糖尿病胰岛素受体活性的研究

为阐述胰岛素受体活性测定的临床意义,探讨糖尿病的发病机制,对４７例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）、１７例胰岛素依赖型糖尿病（ＩＤＤＮ）及２８例正常对照者行红细胞胰岛素受体（ＩＲ）测定。结果表明：ＮＩＤＤＭ高亲和力ＩＲ及低亲和力ＩＲ均明显低于配对年龄的正常对照组,尤以尚未治疗的初诊ＮＩＤＤＭ为著,但无高胰岛素血症,表明ＩＲ降低系原发性缺陷,而非降调节机制所致。ＩＤＤＭ高亲和力及低亲和力ＩＲ则明显高于对应的正常对照组。经用外源性胰岛素治疗后,ＩＲ值明显下降,表明ＩＤＤＭ的ＩＲ升高系升调节机制所致,而非原发性ＩＲ缺陷。     

INFLUENCE OF ENDOGENOUS AND EXOGENOUS OESTROGENS ON POSTERIOR PITUITARY SECRETION IN WOMEN

Four normally menstruating subjects were studied throughout the menstrual cycle to investigate changes in plasma LH, arginine vasopressin (AVP), oxytocin (OT) and oxytocin associated neurophysin (NPOT). A clear mid-cycle LH peak was observed in each subject. Mean levels of AVP, OT and NPOT were 2.2 pmol/l, 1.1 pmol/l and 39 pmol/l, respectively. There were no significant differences between plasma levels during follicular, mid-cycle and luteal phases for each of these. Two further subjects with anovulatory cycles were studied in a similar way. In the first subject, with polycystic ovarian disease, posterior pituitary peptide levels were in the normal range, whereas the other subject, recovering from anorexia nervosa, had raised plasma levels of all posterior pituitary peptides (AVP 8.1 pmol/l, OT 1.8 pmol/l, NPOT 131 pmol/l, mean values) despite a normal osmolality. Administration of ethinyl oestradiol, 100 micrograms or 500 micrograms, had no effect of either AVP or OT, but 100 micrograms caused a marked rise in NPOT levels in all cases within 12 h (from mean 64 pmol/l to mean 196 pmol/l) and the levels remained elevated for 3 d.     

EFFECT OF EXOGENOUS INSULIN ON FASTING SERUM LEVELS OF GASTRIC INHIBITORY POLYPEPTIDE (GIP) IN JUVENILE DIABETES

The effect of insulin on fasting levels of immunoreactive gastric inhibitory polypeptide (IR-GIP) has been examined in insulin-dependent, juvenile-type diabetics who were well-controlled with two doses of an intermediate insulin. After withdrawal of the evening insulin injection the fasting blood glucose and serum IR-GIP levels were elevated and decreased significantly following intravenous insulin towards normal values. There was a significant positive correlation between levels of blood glucose and serum IR-GIP before and during insulin application. It is suggested that fasting serum GIP levels increase in case of insulin deficiency because basal GIP secretion is suppressed by normal insulin levels.     

非胰岛素依赖型糖尿病合并冠心病者的胰岛素抵抗

为了解非胰岛素依赖型糖尿病（ＮＩＤＤＭ）病人中胰岛素抵抗与冠心病的关系，对４０例ＮＩＤＤＭ合并冠心病的男病人与３６例未合并冠心病的ＮＩＤＤＭ男病人的血糖、胰岛素、胰岛素敏感性指数（ＩＳＩ）、血脂、载脂蛋白等进行比较，并对其与冠心病的关系进行多因素ｌｏｇｉｓｔｉｃ逐步回归分析，结果显示，ＮＩＤＤＭ病人中的ＩＳＩ与冠心病呈显著负相关（ＯＲ０．２３７，９５％可信区间０．０９０９～０．６１６７，Ｐ＝０．００３２），这种相关独立于年龄、肥胖、血压、血脂等心血管危险因素。提示胰岛素抵抗是非胰岛素依赖型糖尿病病人冠心病发病的独立危险因素。     

