A correlational study between serum asymmetric dimethylarginine level and impaired glucose tolerance patients associated with obesity

Asymmetric dimethylarginine (ADMA) plays a vital role in the regulation of insulin sensitivity and has been shown as a potential marker for various disease, including type 2 diabetes mellitus (DM2). However, the correlation between ADMA and impaired glucose tolerance (IGT) and obesity has not been studied. A total of 195 subjects were involved in our study. The characteristics of the subjects in the study cohort were measured and analyzed. We found that the serum ADMA and C-reactive protein levels were significantly increased in IGT and diabetic patients, whereas the levels of lipoprotein A and adiponectin were decreased, especially in diabetic patients with obesity. The serum ADMA level was positively correlated to a homeostatic model assessment for insulin resistance, and multivariate regression analysis further indicated that ADMA was an independent factor for DM patients with obesity. Our study expands the understanding of the complicated relationship between obesity, insulin resistance, IGT, and ADMA. In addition, we demonstrated that the serum ADMA level could serve as a diagnositic biomarker of the early signs for IGT patients with obesity.     

Hyperinsulinism and insulin resistance in the polycystic ovary syndrome as tested with tolbutamide

The aim of this research was to study both insulin secretion and insulin resistance index (IRI) in seventeen females, aged 16-30, affected by polycystic ovarian syndrome. The diagnosis was made using clinical, hormonal, radiological and echographic criteria. Eight healthy women, carefully matched with our patients for age and for statistical obesity incidence, were studied as controls. Both glycemic and insulinemic curves, areas, insulinemic/glycemic area ratio (IRI) were studied by tolbutamide test (1 g i.v.). Areas were assessed by planimeter, blood glucose by Trinder method, blood insulin by a RIA method, statistical study by t Student test and correlation coefficients. These latter were determined by comparing individual plasma testosterone, FSH, LH and LH/FSH ratio values together with urinary total 17-ketosteroid and delta HEA output values on the one hand and insulin areas and IRI values on the other. Increased glycemic areas, insulinemic peaks and areas, associated with markedly increased IRI values, were observed in the patients. A correlation exists between hyperinsulinism, insulin resistance on the one hand and increased urinary androgens output on the other. delta HEA resulted particularly increased over other androgenic fractions.     

Hormonal Regulation of Lipid Metabolism in Healthy Subjects with or without Obesity

Parameters of insulin resistance and lipid transport were studied in nonobese subjects and in obese subjects with different body fat distribution, and the results were compared with current concepts of the physiological and biochemical mechanisms of abdominal (android) and gluteofemoral (gynoid) types of obesity, concomitant dyslipoproteinemias, and the roles of insulin and insulin resistance in these conditions. Disturbances of the hormonal regulation of lipid metabolism, which manifest themselves as hyperinsulinemia, insulin resistance, and a decreased serum level of the insulin antagonist somatotropin, were associated only with abdominal obesity and were considered to be one of the main causes of atherogenic dyslipoproteinemia in this type of obesity.     

Decrease of plasma somatotropin levels following thyroliberin (TRH) administration in patients with hyperthyroidism.

Thyroliberin was observed to induce a significant decrease of plasma somatotropin levels in patients with untreated hyperthyroidism, except those with very low initial somatotropin levels. These data have confirmed our previous finding where we noted that under the conditions of thyroid hormone excess thyroliberin was able to exert an inhibitory effect on somatotropin release.     

Maternal treatment with somatotropin during early gestation affects basic events of myogenesis in pigs

The effects of maternal treatment with somatotropin during early gestation on fetal muscle development were determined. Crossbred gilts received daily injections of either 3 ml of a placebo ( n=31) or of 6 mg porcine somatotropin ( n=31) from day (d) 10 to 27 of gestation and samples were collected from d 28 embryos, d 37 and 62 fetuses, and from neonates. Administration of somatotropin increased the total number of fibres (primary and secondary fibres) in neonatal semitendinosus muscle of middle- and low-weight littermates, whilst no increase was observed in psoas major muscle. Somatotropin induced increases in muscular protein concentration, creatine kinase activity, muscle fibre girth, as well as type II to type I fibre conversion which revealed an advanced degree of differentiation at birth. Treatment effects on prenatal development preceded these changes. Increased DNA concentrations at d 28 of gestation indicate stimulation of cellular proliferation during the embryonic stages. Thereafter, the withdrawal of somatotropin caused a transient delay of differentiation as indicated by lower protein concentrations and creatine kinase activity compared with controls at d 37 of gestation. This was compensated again at d 62, and the number of semitendinosus primary fibres was increased in middle-weight fetuses, whereas secondary or total fibre number did not yet differ. However, enhanced expression of Myf5 and MyoD indicates higher numbers of initially determined, proliferating myoblasts that may have contributed to increased formation of secondary fibres. In conclusion, maternal somatotropin is an influential factor in early pregnancy capable of affecting the basic events of myogenesis.     

