia. However, PTHrP production is not restricted to neoplastic cells, it is widespread among a variety of normal cell types and tissues. A physiological role for PTHrP has not been well defined. We describe a case of breast cancer with bone metastases and humoral hypercalcaemia of malignancy, with high levels of plasma C-terminal parathyroid hormone (PTH), mid-molecule PTH and PTHrP. Cells from breast cancer biopsies were cultured and medium samples assayed for the C-terminal and mid-molecule fragments, intact PTH and PTHrP. The data indicate a progressive increase in both PTH fragments and PTHrP levels, over a period of 30 days. No temporal parallelism exists between PTH fragments and PTHrP concentrations, the former being maximum at the 14th day, and the latter at the 30th day from the beginning of the culture. Our results indicate a coproduction of PTH and PTHrP by the breast cancer cells both in vivo and in vitro.Abbreviations PTH parathyroid hormone - PTHrP PTH-related protein - HHM humoral hypercalcaemia of malignancy This work was supported by a grant awarded by the Italian National Research Council (CNR): Clinical Applications of Oncology Research (ACRO) no. 92.02170.PF/39     

肝炎肝硬化的骨钙素、甲状旁腺素、降钙素的变化及其临床意义

目的：为了解肝硬化骨病的形成机理。方法：本文采用放射免疫法对３５例肝炎肝硬化的血清进行了骨钙素、甲状旁腺素（ＰＴＨ）及降钙素（Ｃａｌｃｉｔｏｎｉｎ）的测定。结果：肝硬化患者的骨钙素（Ｇａｌ）明显高于正常对照（Ｐ＜０．０１），ＰＴＨ也高于正常，血钙低于正常，但均无统计学意义（Ｐ＜０．０５），各激素与血清白蛋白、凝血酶原时间及总胆红素之间无明显相关。按Ｃｈｉｌｄ分级，Ｃ级患者的Ｇａｌ及ＰＴＨ明显高于Ａ级及Ｂ级患者，而血钙浓度低于Ａ级及Ｂ级。结论：肝硬化对骨病的产生与所测三种激素的代谢紊乱有密切关系，由于钙离子吸收不良所致的低钙血症在致肝硬化骨病中可能起着相当重要的作用     

Effect of hypoxia on parathyroid hormone in lactating and neonatal rats: interaction with halothane

Low oxygen in the blood (hypoxemia) may occur in the neonate or women in the postpartum period. Administration of inhalation anesthetic may be required in this period. The purpose of this study was to evaluate the effect of 7 d of hypoxia on the neonatal rat pup and lactating dam without or with acute halothane anesthesia on serum calcium and calciotropic hormones. Ionized calcium was not altered by hypoxia or halothane administration. Hypoxia from birth had no effect on serum parathyroid hormone (PTH) in 7-d-old rat pups (48±4 pg/mL). Halothane increased PTH in rat pups (74±8 pg/mL). The effect of halothane was not augmented in hypoxic pups. Hypoxia for 7 d had no effect on serum PTH in lactating dams (23±3 pg/mL). Halothane resulted in an increase in PTH (106±17 pg/mL). When halothane was administered to hypoxic lactating dams, a striking increase in serum PTH was observed (401±50 pg/mL). We hypothesize that halothane and hypoxia alter parathyroid gland function by a direct effect on cellular calcium dynamics. This interaction may have clinical significance in hypoxic patients requiring general anesthesia.     

甲状旁腺激素对去卵巢SD大鼠及其成骨细胞基质GLA蛋白表达的影响

目的 观察甲状旁腺激素对去卵巢SD大鼠及其原代成骨细胞基质GLA蛋白(MGP)表达的影响,探讨MGP在绝经后骨质疏松症发病机制中的可能作用.方法 36只SD雌鼠被分为3组,每组12只:假手术组、单纯去卵巢组(OVX组)和去卵巢加甲状旁腺激素干预组(PTH组).PTH组大鼠去卵巢3周后,予甲状旁腺激素(2 μg/kg,每周3次,持续12周).所有大鼠18周后处死.每3周收集尿及血液.观察腰椎组织及骨密度变化,酶联免疫吸附( ELISA)法检测血清及尿液中MGP的量;免疫组化法观察腰椎未羧化MGP的表达,荧光实时定量观察腰椎及成骨细胞MGP mRNA的表达.结果 甲状旁腺激素干预后去卵巢SD大鼠血清及尿液中MGP量,腰椎未羧化MGP表达、MGP mRNA表达与单纯去卵巢组比较差异有显著性(P＜0.05),甲状旁腺激素( 1-34)在10-2mol/L、10-8mol/L、10-9mol/L上调成骨细胞MGPmRNA的表达较空白对照组分别为6.78倍、5.31倍和2.23倍,呈剂量依赖性,差异均有统计学意义(P＜0.05).结论 甲状旁腺激素对MGP基因及蛋白表达的影响可能在绝经后骨质疏松发病机制中发挥重要作用.     