BONE DENSITY OF NORMAL WOMEN IN RELATION TO ENDOGENOUS AND EXOGENOUS OESTROGENS

To evaluate the relationship between duration of hormone replacementtherapy (HRT) and forearm bone density, a population-based studyhas been conducted of 4638 women comparing bone density of 1079women who had taken HRT for varying times with those who hadnever taken it. Forearm bone mineral content (BMC) was measuredby single photon absorptiometry. Additionally, free oestradioland sex hormone binding globulin levels were measured in womenwith high and low bone mineral content. There were no detectable differences in BMC in those who tookHRT for up to 24 months compared with those who did not. Thereafterthere were significant positive regression coefficients forduration periods of 2 to 5 yr (ß = 0.77, P = 0.04and ß = 1.76, P = 0.03) and more than 5 yr (ß= 1.66, P<0.0005 and ß = 1.87, P = 0.009) in post-menopausaland oophorectomized women. The major determinants of BMC wereheight, and in post-menopausal or oophorectomized women, age.Weight and parity also had additional explanatory power forpre- and post-menopausal women. Those who were in the highestquintile of BMC but had never taken HRT showed significantlyelevated percentage free oestradiol compared with those in thelowest quintile. Thus HRT is osteoprotective if taken after the menopause formore than 24 months. KEY WORDS: Bone density, Oestrogens, Hormone replacement therapy, Breast cancer, Free oestradiol     

人类白细胞相关抗原HLA DQB1基因与IDDM的关联

利用ＰＣＲ／ＳＳＯ方法对ＩＤＤＭ病人，ＬＡＤＡ病人，ＮＩＤＤＭ病人以及健康对照者进行ＨＬＡ ＤＱＢ１基因分型。结果发现ＤＱＢ１＊０２０１及ＤＱＢ１＊０３０２在ＬＡＤＡ组显著增高，分别为５３．４％，６６．７％比正常组的１９．５％和３４．２％。与正常组相比，ＤＱＢ１＊０３０２在ＩＤＤＭ组显著增高，为９１．１％比３４．２％。     

SPECIFIC INHIBITION OF ALDOSTERONE RESPONSES TO ENDOGENOUS AND EXOGENOUS ANGIOTENSIN II BY SOMATOSTATIN

Aldosterone and renin responses to head-up tilt (60 degrees for 1 h) and angiotensin II infusions (2,5 and 10 ng/kg/min) 1 h later were compared in six normal subjects during infusions of somatostatin (3 micrograms/kg/min) or saline. The infusions were performed on separate days two weeks apart. The increase in aldosterone due to exogenous angiotensin II and orthostasis were significantly attenuated by somatostatin. Neither the increase in plasma renin activity (PRA) nor the angiotensin II mediated suppression of PRA were affected by somatostatin. These findings are consistent with the recent observation that somatostatin suppresses aldosterone release in response to angiotensin II in rat adrenal cells in culture and they indicate a possible role for somatostatin in the regulation of aldosterone secretion.     

THE HALF-LIFE OF ENDOGENOUS INSULIN AND C-PEPTIDE IN MAN ASSESSED BY SOMATOSTATIN SUPPRESSION

The in-vivo half-lives of insulin and C-peptide have been assessed in normal man by a method which examines the decline of endogenously produced insulin and C-peptide after somatostatin suppression of secretion. Venous blood samples were taken each minute from seven normal subjects: i.v. glucose (0.1 g/kg ideal body weight) was given over 1 min to stimulate secretion, followed by a bolus of 250 micrograms of somatostatin-14 and an infusion of a further 250 micrograms somatostatin-14 over the subsequent 30 min. Plasma samples were analysed for C-peptide, glucose and insulin. The initial mono-exponential half-lives over 8 min were 3.9 +/- 0.3 and 10.2 +/- 0.7 min respectively (mean +/- SEM), with subsequent slower declines. Log transformed insulin and C-peptide yielded biphasic declinations which were assessed by a two-pool model. The rate constant of clearance of insulin implied avid uptake, while the kinetics of C-peptide clearance were slower, and irreversible loss might be explained by glomerular filtration alone. The somatostatin suppression method of measuring hormone kinetics could be used for newly described hormones which are not available for in-vivo studies.     