An investigation of sites that bind human somatotropin (growth hormone) in the liver of the pregnant rabbit.

The binding of 125I-labelled human somatotropin (growth hormone) to a crude membrane preparation from the liver of pregnant rabbit, and to receptors solubilized from this fraction by Triton X-100, was dependent on time, temperature and receptor concentration. At 4 degrees C a steady state was reached after 20 h, and maximum specific binding (as a percentage of total tracer added) was approx. 50% for both membrane-bound and solubilized receptors. Solubilization did not significantly affect the binding properties of the receptor at low concentrations of Triton X-100 (less than 0.05%, v/v, in the assay tube). However, at higher concentrations (approx. 0.1%, v/v), the detergent lowered the ability of some hormones, for example ovine prolactin, to displace 125I-labelled human somatotropin, but did not affect other hormones such as bovine somatotropin. Some somatogenic hormones, such as bovine somatotropin, and some lactogenic hormones, such as ovine prolactin, displaced 125I-labelled human somatotropin from membrane-bound and solubilized receptor preparations. Furthermore, 85% of 125I-labelled bovine somatotropin was displaced from membrane-bound receptors by ovine prolactin, and 125I-labelled ovine prolactin was almost completely displaced by bovine somatotropin. Scatchard analysis of the binding data for human somatotropin suggested a single class of binding sites in the membrane-bound receptor preparation, with an affinity (Ka) of 1.9 X 10(9) M-1 and a capacity of 1726 fmol/mg of protein; these values were slightly increased by solubilization (Ka = 3.2 X 10(9) M-1, capacity = 2103 fmol/mg of protein). Scatchard analysis of binding to membrane-bound receptors also indicated a single class of high-affinity binding sites for bovine somatotropin (Ka = 4.8 X 10(9) M-1, capacity = 769 fmol/mg) and for ovine prolactin (Ka = 6.1 X 10(9) M-1, capacity = 187 fmol/mg).     

A novel concatenated dimer of recombinant bovine somatotropin

A novel protein concatenated dimer structure was generated during the folding/oxidation of inclusion bodies of recombinant bovine somatotropin synthesized inEscherichia coli. The structure of this dimeric molecule was determined by peptide mapping with trypsin, and limited proteolysis by thrombin. Peptide mapping demonstrated that the two disulfide pairs in bovine somatotropin dimer were identical to those in monomer. Limited proteolysis with thrombin resulted in the cleavage of only a single peptide bond between arginine-132 and alanine-133 in bovine somatotropin dimer. This single peptide bond cleavage was sufficient to convert this dimer to a monomeric molecular weight species as analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and HPLC. Since the single cleaved peptide bond is present in the large disulfide loop of bovine somatotropin, these data demonstrate that the dimeric molecule exists as a novel concatenated structure through the interlocking of the disulfide loops of this protein.     

Effect of somatotropin on the activity of mitochondrial alpha-glycerophosphate dehydrogenase in the liver of rats with hypo- and hyperthyroidism

The activity of mitochondrial alpha-glycerophosphate dehydrogenase in the liver of rats with hypothyrosis (two weeks after total thyroidectomy) is 36% of the normal level; in rats with hyperthyrosis (three weeks after subcutaneous implantation 2 mg of l-thyroxin on a kaolin base) it is 7.4 times as high. Bovine somatotropin (0.5 mg per 100 g of body mass) injected subcutaneously for 10 days has no effect on the enzyme activity in intact rats and in rats with hypothyrosis. In animals with hyperthyrosis somatotropin produces a 37% decrease in the enhance activity of the enzyme. Somatotropin fully normalizes a 25% increased amount of protein in the liver mitochondrial fractions of rats with hyperthyrosis.     