甲状旁腺素受体1表达对高糖状态下INS-1细胞功能影响研究

目的 观察甲状旁腺受体1(PTH1R)的表达对胰岛β细胞胰岛素合成与分泌功能影响.方法 构建出PTH1R基因沉默的细胞模型后,分别应用放射免疫法观察25 mmol/L D-葡萄糖处理后对照组、阴性基因克隆组(siPTH1R-NC)、PTHrP组及阳性基因序列组(siPTH1R)细胞内胰岛素含量、葡萄糖刺激胰岛素分泌能力、应用Fluo-3/AM 检测INS-1细胞内钙离子浓度及应用INS-1细胞2-脱氧-[3H]-葡萄糖摄入率检测INS-1细胞葡萄糖转运能力.结果 PTHrP组胰岛素分泌能力高于其他3组,siPTH1R组则低于对照组及siPTH1R-NC组(均P＜0.01);PTHrP组中细胞内胰岛素含量显著高于对照组、siPTH1R-NC及siPTH1R组(均P＜0.01),其他3组间差异无统计学意义;PTHrP组中钙离子浓度水平高于其他3组,siPTH1R组低于对照组及siPTH1R-NC组.PTHrP组中细胞2-脱氧-[3H]-葡萄糖摄入率高于其他3组.结论 高糖状态下PTH1R表达水平与INS-1细胞胰岛素合成与分泌功能有关,可能为INS-1细胞自我保护的一种作用.

Abstract：

Objective To observe insulin synthesis and secretion in INS-1 under high glucose, and to clarify the effect of PTH1R. Methods After successful construction of recombinant PTH1R-siRNA vectors in INS-1 cell, insulin secretion and intracellular insulin content of control group, siPTH1R-Negative control group, PTHrP group, and siPTH1R group under 25 mmol/L glucose were measured by radioimmunoassay in INS-1 cell. Intracellular calcium were detected by Fluo-3/AM and the capability of glucose transport was calculated by assaying the uptake of [3H]-2-deoxy-D-glucose in cells.Results Compared with control group, and siPTH1R-NC group, PTHrP group showed increased capability of insulin secretion; PTHrP group had higher intracellular insulin levels than others; PTHrP group showed increased intracellular calcium; the uptake of [3H]-2-deoxy-D-glucose under high glucose after 48h of PTHrP group was increased(all P＜0.01). Conclusion There is a close relationship between PTH1R activation and insulin secretion and synthesis, PTH1R activation may be one of the protective mechanisms in maintaining function of β-cell under high glucose.     

Dysfunction of tubular phosphate reabsorption related to glomerular filtration and blood glucose control in diabetic children

Summary The renal handling of inorganic phosphate was studied by measuring the urinary excretion rate of phosphate ( ), phosphate-(Cr⁵¹) EDTA clearance ratio ( ) and maximal tubular reabsorption of phosphate per litre glomerular filtrate ( ) during fasting in 26 ambulatory Type 1 (insulin-dependent) diabetic children without clinical signs of microangiopathy (age: 7–14 years; duration of disease: 3–14 years). Similar measurements were made in 28 healthy schoolchildren (age: 8–14 years). and were significantly enhanced in the diabetic children (p<0.001) and correlated with the degree of hyperglycaemia (p<0.005). was significantly suppressed in the diabetic children (1.23 versus 1.73 mmol/1, p<0.001). This disturbance was neither related to changes in serum parathyroid hormone nor to growth hormone concentrations but was inversely correlated with the degree of hyperglycaemia (r=-0.61, p<0.001) and with tubular reabsorption of glucose in the diabetic subjects, the mean maximal ( ) and absolute tubular phosphate reabsorption rates were equal to those of the 28 healthy subjects. Both in the diabetic and healthy subjects, these parameters were positively correlated with glomerular filtration rate which was significantly elevated in the diabetic children (138 versus 109 ml/min per 1.73 m², p<0.01). The study demonstrates a dysfunction in tubular phosphate reabsorption in diabetic children which is related to glycaemic regulation.     