THE EFFECT OF ENDOGENOUS AND EXOGENOUS GONADOTROPHIN-RELEASING HORMONE ON THE PROLACTIN RESPONSE TO TRH

The prolactin response to TRH in a group of patients with Kallmann's syndrome was found to be significantly lower compared to a group of hypergonadotrophic hypogonadal patients. Since levels of testicular products are comparably low in both groups, we hypothesize that high endogenous LHRH production might be associated with an increased prolactin response to TRH. In support of this, we were, indeed, able to establish a positive correlation between the magnitude of the prolactin response to TRH and basal and LHRH-stimulated LH/FSH levels (the latter serving as an index of endogenous LHRH production) in: (1) eugonadal men, (2) men with Kallmann's syndrome, (3) oestrogen-treated agonadal men, (4) men with severely impaired spermatogenesis and, (5) agonadal men. A direct relation between LHRH and the prolactin response to TRH was demonstrated in a group of eugonadal men, the prolactin response to TRH being greater after prolonged LHRH pretreatment. We speculate that an increase of endogenous or exogenous LHRH might be associated with decreased hypothalamic dopamine secretion which could directly increase prolactin synthesis. Indirectly, decreased dopamine secretion could augment the potency of TRH in releasing prolactin.     

CHANGES IN ENDOGENOUS INSULIN SECRETION DURING CHILDHOOD AS EXPRESSED BY PLASMA AND URINARY C-PEPTIDE

Basal fasting values of plasma C-peptide (CP), plasma insulin and 24 h urine CP were determined in 224 normal non-obese subjects of both sexes ranging in age from 1 to 20 years. Analysis of the results by age, pubertal rating, sex and bone age (BA) during childhood showed that mean +/- SD plasma CP levels in both sexes rose from 0.07 +/- 0.08 pmol/ml at the age of 1-2 years to 0.21 +/- 0.11 pmol/ml at 8-10 years. Mean +/- SD plasma insulin levels in both sexes rose from 3.2 +/- 4.3 microU/ml at the age of 1-2 years to 5.9 +/- 4.5 microU/ml at 8-10 years. Mean +/- SD urine CP levels rose from 6.5 +/- 2.8 pmol/mg creatinine per 24 h at the age of 2-8 years to 7.7 +/- 3.5 pmol/mg creatinine per 24 h at 8-11 years in both sexes. During puberty, plasma and urine CP and plasma insulin levels rose further to peak at pubertal stage P3, the values in females being higher (CP = 0.32 +/- 0.06 pmol/ml) than those in males (CP = 0.22 +/- 0.06 pmol/ml) (P less than 0.005). Plasma insulin levels in females were 13.2 +/- 6.9 microU/ml and 6.4 +/- 3.1 microU/ml in males (P less than 0.05). Urine CP levels were 14.5 +/- 5.7 pmol/mg creatinine per 24 h and 10.8 +/- 5.4 pmol/mg creatinine per 24 h in females and males respectively (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

INSULIN EXCESS AS THE INITIAL LESION IN DIABETES

Oral glucose-tolerance tests (G.T.T.s) with serum - immunoreactive - insulin (I.R.I.) measurements were done on a " diabetic " Tamil Indian family, on members of a Cape Coloured population who screened positive on urine and capillary-blood testing, and on controls. The more potentially diabetic a group became, the higher the fasting insulin level and the greater the insulin response, whether this potentiality was indicated by overweight, borderline G.T.T.s, or diabetic parentage, and however the insulin response was expressed. However, when chemical diabetes appeared, the I.R.I. response was reduced and delayed. It is concluded that, with regard to oral glucose stimulation in these two population groups, the earliest biochemical lesion is associated with insulin excess rather than insulin deficiency.     

半合成人胰岛素治疗糖尿病的效果

本文观察到原用国产猪胰岛素治疗的成年糖尿病病人在换用半合成人胰岛素6个月后,日平均胰岛素剂量减少(P=0.09),空腹及餐后2小时血糖较换药前低(P<0.05);对照组均无明显改变。用人胰岛素者约半数病人血清胰岛素抗体逐渐下降;对照组大多继续上升。低血糖反应发生率两组相当。结果表明,人胰岛素的临床效果优于国产猪胰岛素,此与前者的免疫原性较低有密切关系。     

ORCADIAN VARIATION OF GH-INDEPENDENT IGF-BINDING PROTEIN IN DIABETES MELLITUS AND ITS RELATIONSHIP TO INSULIN. A NEW ROLE FOR INSULIN?