Changes of plasma insulin, urea, amino acids and rumen metabolites in somatotropin treated dairy cows

Summary An experiment was performed to evaluate the effects of somatotropin on plasma free amino acid, urea and insulin concentrations and rumen fermentation pattern and to assess their relationships. Four Italian Friesian dairy cows fitted with rumen cannulae were used in a switch-back design. Slow releasing recombinant bovine somatotropin (640 mg/cow) was injected every 28 days for two consecutive periods. Rumen fluid and blood samples were collected before and after feeding at 0, 7 and 21 days after rbST injection. Exogenous rbST increased plasma insulin concentration and the insulin response to feeding, and decreased plasma urea and free essential and branched chain amino acid concentrations. rbST did not affect rumen fermentation pattern. No correlation was found between rumen and plasma parameters measured after feeding. Our results are consistent with the notion that the main effect of somatotropin is post-absorptive.     

腹型肥胖对急性冠脉综合征患者冠状动脉病变严重程度的影响

目的:研究腹型肥胖对急性冠脉综合征(ACS)患者冠状动脉病变严重程度的影响。方法:选择2012年4月至2013年4月在我院接受治疗的ACS患者120例,根据腰围身高比(RWH)将患者分为无腹型肥胖者60例(对照组,RWH0.5)及腹型肥胖者60例(观察组,RWH0.5)。测量所有患者的基本参数,计算RWH,利用冠脉造影判断冠脉病变的支数和程度,根据Gensini评分法对冠脉造影结果进行评价,分析冠脉病变范围、Gensini积分和RWH的相关性。结果:观察组的收缩压(SBP)、空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)及Gensini积分水平均显著高于对照组,差异均有统计学意义(均P0.05)。观察组的高密度脂蛋白(HDL-C)水平显著低于对照组,差异有统计学意义(P0.05)。双支病变的RWH及Gensini积分水平显著高于单支病变,三支病变的RWH及Gensini积分水平显著高于单支病变及双支病变,差异均有统计学意义(均P0.05)。根据Spearman法分析相关性可知,冠脉病变范围、Gensini积分和RWH均呈正相关(r=0.635,0.739;P=0.000,0.000)。结论:ACS患者RWH水平增高与冠脉病变的严重程度关系密切,有效控制腹型肥胖对于降低心血管类疾病发病率以及降低冠脉病变的程度具有重要意义。     

Regional fat deposition in the legs is useful as a presumptive marker of antiatherogenesity in Japanese

To examine the pathological role of regional fat deposition in development of metabolic and cardiovascular disorders, regional fat distribution was evaluated using metabolites and hormones as measures of obesity-related disorders. The subjects enrolled were 100 sex-matched inpatients, who were admitted, regardless of their body mass index values, for further examination of unusual results from periodic medical screening tests, and for examination of obesity-induced complications and treatment of obesity. Body fat distribution was analyzed using dual energy X-ray absorptiometry (DEXA). Analysis of parameters regarding fat distribution showed that gender was one of the determinants affecting correlation between fat distribution and metabolites of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (TC), or triglyceride (TG). However, regardless of gender, both leg trunk fat (L/Tr) and arm trunk fat (A/Tr) ratios negatively correlated with a total body fat (% total fat) ratio, whereas the intercept value of female regression line in L/Tr was greater than that in males, but not in A/Tr. Percentage total fat, L/Tr, and A/Tr in males correlated significantly with FPG, TC, TG, low-density lipoprotein (LDL), very low density lipoprotein (VLDL), atherogenic index (A.I.), and apoB/A1 only low density lipoprotein (LDL) was significantly correlated solely to L/Tr and A/Tr. These results indicate that regional fat distribution in males may not be a major determinant for development of metabolic disorders in obese patients. Unlike male regional fat distribution, female L/Tr correlated significantly not only with TC, TG, and LDL, but also with FPG and HbA1c, although both of the latter 2 glucose-related parameters in males showed no correlation with any parameters of fat deposition. The remaining female parameters of fasting plasma insulin, VLDL, A.I., and ApoB/A1 correlated with each of the three parameters of fat deposition, as similarly shown in males. The powerful and negative correlation was thus evident, particularly in females, between leg fat deposition and parameters of glucose and lipid metabolites. The resulting information provides a novel insight that regional fat deposition at the legs is useful as a marker for metabolic and cardiovascular disorders associated with obesity.     