Effect of glucose and insulin on protein and basement membrane synthesis in isolated glomeruli of diabetic rats

Summary In incubation experiments with isolated glomeruli, an increased synthesis of protein and basement membranes was detected in diabetic rats compared to metabolically healthy controls. Different glucose concentrations in the incubation medium and insulin did not influence protein and basement membrane synthesis of nondiabetic glomeruli. On the other hand, in diabetic glomeruli the synthetic activity depends on glucose concentration. Insulin had a stimulating effect on protein and basement membrane synthesis diminished at lower glucose concentration. The increased synthetic activity demonstrated at higher glucose concentration was not inhibited by insulin. Supported byDeutsche Forschungsgemeinschaft, Bad Godesberg     

Effects of short-term insulin-like growth factor-I or growth hormone treatment on bone turnover, renal phosphate reabsorption and 1,25 dihydroxyvitamin D3 production in healthy man

Objectives. To find out whether insulin-like growth factor-I (IGF-I) mimics the stimulatory effects of growth hormone (GH) on bone turnover and renal tubular phosphate reabsorption. Design. Randomized, crossover study. Setting. University Hospital, Zürich, Switzerland. Subjects. Seven young healthy male subjects. Interventions. Each subject was studied three times at 2-week intervals, treated with saline 0.9% (S), IGF-I [8 μg kg^?1 h^?1] by a continuous subcutaneous infusion and finally with GH (6 U. twice daily s.c.) for 5 days. Main outcome measures. 36 h after the start of treatment, IGF-I, biochemical markers of bone turnover, calcium, calcium regulating hormones, kidney function and phosphate reabsorption were measured in serum and in 2 h urine in fasting state. Results. Serum levels of IGF-I were 26.8±7.3 (S), 119.4±11.4 (IGF-I) (P<0.02) and 58.4±12.9 nmol L^?1 (GH) (P<0.02), respectively. Serum osteocalcin and carboxyterminal propeptide of type I collagen (PICP) as well as the urinary deoxypyridinoline/creatinine and the calcium/creatinine ratios were all significantly higher after IGF-I (P<0.02) or GH (P<0.02) than after saline treatment. PTH levels did not change in response to treatment. Total albumin-corrected calcium increased only after GH treatment (P<0.05). The free calcitriol index rose from 2.2.±0.5×10^?5 (S) to 2.81±0.25×10^?5 (IGF-I) (P<0.03) and 2.45±0.25×10^?5 (GH), respectively. Serum phosphate and maximal tubular reabsorption divided by glomerular filtration rate (TmP/GFR) were significantly raised by GH (P<0.03) but not by IGF-I as compared to saline 0.9%. Conclusions. (i) Similar to GH, IGF-I rapidly activates bone turnover. (ii) IGF-I does not mimic the effect of GH on renal phosphate reabsorption in spite of comparable effects on renal blood flow and glomerular filtration rate. (iii) IGF-I increases free calcitriol index in face of unchanged serum levels of calcium, phosphate and PTH, consistent with a direct stimulatory effect on 25-OHD-1a-hydroxylase.     

Effects of insulin on urinary calcium excretion by diabetic rats in the absence of blood glucose control

Summary Male rats weighing approximately 250 g were given streptozotocin (STZ), 60 mg/kg, i.p., on two successive days. Six h after the last STZ injection, some STZ-diabetic rats began receiving daily injections of insulin (NPH, 1.5 U, s.c.). At various times after the above treatments the following studies were performed: control rats, STZ-diabetic rats and NPH-treated STZ-diabetic rats were injected s.c. with calcium-45 and housed individually in metabolic cages. Urine from each rat was collected at 24 h intervals for two weeks. Volumes, osmolalities, glucose concentrations, total calcium and radioactivity due to calcium-45 were measured. The results of the studies showed that: STZ-diabetes caused rapid urinary excretion of the injected⁴⁵Ca and increased renal excretion of⁴⁰Ca; the increased urinary excretion of calcium was not due to an osmotic effect or to a direct nephrotoxic action of STZ; and insulin therapy instituted early, but insufficient to control blood glucose, significantly reduced the diabetes-induced calcium loss. This study was supported by grant 5 SO7 RRO5386; Biological Research Support Grant Program, NIH and by the American Heart Association, Mississippi Affiliate. Recipient of a scholarship and fellowship from a MARC Undergraduate Research Grant (5-T34-GM7651-06) awarded to Tougaloo College, Jackson, Mississippi.     