Evidence is accumulating that a non-GH dependent insulin-like growth factor-binding protein (IGF-BP) is not only a carrier protein but also has an active role in the growth process. We have measured levels of this IGF-BP, using a specific RIA, over 12 or 24-h periods in 11 adolescents with diabetes mellitus and five normal adults. In each of the normal the IGF-BP was undetectable for most of the day but with a broad nocturnal peak observed, with levels up to 50 micrograms/l. The levels of IGF-BP were unrelated to the secretory pattern for GH but correlated inversely with the concentration of circulating insulin. In the diabetics a very similar pattern was observed, but with detectable levels throughout the day and much higher peak levels seen at night. Peak levels were up to 120 micrograms/l if a long-acting insulin preparation was administered in the evening but were 400-500 micrograms/l if the long-acting preparation was administered in the morning. The IGF-BP was strongly correlated with plasma glucose in this latter group. In a further group of diabetics overnight profiles were obtained on two separate nights, a normal night and a night with euglycaemia maintained with a glucose clamp technique. Euglycaemia failed to affect peak levels of the binding protein, although the shape of the nocturnal peak was altered consistent with the altered pattern of circulating free insulin. In this group a strong inverse correlation was obtained between the IGF-BP and free insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

INSULIN ANTIBODIES IN ÆTIOLOGY OF LABILE DIABETES

The maximum binding capacity and affinity constant of insulin-binding antibodies have been measured in sera of insulin-treated patients attending a diabetic outpatient clinic. The patients were classified as stable (thirteen) or labile (six) on the basis of clinical criteria. The sera of stable patients had moderate amounts of insulin-binding antibodies of low affinity: patients in the labile group had very small amounts of antibody or antibodies which were avid binders of insulin. The avid-binding antibodies were less effective in buffering changes in free-insulin concentration which occur when therapeutic insulin enters the vascular space.     

用改进的最小模型对糖耐量减退和Ⅱ型糖尿病患者胰岛素抵抗致病机制的研究

用改进的最小模型分别对正常人、IGT(糖耐量减退)和NIDDM(II型糖尿病)患者进行胰岛素敏感指数(S_1)、胰岛素自身代谢效能(S_G)及胰岛β细胞功能分析.结果表明:改进的最小模型与标准的最小模型相比较,两种方法对评估S_1和S_G有高度的相关性(S_1·r=0.856,P相似文献   

血糖,血浆胰岛素水平与血压升高的关系发生于糖尿病之前？

对年龄２５岁～７４岁２０１例糖耐量正常（ＮＯＧＴＴ）、３０７例ＩＧＴ、３６６例新发现ＮＩＤＤＭ，进行Ｐｅｒｓｏｎ单相关分析。年龄、性别、ＢＭＩ、空腹及服糖后血糖、胰岛素（ＩＮＳ）水平分别与血压正相关，调整年龄、性别、ＢＭＩ、血浆胆固醇、抽烟等因素后，ＮＯＧＴＴ及ＩＧＴ血糖与血压相关，ＮＩＤＤＭ者血糖与血压不相关，提示血糖水平对血压的影响发生于糖尿病之前。ＮＯＧＴＴ、ＩＧＴ、和ＮＩＤＤＭ总组，ＮＯＧＴＴ及ＩＧＴ组血浆ＩＮＳ水平与血压不相关，只有年龄小于５０岁，非肥胖的ＮＯＧＴＴ者血浆ＩＮＳ水平与血压相关，提示血浆胰岛素水平对血压的影响发生于年轻非肥胖的糖耐量正常者。     

THE HYPERCALCIURIA OF DIABETES MELLITUS: ITS AMELIORATION WITH INSULIN

Calcium and phosphous metabolism was investigated in 20 patients with diabetes mellitus when their diabetes was under poor metabolic control and again once optimal glycaemic control was achieved with aggressive insulin therapy. Ten of the twenty uncontrolled diabetics had hypercalciuria; insulin therapy returned calcium excretion to normal in five. Twenty-four hour calcium excretion fell in all but two patients when optimal diabetic control was achieved and calcium excretion was positively correlated with glucose excretion. Urinary cyclic AMP excretion, which was in the high normal range during poor control, decreased significantly during optimal insulin therapy. These data suggest that the hypercalciuria of uncontrolled diabetes may be a form of renal hypercalciuria which could result in parathyroid stimulation which might contribute to the development of osteopenia in patients with diabetes mellitus.