Natural peptides and their analogs. XXXV. Synthesis and properties of [Ala5, Orn9]somatostatin

A total chemical synthesis of [Ala5, Orn9]somatostatin has been performed. This structural analogue of natural somatostatin inhibits the release of somatotropin, insulin and glucagon, but shows no inhibitory effect on secretion of prolactin.     

肥胖合并高脂血症患者血清食欲素A、25-羟维生素D3、瘦素水平与胰岛素抵抗、脂代谢紊乱和肥胖评价指标的相关性分析

摘要 目的：探讨肥胖合并高脂血症患者血清食欲素A（orexin A）、25-羟维生素D3[25-(OH)D3]、瘦素（Leptin）水平与胰岛素抵抗、脂代谢紊乱和肥胖评价指标的相关性。方法：选择2019年2月至2021年12月中国医科大学附属第四医院收治的105例肥胖合并高脂血症患者为研究组,另取同期在中国医科大学附属第四医院健康体检的73例志愿者为对照组。检测并对比两组血清orexin A、25-(OH)D3、Leptin、胰岛素抵抗相关指标、脂代谢指标及肥胖评价指标水平的差异。采用Pearson相关性分析血清orexin A、25-(OH)D3、Leptin水平与胰岛素抵抗相关指标、脂代谢指标及肥胖评价指标的相关性。结果：研究组血清orexin A、25-(OH)D3水平低于对照组,而Leptin水平高于对照组（P＜0.05）。研究组空腹血糖（FPG）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）水平均高于对照组（P＜0.05）。研究组总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）水平高于对照组,而高密度脂蛋白胆固醇（HDL-C）水平低于对照组（P＜0.05）。研究组体质量指数（BMI）、腰臀比、腰高比均高于对照组（P＜0.05）。肥胖合并高脂血症患者的血清orexin A、25-(OH)D3水平与FPG、FINS、HOMA-IR、TC、TG、LDL-C水平、BMI、腰臀比、腰高比均呈负相关,与HDL-C水平呈正相关（P＜0.05）;Leptin水平与FPG、FINS、HOMA-IR、TC、TG、LDL-C水平、BMI、腰臀比、腰高比均呈正相关,与HDL-C水平呈负相关（P＜0.05）。结论：肥胖合并高脂血症患者血清orexin A、25-(OH)D3水平降低,Leptin水平升高,且与胰岛素抵抗、脂代谢紊乱及肥胖指标升高有关。     

Primary structure of cyanogen bromide fragments of sei whale (Balaenoptera borealis) pituitary somatotropin]

5 fragments are isolated after the degradation of somatotropin from sei whale pituitary glands with cyanogen bromide: N-terminal 4-segmented; C-terminal 12-segmented with the internal disulfide bond; middle 25- and 30-segmented and a high molecular weight fragment following N-terminal tetrapeptide and bound with disulfide bond to 30-segmented fragment. Complete amino acid sequence of three shortest cyanogen bromide fragments is deciphered and N- and C-terminal sequence is investigated in two large fragments after their uncoupling under performic acid oxidation. Amino acid sequence is deciphered of a peptide obtained after trypsine hydrolysis of 30-segmented cyanogen bromide fragment. Comparison of amino acid sequence of whale somatotropin fragments with that of sheep, beef and human somatotropin has revealed that 57 out of 61 identified amino acid residues of whale somatotropin repeat amino acid residues in similar regions of beef somatotropin, 56--of sheep and only 42--of human somatotropins. Besdies, 4 of 5 revealed amino acid substitutions in whale hormone, as compared with sheep somatotropin, are amino acids which are present at the same positions in human hormone.     

Purification and characterization of pituitary bovine somatotropin

Bovine somatotropin (bST) has been isolated from pituitary glands and compared in a variety of chemical analyses and bioassays with somatotropin derived from recombinant Escherichia coli. Comparison of pituitary extracts and purified bST by Western blot analysis of two-dimensional gels suggested that the immunoreactive somatotropin species present in the extract were also present in the purified material, with no significant losses or degradation as a result of the purification method. NH2-terminal sequence analysis indicated the presence of equal quantities of Ala-Phe-Pro-Ala-Met-Ser-Leu-Ser- and Phe-Pro-Ala-Met-Ser-Leu-Ser- sequences. The Met-Ser-Leu-Ser-NH2-terminal sequence, a degradation product observed in NIH standard lots, was not detected. Assay of bioactivity in a bovine liver receptor-binding assay and in a female rat growth assay showed pituitary bST and recombinant methionyl-bovine somatotropin to be equipotent. Tryptic maps and sequence analysis of pituitary-derived somatotropin suggest the presence of isoaspartate derivatization at Asp128.     