Relationship between albuminuric CKD and diabetic retinopathy in a real-world setting of type 2 diabetes: Findings from No blind study

Background and aimsRecently, the albuminocentric view of diabetic kidney disease (DKD) in type 2 diabetes (T2DM) has been changing. Therefore, the relationship between diabetic retinopathy (DR) and chronic kidney disease (CKD) has to be addressed according to this new clinical presentation of DKD. The aim of this study was to evaluate, in a real-world setting, the correlation DR–DKD in T2DM.Methods and resultsA total of 2068 type 2 diabetic patients enrolled in a multicenter cross-sectional study were investigated. Albuminuric subjects were largely prevalent among subjects with DR (p = 0.019). In the whole study population, no difference in albumin excretion rate (AER) was observed between presence/absence of DR; instead, AER was significantly higher among patients with glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² (CKD) (p = 0.009), above all in those with CKD and AER ≥0.03 g/24 h (p = 0.005). Multivariate analysis confirmed that eGFR (O.R. 0.976; 95% C.I.: 0.960–1.028; p < 0.001) and AER (O.R. 1.249; 95% C.I. 1.001–1.619; p = 0.004) were independently associated with DR and HDL–cholesterol (O.R.: 1.042; 95% C.I.: 1.011–1.120; p = 0.014). Additionally, among patients with eGFR <60 mL/min/1.73 m² and albuminuria, both eGFR and AER significantly varied between those with/without DR (p = 0.012 and p = 0.005, respectively), and this finding was observed among only albuminuric patients. Analogous results were obtained considering DR classification. AER was significantly higher among subjects with either proliferative DR (PDR) or severe nonproliferative DR (NPDR), with regard to mild NPDR (0.498 and 0.938 g/die vs. 0.101 g/die; p < 0.001, respectively). Similar results were obtained in the specular subgroups.ConclusionIn T2DM with DKD, the AER seems to be related to the presence of DR. This association is confirmed above all in those with more severe DR.     

ACE2对糖尿病大鼠肾小球足细胞的影响及厄贝沙坦干预作用的研究

目的 探讨糖尿病大鼠肾组织局部血管紧张素转换酶(ACE)2对肾小球足细胞的影响及厄贝沙坦的干预作用.方法 56只Wistar大鼠经链脲佐菌素诱导糖尿病模型,死亡9只,其余随机分为糖尿病组(n=11)、30 mg/(kg·d)肼屈嗪干预组(n=9)、25 mg/(kg·d)厄贝沙坦干预组(n=9)、50 mg/(kg·d)厄贝沙坦干预组(n=9)、200 mg/(kg·d)厄贝沙坦干预组(n=9),同时设正常对照组(n=7).于造模后第4周开始予肼屈嗪、厄贝沙坦干预,第12周观察24h尿微量白蛋白排泄率(UAER),采用免疫组化技术检测肾组织ACE2的分布和表达情况,免疫组化SP法检测肾小球WT1表达情况,Image.Pro Plus 6.0彩色图像分析系统半定量检测足细胞密度.结果 正常对照组UAER低于糖尿病组和药物干预组[包括肼屈嗪干预组、25 mg/(kg·d)厄贝沙坦干预组、50 mg/(kg·d)厄贝沙坦干预组、200 mg/(kg·d)厄贝沙坦干预组](P＜0.001);药物干预组UAER低于糖尿病组(P＜0.001);所有厄贝沙坦干预组UAER较肼屈嗪干预组显著降低(P ＜0.05);50 mg/(kg·d)厄贝沙坦干预组、200 mg/(kg·d)厄贝沙坦干预组UAER较25 mg/(kg·d)厄贝沙坦干预组明显降低(P＜0.001).肾组织ACE2表达与肾小球足细胞密度呈正相关(r=0.381,P＜0.001),糖尿病组ACE2表达较正常对照组明显降低(P＜0.05),而所有厄贝沙坦干预组显著高于糖尿病组和肼屈嗪干预组(P ＜0.001),厄贝沙坦干预组、肼屈嗪干预组足细胞密度显著高于糖尿病组(P ＜0.001);200 mg/(kg·d)厄贝沙坦干预组高于肼屈嗪干预组、25 mg/(kg·d)厄贝沙坦干预组、50 mg/(kg·d)厄贝沙坦干预组、糖尿病组.结论 肾组织ACE2减少可导致足细胞密度降低,进而引起肾脏损害;而厄贝沙坦可上调肾组织ACE2的表达,增加足细胞密度,发挥降压外的肾脏保护作用,且呈现剂量依赖性.     

Irreversible loss of normal beta-cell regulation by glucose in neonatally streptozotocin diabetic rats

Summary Animals with NIDDM display abnormal glucose regulation of insulin secretion and biosynthesis. We tested reversibility of abnormal regulation by normoglycaemia using an islet transplantation technique. Inbred non-diabetic and neonatally STZ diabetic rats (n-STZ) were used. Transplantations insufficient to normalize the blood glucose levels (200 islets under kidney capsule) were performed from diabetic to normal (D-N) and from diabetic to diabetic (D-D), as well as from normal to normal (N-N) and from normal to diabetic (N-D) rats. Four weeks after transplantation, graft bearing kidneys were isolated and perfused with Krebs-Henseleit bicarbonate buffer to measure insulin secretion in response to 27.8 mmol/l glucose and 10 mmol/l arginine. Four weeks of normoglycaemia failed to restore glucose-induced insulin secretion from n-STZ islets (glucose induced increment:-1.7±2.5 fmol/min in D-N, 1.2±7.1 fmol/min in D-D). In contrast to normal islets, normoglycaemia reduced insulin mRNA contents (60±24 in D-N, 496±119 in D-D; O.D.-arbitrary units). However, arginine-induced secretion was markedly enhanced by diabetic environment in both normal and n-STZ islet grafts. These results indicate that selected aspects of glucose recognition are irreversibly damaged by a long-term diabetic state or, alternatively, by a lasting effect of STZ administration.Abbreviations NIDDM non-insulin-dependent diabetes mellitus - STZ streptozotocin - O.D. optical density - IRI immunoreactive insulin     

The role of glucose and insulin in the metabolic regulation of growth hormone secretion

The exact physiological basis for the suppression of growth hormone secretion by oral glucose intake remains unknown, despite the widespread use of the oral glucose tolerance test in endocrinology. Lack of growth hormone suppression by glucose occurs in about a third of patients with acromegaly, as well as in other disorders. It is currently known that the secretion of growth hormone is affected by various factors, such as age, gender, body mass index, and the redistribution of adipose tissue. There is also evidence of the impact of overeating as well as being overweight on the secretion of growth hormone. It is known that both of these conditions are associated with hyperinsulinemia, which determines the possibility of its predominant role in suppressing the secretion of growth hormone. The purpose of this review is to discuss the accumulated data on the isolated effects of hyperglycemia and hyperinsulinemia on growth hormone secretion, as well as other metabolic regulators and conditions affecting its signaling. Understanding of the pathophysiological basis of these mechanisms is essential for further research of the role of glucose and insulin in the metabolic regulation of growth hormone secretion. However, the studies in animal models are complicated by interspecific differences in the response of growth hormone to glucose loading, and the only possible available model in healthy people may be the hyperinsulinemic euglycemic clamp.     

The effect of dimethylbiguanide on glucose tolerance,serum insulin and growth hormone in obese patients