Inflammation associated with obesity: relationship with blood and bone marrow endothelial cells

The purpose of this study was to assess the inflammatory nature of obesity and its effect on blood and bone marrow endothelial cell populations. Obese patients (BMI ≥30) had significantly higher concentrations of the inflammatory marker C-reactive protein (CRP) (P = 0.03) and lower concentrations of the anti-inflammatory cytokine interleukin-10 (IL-10) (P = 0.05). This cytokine profile is consistent with obesity being an inflammatory condition and is further supported by the significant correlation between total white blood cell count and BMI (r = 0.15; P = 0.035). High BMI was associated with significantly lower numbers of early endothelial cells (CD45(-)/CD34(+)) in the bone marrow (r = -0.20; P = 0.0068). There was also a significant inverse correlation between BMI and a more mature endothelial cell phenotype (CD45(-)/31(+)) in the blood (r = -0.17; P = 0.02). In addition, there was a significant correlation between BMI- and endothelial-related cells of hematopoietic origin (CD133(+)/VEGFR-2(+)) in the bone marrow (r = -0.26; P = 0.0007). Patients with higher plasma IL-10 and insulin-like growth factor (IGF) concentrations had higher numbers of endothelial phenotypes in the bone marrow suggesting a protective effect of these anti-inflammatory cytokines. In conclusion, this work confirms the inflammatory nature of obesity and is the first to report that obesity is associated with reduced endothelial cell numbers in the bone marrow of humans. These effects of obesity may be a potential mechanism for impaired tissue repair in obese patients.     

Preparation of highly purified human somatotropin (growth hormone)

A method for preparation of highly purified human somatotropin on large-scale basis is described. Starting from deep-frozen pituitary gland, less time is needed to obtain highly purified hormone than with other published methods for preparation of human somatotropin. The hormone obtained in this fasion is chromatographically and electrophoretically homogeneous; it shows high biological and radioimmunological growth hormone activity and is free of other pituitary hormone activities. The effects of various experimental conditions upon aggregation of somatotropin are critically evaluated.     

Biosynthesis of somatotropin in a recombinant strain of Escherichia coli

A recombinant Escherichia coli K-12 strain was grown in the regime of chemostat with glucose limitation at a different flow rate and in the regime of turbidostat. The stability of its population and the dynamics of somatotropin biosynthesis were studied. The plasmid-containing strain became less stable as the flow rate in the fermenter dropped down, which was due, apparently, to a greater limitation. The level of somatotropin biosynthesis was higher at a low dilution rate (D = 0.075, 0.17 and 0.34 h-1). Possible factors responsible for this phenomenon are discussed.     

Obesity Research in Canada: Literature Overview of the Last 3 Decades

Objective: To identify research published on obesity in Canada, to explore the range of areas studied, and to identify gaps and areas that merit future research attention. Research Methods and Procedures: Medline and International Pharmaceutical Abstracts databases were searched from 1970 onwards. Original articles were identified and categorized by areas of interest. Results: A total of 1186 relevant articles were identified: 17, 136, 687, and 346 articles during the 1970s, 1980s, 1990s, and 2000 to 2003, respectively. Of the articles, 816 were considered original studies and accepted for this analysis. Twelve research areas were identified: basic science involving animal experiments (29%), human experiments (16%), populations surveys (14%), obesity‐related comorbidities (13%), diagnostic/surgical issues (11%), nonpharmacological approaches (7%), drug‐related issues (4%), anthropometrics (2%), impact of weight loss (2%), cost/healthcare use (1%), attitudes/perceptions (0.9%), and models/procedures (0.5%). Two‐thirds of all research was conducted in Quebec (34%) and Ontario (33%). Discussion: Given the multifactorial nature of obesity, Canadian obesity research covers a broad range of areas with a predominance of basic science but lesser emphasis on community and primary care studies. Furthermore, there was a paucity of research on either clinical management of medical conditions in obese patients or clinical aspects that go beyond weight loss. Thus, although Canada appears well represented in basic research, more attention to exploration of clinical issues and healthcare delivery for obese patients appears warranted.