Zusammenfassung An 16 adipösen Patienten wurden der Glucoseassimilationskoeffizientk _G sowie die radio-immunologisch meßbaren Serumspiegel von Insulin und Wachstumshormon während einer intravenösen Glucosebelastung 1. vor, 2. nach einer Woche und 3. nach 10 Wochen peroraler Behandlung mit 2 × 850 mg Dimethyl-biguanid bestimmt. - Die Patienten wurden nach dem ursprünglichenk _G Wert in 3 Gruppen eingeteilt: Gruppe 1: 7 Patienten,k _G > 1.3. Gruppe 2: 7 Patienten,k _G < 1.3. Gruppe 3: 2 Patienten mit manifestem Diabetes mellitus. — In Gruppe 1 ergab sich keine signifikante Änderung des Mittelwertes vonk _G durch die Biguanidtherapie, die ursprüngliche Hyperinsulinämie nahm nach einer Woche auf die Hälfte ab. In Gruppe 2 kam es nach einer Woche zu einem signifikanten Anstieg von k_G, die Insulinspiegel zeigten hier ein unterschiedliches Verhalten: Bei 4 Patienten wurde eine Senkung, bei 3 Patienten eine Erhöhung beobachtet. In Gruppe 3 fand sich nach einer Woche eine Senkung der Nüchternblutzuckerspiegel sowie eine Senkung der reaktiven Insulinspiegel in der Spätphase. Nach Absetzen des Medikamentes nach 10 Wochen waren in allen 3 Gruppen keine signifikanten Veränderungen gegenüber den Ausgangswerten nachweisbar. Die Mittelwerte der Wachstumshormonspiegel, die insgesamt unter 5 ng/ml blieben, ließen insbesondere in Gruppe 2 eine Abnahme unter Biguanidtherapie erkennen. Auffallend waren zeitliche Veränderungen der Sekretionsdynamik des Insulins, meist im Sinne einer Normalisierung; in 3 Fällen kam es jedoch zu einer Verschiebung des reaktiven Maximums in die Spätphase. — Die Untersuchungen zeigten, daß bei übergewichtigen Patienten ohne manifesten Diabetes mellitus eine gestörte intravenöse Glucosetoleranz durch Dimethylbiguanid normalisiert wird und daß bei Adipösen die Insulin- und Wachstumshormonspiegel meist im Sinne einer Normalisierung beeinflußt werden, wenn auch bei einzelnen Patienten ein gegensätzliches Verhalten gefunden wurde. Es ergaben sich Hinweise dafür, daß die Veränderungen der Insulinspiegel nicht immer allein durch eine periphere Biguanidwirkung verursacht sein dürften. Es ließ sich kein sicherer Langzeiteffekt von Dimethylbiguanid nachweisen, vielmehr erwies sich die aktuelle Konzentration des Pharmakons als stoffwechselwirksam.

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Effet du diméthylbiguanide sur la tolérance au glucose, l'insuline du sérum et l'hormone de croissance chez des malades obèses

Résumé Le coefficient d'assimilation du glucose (k_G), les taux sériques d'insuline immunoréactive (IRI) et l'hormone de croissance (GH) ont été déterminés à l'occasion d'une charge de glucose par voie intra-veineuse chez 16 malades obèses avant traitement, après traitement oral d'une semaine au diméthylbiguanide et après traitement de 10 semaines. -Les malades ont été groupés selon leurs valeurs k_G initiales: groupe 1: 7 malades, k_G > 1.3. -groupe 2: 7 malades, k_G < 1.3. -groupe 3: 2 malades avec diabète établi. -Dans le groupe 1, les valeurs k_G moyennes n'ont montré aucun changement significatif à la suite du traitement au biguanide, tandis que l'hyperinsulinémie initiale était réduite de moitié au

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Presented at the 5th Annual Meeting of the Deutsche Diabetesgesellsehaft, Bonn-Bad Godesberg, May 1970.     

Effects of antibody to renal plasma membrane on urinary excretion of adenosine 3',5'-monophosphate and phosphate induced by parathyroid hormone infusion in rats

Studies were made on the effects of pretreatment of rats with antibody to renal cortical plasma membrane (anti-RPM) on the urinary excretion of cAMP and phosphate induced by infusion of parathyroid hormone (PTH). With PTH infusion, the increase in the urinary excretion of cAMP and phosphate were not parallel. Infusion of 1-40 mg anti-RPM inhibited PTH-induced increase in urinary phosphate excretion but not the increase in urinary cAMP. Infusion of 100 mg of anti-RPM inhibited PTH-induced increases in the excretion of both substances. Infusion of nonimmunized rabbit immunoglobulin (IgG; normal IgG) did not affect PTH-induced increases in the excretion of either cAMP or phosphate. In vitro in isolated renal tubules, with 10 mg/ml anti-RPM, the increases in cAMP content induced by PTH were significantly less than those seen with lower concentrations of this antibody or with normal IgG.